Photoactivatable dye compounds for conjugate formation and methods of making and using the same

Abstract

Disclosed herein are compounds and biomolecule-compound conjugates comprising a photoactivatable silicon-phthalocyanine dye core and having unique linker groups that facilitate binding the photoactivatable silicon-phthalocyanine dye core biomolecule-binding moieties. In some aspects, the linker groups can be attached to beta-positions of the compounds and also can be varied in length, which can facilitate improving therapeutic activity of the compounds or biomolecule-compound conjugates and / or can increase yields associated with methods for making the compounds. Also disclosed are methods of making and using the compounds and biomolecule-compound conjugates described herein.

Description

4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025PHOTOACTIVATABLE DYE COMPOUNDS FOR CONJUGATE FORMATION ANDMETHODS OF MAKING AND USING THE SAMECROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of and priority to the earlier filing date of U.S. Provisional Patent Application No. 63 / 690,585, filed on September 4, 2024, the entirety of which is incorporated herein by reference.ACKNOWLEDGMENT OF GOVERNMENT SUPPORT

[0002] This invention was made with government support under project number ZIA BC 011513 awarded by the National Institutes of Health, National Cancer institute. The government has certain rights in the invention.FIELD

[0003] The present disclosure is directed to photoactivatable silicon-phthalocyanine dye compounds and conjugates comprising such compounds, the compounds comprising unique linkers and substitution patterns and that are useful in various biological applications.BACKGROUND

[0004] Cancer remains a main cause of human death. Although there are several therapies for cancer, there remains a need for therapies that effectively kill the tumor cells while not harming non-cancerous cells. To minimize the side effects of conventional cancer therapies (such as surgery, radiation and chemotherapy), molecular targeted cancer therapies have been developed. Among the existing targeted therapies, monoclonal antibodies (MAb) therapy has the longest history, and to date, over 25 therapeutic MAbs have been approved by the Food and Drug Administration (FDA). Effective MAb therapy traditionally depends on three mechanisms: antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and receptor blockade and requires multiple high doses of the MAb. MAbs have also been used at lower doses as vectors to deliver therapies such as radionuclides or chemical or biological toxins. Ultimately, however, dose limiting toxicity relates to the biodistribution and catabolism of the antibody conjugates.

[0005] Near-infrared photoimmunotherapy (Nl R-PIT) is a method of treating cancers that uses activation of an antibody- photoabsorber conjugate activated by near-infrared light to kill cells. The antibody binds to the appropriate cell surface antigen and a photo-activatable compound induces lethal damage to cell membrane after Nl R- light exposure. Nl R- light4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 exposure induces highly selective, necrotic cancer cell death within minutes without damage to adjoining cells. NIR-PIT appears to specifically kill target cells while leaving adjacent normal cells unharmed.

[0006] Infectious diseases are another class of diseases that contribute to a high number of human deaths. The ability to target and kill (or remove) pathogens remains another field where intensive research has taken place. For example, with antibiotic resistance increasing throughout the world, it is important to identify new mechanisms for targeting and killing harmful bacterial pathogens.

[0007] There exists a need in the art for new compounds that can be used in cancer treatments and / or pathogen treatment / removal, particularly those that can be used in photobased activation mechanisms, like NIR-PIT.SUMMARY

[0008] Disclosed herein are compounds having a structure according to Formula I or Formula II as described herein, wherein: X is a biomolecule-binding moiety or a precursor thereto; the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m- (CR2)p[O(CR2)t]q-{X}, wherein {Core} represents attachment to the phthalocyanine core and {X} represents attachment to X; each R, independently for each occurrence, is selected from hydrogen, halogen, aliphatic, heteroaliphatic, or aromatic; (ii) -CH=CH-[Q1]S-, wherein s is 1 or 0 and Q1is selected from aromatic or -C(=O)Y’- or -S(=O)aY’, wherein Y’ is NR” or O, wherein R” is H, -CN, CF3, or a sulfonyl group; or (ill) -C^C-Q2, wherein Q2is - (CH2)UC(=O)Y’-, wherein u is an integer selected from 1 to 10, Y’ is NR” or O, wherein R” is H, -CN, CF3, or a sulfonyl group; Z is a heteroatom; m is 1 or 0; each of n, p, and t independently is selected from an integer ranging from 0 to 50; and q is an integer selected from 0 to 50; G, if present, is selected from halogen or Linker-X, wherein the linker group and the X group are as defined above: each of R1a, R2a, R33, R1b, R2b, and RSbindependently is selected from hydrogen, aliphatic, halogen, heteroaliphatic, aromatic, thiol, hydroxyl, or amine: or (i) R13and R1bjoin together, with the carbon atoms to which they are attached, to form a 6-membered aromatic ring, (ii) R2aand R2bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring, (iil) R3aand R3bjoin together, with the carbon atoms to which they are attached, to form a si.x-membered aromatic ring, or (iv) any combination of two or more of (i)-(iii); and L is selected from -(CH2)r , -Si(R5)2(CH2)r-, -C(=O)(CH2)r, or -Ph(CH2)r-, wherein each R5independently is aliphatic or aryl, r is an integer selected from 1 to 5 and wherein any CH2 group of the L group is attached to the quaternary amine of Formula I or Formula II.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0009] Also disclosed is a conjugate formed by coupling a biomolecule with a compound according to any or all of the aspects described herein, wherein the biomolecule becomes bound to the compound upon reaction between a functional group of the biomolecule and the X group of the compound.

[0010] Also disclosed is a method for treating a subject or sample using NIR-PIT, the method comprising: administering a compound according to any or all compound aspects, or a conjugate according to any or all conjugate aspects, or a pharmaceutically acceptable composition thereof, to the subject or the sample: and irradiating the conjugate by application of light to a targeted portion of the subject or the sample.

[0011] Also disclosed herein is a method of making a compound according to any or all of the above aspects, comprising: converting a phthalocyanine core precursor having a structure according to Formula III to the compound by performing a click chemistry reaction or a palladium-catalyzed carbon-carbon cross coupling reaction; wherein Formula III is as described herein and R4is selected from halogen or a group having a structure according to a formula {Core}-(CR2)n-CFG, wherein CFG is a clickable functional group and “{Core}” represents attachment of R4to the phthalocyanine core precursor.

[0012] The foregoing and other objects, features, and advantages of the present disclosure will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 shows combined UV-Vis spectra for compound precursors comprising silicon-based phthalocyanine cores, including dimerized compounds (precursors without linker groups labeled as Xdyel , Xdye-2, and Xdye-3) and compound precursors including styrene-based linker group fragments (labeled as Xdye-4 and Xdye-5).

[0014] FIG. 2 shows images of cells that have been treated with IR700 (bottom left image) as a comparative example and a biomolecule-compound conjugate according to the present disclosure, namely p-Tz IR700C10SE bound to cetuximab.

[0015] FIG. 3 shows images of cells that have been treated with IR700 (top row) as a comparative example and biomolecule-compound conjugates according to the present disclosure, including compounds p-Tz IR700C3SE, p-Tz IR700C6SE, and p-Tz IR700C10SE (each bound to cetuximab).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0016] FIG. 4 is a bar graph showing results for cell viability using biomolecule-compound conjugates according to the present disclosure, namely compounds p-Tz IR700G3SE, p-Tz IR700C6SE, p-Tz IR700C10SE, and p-Tz-IR700PEG6SE (each bound to cetuximab), in comparison with IR700 and a control sample without any IR700 or biomolecule-compound conjugates.

[0017] FIG. 5 shows images of cells that have been treated with IR700 (top row) as a comparative example and various biomolecule-compound conjugates according to the present disclosure, namely a-TzEt- 1 R700C8SE, p-TzEt-IR700C8SE, p-alkyne-IR7Q0C7SE, and p-Tz-IR700PEG6SE (each bound to cetuximab).

[0018] FIG. 6 is a bar graph showing results for cell viability using compounds according to the present disclosure, namely p-TzEt-IR700C8SE, and a-TzEt-IR700C8SE (each bound to cetuximab) in comparison with IR700.

[0019] FIG. 7 shows images of cells that have been treated with IR700 (top row) as a comparative example and a biomolecule-compound conjugate, namely IR700-alkene-SE, bound to cetuximab.

[0020] FIG. 8 is a bar graph showing results for cell survival rate after exposing cells to a biomolecule-compound conjugate according to the present disclosure, namely p-Tz- IR700C10SE-alk (bound to cetuximab and referred to as TzlR700-alk in FIG, 8) in comparison with results for IR700.

[0021] FIG. 9 is a bar graph showing results for cell survival rate after exposing cells to a biomolecule-compound conjugate according to the present disclosure, namely p-Tz-naph- IR700C10SE (bound to cetuximab and referred to as Tz-naph-IR700 in FIG. 9) in comparison with results for IR700.

[0022] FIG. 10 is a bar graph showing results for ceil survival rate after exposing cells to biomolecule-compound conjugates according to the present disclosure, namely p-l-Tz- IR700C10SE, p-CI-Tz-IR700C10SE, and p-Br-Tz-IR700C10SE (bound to cetuximab and referred to as CI-TzlR700, Br-TzlR700, and l-TzlR700 in FIG. 10) in comparison with results for lR700.

[0023] FIG. 11 is a bar graph showing results for cell survival rate after exposing cells to a biomolecule-compound conjugate according to the present disclosure, namely p-diTz- IR700C10SE (bound to cetuximab and referred to as diTzlR700 in FIG. 11) in comparison with results for IR700.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0024] FIG. 12 is a bar graph showing results for ceil survival rate after exposing cells to biomolecule-compound conjugates according to the present disclosure, namely p-Tz- IR700C10SE-diEtSi, p-Tz-IR700C1 OSE-diPrSi, and p-Tz-IR700C10SE-diPhSi (bound to cetuximab and referred to as TzlR700-diEtSi, TzlR700-di / PrSi, and TzlR700-diPhSi in FIG. 12) in comparison with results for IR700.

[0025] FIG. 13 is a graph showing normalized cell viability after exposing cells tc biomolecule-compound conjugates according to the present disclosure, namely IR700- alkene-SE, IR700-SA-SE, IR700-Amd-SE, and IR700-PEG-SE (bound to cetuximab and referred to as IR700-alkene, IR700-SA, IR700-Amd, and IR700-PEG in FIG. 13) in comparison with results for IR700.

[0026] FIG. 14 is a graph summarizing results obtained after exposing compounds according to the present disclosure, namely Pyr-IR700 C6 COOH, Styrl-IR700 C6-COOH, IR700-alkene-COOH, IR700-PEG-COOH, IR700-SA-COOH, IR700-Amd-PEG-COOH, to photolysis conditions, along with a comparison of results obtained using IR700.

[0027] FIG. 15 shows images of cells that have been treated with IR700 (top row) as a comparative example and a biomolecule-compound conjugate, namely IR700-PEG-SE, bound to cetuximab.DETAILED DESCRIPTION

[0028] Overview of Terms

[0029] The following explanations of terms and / or symbols are provided to better describe the present disclosure and to guide those of ordinary skill in the art in the practice of the present disclosure. The singular forms “a,” “an,” and “the” refer to one or more than one, unless the context clearly dictates otherwise. The term “or” refers to a single element of stated alternative elements or a combination of two or more elements, unless the context clearly indicates otherwise. As used herein, “comprises” means “includes.” Thus, “comprising A or B,” means “including A, B, or A and B,” without excluding additional elements. All references, including patents and patent applications cited herein, are incorporated by reference.

[0030] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, percentages, temperatures, times, and so forth, as used in the specification ar claims are to be understood as being modified by the term “about.” Accordingly, unless otherwise indicated, implicitly or explicitly, the numerical parameters set4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 forth are approximations that may depend on the desired properties sought and / or limits of detection under standard test conditions / methods. When directly and explicitly distinguishing aspects of the disclosure from discussed prior art, the aspect numbers are not approximates unless the word “about" is expressly recited.

[0031] Unless explained otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0032] “Substituted," when used to modify a specified group or moiety, means that at least one, and perhaps two or more, hydrogen atoms of the specified group or moiety is independently replaced with the same or different substituent groups. In a particular embodiment, a group, moiety, or substituent may be substituted or unsubstituted, unless expressly defined as either “unsubstituted" or “substituted." Accordingly, any of the functional groups specified herein may be unsubstituted or substituted unless the context indicates otherwise or a particular structural formula precludes substitution. In particular aspects, a substituent may or may not be expressly defined as substituted but is still contemplated to be optionally substituted. For example, an “aliphatic" or a “cyclic" moiety may be unsubstituted or substituted, but an “unsubstituted aliphatic” or an “unsubstituted cyclic” is not substituted. In one embodiment, a group that is substituted has at least one substituent up to the number of substituents possible for a particular moiety, such as 1 substituent, 2 substituents, 3 substituents, or 4 substituents. As used herein, the term “substituted” refers to all subsequent modifiers in a term, for example in the term “substituted aliphatic-aromatic," substitution may occur on the “aliphatic” portion, the “aromatic" portion or both portions of the aliphatic-aromatic group. Any functional group disclosed herein can be substituted or unsubstituted, unless otherwise indicated herein.

[0033] A person of ordinary skill in the art will appreciate that compounds may exhibit the phenomena of tautomerism, conformational isomerism, geometric isomerism, and / or optical isomerism. For example, certain disclosed compounds can include one or more chiral centers and / or double bonds and as a consequence can exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), enantiomers, diastereomers, and mixtures thereof, such as racemic mixtures. As another example, certain disclosed compounds can exist in several tautomeric forms, including the enol form, the keto form, and mixtures thereof. As the various compound names, formulae and compound drawings within the- o -4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 specification and claims can represent only one of the possible tautomeric, conformational isomeric, optical isomeric, or geometric isomeric forms, a person of ordinary skill in the art will appreciate that the disclosed compounds encompass any tautomeric, conformational isomeric, optical isomeric, and / or geometric isomeric forms of the compounds described herein, as well as mixtures of these various different isomeric forms. Mixtures of different isomeric forms, including mixtures of enantiomers and / or stereoisomers, can be separated to provide each separate enantiomers and / or stereoisomer using techniques known to those of ordinary skill in the art, particularly with the benefit of the present disclosure. In cases of limited rotation, e.g. around an amide bond or between two directly attached rings such as pyridinyl rings, biphenyl groups, and the like, atropisomers are also possible and are also specifically included in the compounds disclosed herein.

[0034] In any aspects, any or all hydrogens present in the compound, or in a particular group or moiety within the compound, may be replaced by a deuterium or a tritium. Thus, a recitation of alkyl includes deuterated alkyl, where from one to the maximum number of hydrogens present may be replaced by deuterium. For example, methyl refers to both CH3or CHs wherein from 1 to 3 hydrogens are replaced by deuterium, such as in CDxHs-z.

[0035] Certain functional group terms used herein include a symbol which is used to show haw the defined functional group attaches to, or within, the compound to which it is bound. Also, a dashed bondas used in certain formulas described herein indicates an "optional” bond to a substituent or atom of the formula other than hydrogen in the sense that the bond (and in some aspects, the substituent) may or may not be present. In any formulas comprising a dashed bond, if the optional bond and / or any corresponding substituent is not present, then the valency requirements of any atom(s) bound thereto is completed by a bond to a hydrogen atom.

[0036] The symbolis used to indicate a bond disconnection in abbreviated structures / formulas provided herein. A person of ordinary skill in the art recognizes that the definitions provided below and the compounds and formulas included herein are not intended to include impermissible substitution patterns (e.g., methyl substituted with 5 different groups, and the like). Such impermissible substitution patterns are easily recognized by a person of ordinary skill in the art. In formulas and compounds disclosed herein, a hydrogen atom is present and completes any formal valency requirements (but may not necessarily be illustrated) wherever a functional group or other atom is not illustrated. For example, a phenyl ring that is drawncomprises a hydrogen atom attached to each carbon atom of the phenyl ring other than the “a” carbon, even though such4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 hydrogen atoms are not illustrated. Any functional group disclosed herein and / or defined above can be substituted or unsubstituted, unless otherwise indicated herein.

[0037] To facilitate review of the various aspects of the disclosure, the following explanations of specific terms are provided.

[0038] Activated Ester: A functional group that is susceptible to nucleophilic attack. In some aspects of the disclosure, activation can be imparted by modifying an acyl or alkoxyportion of a normal ester, such as by adding electronegative substituents. In exemplary aspects of the disclosure, an activated ester can comprise a carboxyl group attached to a succinimide via the oxygen bound by a single bond to the carbonyl carbon of the carboxyl group.

[0039] Administration: To provide or give a subject an agent, such as a compound or biomolecule-compound conjugate disclosed herein, by any effective route. Exemplary routes of administration include, but are not limited to, topical, injection (such as subcutaneous, intramuscular, intradermal, intraperitoneal, intratumoral, and intravenous), oral, ocular, sublingual, rectal, transderrnal, intranasal, vaginal and inhalation routes.

[0040] Aldehyde: -C(O)H.

[0041] Aliphatic: A hydrocarbon group having at least one carbon atom to 50 carbon atoms (C1-50), such as one to 25 carbon atoms (Ci 25), or one to ten carbon atoms (CMO), and which includes alkanes (or alkyl), alkenes (or alkenyl), alkynes (or alkynyl), including cyclic versions thereof, and further including straight- and branched-chain arrangements, and all stereo and position isomers as well. Aliphatic groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroailphatic, aromatic, or an organic functional group.

[0042] Aliphatic-aromatic: An aromatic group that is or can be coupled to a compound disclosed herein, wherein the aromatic group is or becomes coupled through an aliphatic group. Aliphatic-aromatic groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroailphatic, aromatic, or an organic functional group.

[0043] Aliphatic-aryi: An aryl group that is or can be coupled to a compound disclosed herein, wherein the aryl group is or becomes coupled through an aliphatic group. Aliphatic- aryl groups may be substituted with one or more groups other than hydrogen, such as4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0044] Ahphatic-heteroaryi: A heteroaryl group that is or can be coupled to a compound disclosed herein, wherein the heteroaryl group is or becomes coupled through an aliphatic group. Aliphatic-heteroaryl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0045] Alkenyl: An unsaturated monovalent hydrocarbon having at least two carbon atom to 50 carbon atoms (C2-50), such as two io 25 carbon atoms (€225), or two to ten carbon atoms (C2- 10), and at least one carbon-carbon double bond, wherein the unsaturated monovalent hydrocarbon can be derived from removing one hydrogen atom from one carbon atom of a parent alkene. An alkenyl group can be branched, straight-chain, cyclic (e.g., cycloalkenyl), c / s, or trans (e.g., E or Z). Alkenyl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0046] Alkoxy: -O-aliphatic, such as -O-alkyl, -O-alkenyl, -O-alkynyl; with exemplary aspects including, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, Fbutoxy, sec-butoxy, n-pentoxy (wherein any of the aliphatic components of such groups can comprise no double or triple bonds, or can comprise one or more double and / or triple bonds). Alkoxy groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0047] Alkyl: A saturated monovalent hydrocarbon having at least one carbon atom to 50 carbon atoms (C1-50), such as one to 25 carbon atoms (C ior one to ten carbon atoms (Ci w), wherein the saturated monovalent hydrocarbon can be derived from removing one hydrogen atom from one carbon atom of a parent compound (e.g., alkane). An alkyl group can be branched, straight-chain, or cyclic (e.g., cycloalkyl). Alkyl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0048] Alkynyl: An unsaturated monovalent hydrocarbon having at least two carbon atom to 50 carbon atoms (C2.50), such as two to 25 carbon atoms (C2-25), or two to ten carbon atoms (C2-10), and at least one carbon-carbon triple bond, wherein the unsaturated monovalent hydrocarbon can be derived from removing one hydrogen atom from one carbon4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 atom of a parent alkyne. An alkynyl group can be branched, straight-chain, or cyclic {e.g., cycloalkynyl). Alkenyl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0049] Amide: -C(0)NRbRcor -NRbC(O)Rcwherein each of Rband R° independently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group and can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0050] Amino: -NRbRc, wherein each of Rband Rcindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group, and can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0051] Antibody: A polypeptide ligand comprising at least a light chain or heavy chain immunoglobulin variable region which specifically recognizes and binds an epitope of an antigen, such as a tumor-specific protein. Antibodies are composed of a heavy and a light chain, each of which has a variable region, termed the variable heavy (VH) region and the variable light (VL) region. Together, the VH region and the VLregion are responsible for binding the antigen recognized by the antibody.

[0052] Antibodies include intact immunoglobulins and the variants and portions of antibodies well known in the art, such as Fab fragments, Fab' fragments, F(ab)T fragments, single chain Fv proteins (“scFv”), and disulfide stabilized Fv proteins (“dsFv”). A scFv protein is a fusion protein in which a light chain variable region of an immunoglobulin and a heavy chain variable region of an immunoglobulin are bound by a linker, while in dsFvs, the chains have been mutated to introduce a disulfide bond to stabilize the association of the chains. The term also includes genetically engineered forms such as chimeric antibodies (for example, humanized murine antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, IL); Kuby, J., Immunology, 3rdEd., W. H. Freeman & Co., New York, 1997

[0053] Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (A.) and4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 kappa (K). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE.

[0054] Each heavy and light chain contains a constant region and a variable region (the regions are also known as “domains”). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a "framework" region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs.” The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of immunological Interest, U.S. Department of Health and Human Services, 1991 , which is hereby incorporated by reference). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species, such as humans. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space.

[0055] The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1 , CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VHCDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a Vi CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. Antibodies with different specificities (i.e. different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved In antigen binding. These positions within the CDRs are called specificity determining residues (SDRs).

[0056] References to “VH” or “VH" refer to the variable region of an immunoglobulin heavy chain, including that of an Fv, scFv, dsFv or Fab. References to “VL” or “VL” refer to the variable region of an immunoglobulin light chain, including that of an Fv, scFv, dsFv or Fab.

[0057] A “monoclonal antibody” is an antibody produced by a single clone of B lymphocytes or by a cell into which the light and heavy chain genes of a single antibody have been transfected. Monoclonal antibodies are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma cells with immune spleen cells. Monoclonal antibodies include humanized monoclonal antibodies.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0058] A “chimeric antibody” has framework residues from one species, such as human, and CDRs (which generally confer antigen binding) from another species, such as a murine antibody that specifically binds mesothelin.

[0059] A "humanized" immunoglobulin is an immunoglobulin including a human framework region and one or more CDRs from a non-human (for example a mouse, rat, or synthetic) immunoglobulin. The non-human immunoglobulin providing the CDRs is termed a “donor,” and the human immunoglobulin providing the framework is termed an “acceptor,” In one embodiment, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they must be substantially identical to human immunoglobulin constant regions, / .a, at least about 85- 90%, such as about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDRs, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A “humanized antibody” is an antibody comprising a humanized light chain and a humanized heavy chain immunoglobulin. A humanized antibody binds to the same antigen as the donor antibody that provides the CDRs. The acceptor framework of a humanized immunoglobulin or antibody may have a limited number of substitutions by amino acids taken from the donor framework. Humanized or other monoclonal antibodies can have additional conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. Humanized immunoglobulins can be constructed by means of genetic engineering (see for example, U.S. Patent No. 5,585,089).

[0060] A “human” antibody (also called a “fully human” antibody) is an antibody that includes human framework regions and ail of the CDRs from a human immunoglobulin. In one example, the framework and the CDRs are from the same originating human heavy and / or light chain ammo acid sequence. However, frameworks from one human antibody can be engineered to include CDRs from a different human antibody. All parts of a human immunoglobulin are substantially identical to corresponding parts of natural human immunoglobulin sequences.

[0061] Antigen (Ag): A compound, composition, or substance that can stimulate the production of antibodies or a T cell response in an animal, including compositions (such as one that includes a tumor-specific protein) that are injected or absorbed into an animal. An antigen reacts with the products of specific humoral or cellular immunity, including those induced by heterologous antigens, such as the disclosed antigens. "Epitope" or "antigenic determinant" refers ta the region of an antigen to which B and / or T cells respond. In one embodiment, T cells respond to the epitope, when the epitope is presented in conjunction4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 with an MHC molecule. Epitopes can be formed both from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous ammo acids are typically retained on exposure to denaturing solvents whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, and more usually, at least 5, about 9, or about 8-10 amino acids in a unique spatial conformation. Methods of determining spatial conformation of epitopes include, for example, x-ray crystallography and nuclear magnetic resonance.

[0062] Examples of antigens include, but are not limited to, peptides, lipids, polysaccharides, and nucleic acids containing antigenic determinants, such as those recognized by an immune cell. In some examples, an antigen includes a tumor-specific peptide (such as one found on the surface of a cancer cell) or immunogenic fragment thereof.

[0063] Aromatic: A cyclic, conjugated group or moiety of, unless specified otherwise, from 5 to 15 ring atoms helving a single ring (e.g., phenyl) or multiple condensed rings in which at least one ring is aromatic (e.g., naphthyl, indolyi, or pyrazolopyridinyl) ; that is, at least one ring, and optionally multiple condensed rings, have a continuous, delocalized TT-electron system. Typically, the number of out of plane n-electrons corresponds to the Huckel rule (4n + 2). The point of attachment to the parent structure typically is through an aromatic portion of the condensed ring system. For example,. However, in certain examples, context or express disclosure may indicate that the point of attachment is through a non-aromatic portion of the condensed ring system. For example,. An aromatic group or moiety may comprise only carbon atoms in the ring, such as in an aryl group or moiety, or it may comprise one or more ring carbon atoms and one or more ring heteroatoms comprising a lone pair of electrons (e.g. S, O, N, P, or Si), such as in a heteroaryl group or moiety. Aromatic groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0064] Aroxy: -O-aromatic. Aroxy groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0065] Ary!: An aromatic carbocyclic group comprising at least five carbon atoms, and in some aspects having at least five carbon atoms to 15 carbon atoms (C5-Ci5), such as five to ten carbon atoms (C5-C10), having a single ring or multiple condensed rings, which condensed rings can or may not be aromatic provided that the point of attachment to a remaining position of the compounds disclosed herein is through an atom of the aromatic carbocyclic group. Aryl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0066] Azo: -N=NRawherein Rais hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Azo groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0067] Biomolecule: An organic molecule that can include, in non-limiting aspects, proteins, carbohydrates, lipids, nucleic acids, peptide, antibodies, metabolites, and the like.

[0068] Biomolecuie-Compound Conjugate: A conjugate structure that comprises a biomolecule conjugated to a photosensitive silicon phthalocyanine dye compound according to the present disclosure via a linker group as described herein.

[0069] Cancer: A malignant tumor characterized by abnormal or uncontrolled cell growth. Other features often associated with cancer include metastasis, interference with the norma! functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels and suppression or aggravation of inflammatory or immunological response, invasion of surrounding or distant tissues or organs, such as lymph nodes, etc. “Metastatic disease” refers to cancer cells that have left the original tumor site and migrate to other parts of the body for example via the bloodstream or lymph system. In one example, the cell killed by the disclosed methods is a cancer cell.

[0070] Carbamate: -OC(O)NRbRc, wherein each of Rband R° independently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Carbamate groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0071] Carbonate: -OC(O)ORa, wherein Rais selected from aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Carbonate groups can be substituted with one or more groups other than hydrogen, such as aliphatic,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. In independent aspects, Racan be hydrogen.

[0072] Carboxy!: -C(O)OH.

[0073] Carboxylate: -C(Q)Q or salts thereof, wherein the negative charge of the carboxylate group may be balanced with an M+counterion, wherein M+may be an alkali ion, such as KT, Na’, Li’; an ammonium ion, such as ‘N(RB),< where RBis H, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, or aromatic: or an alkaline earth ion, such as [Ca2’]0.5, [Mg2’]05, or [Ba2f]0.5.

[0074] Click Chemistry: Chemical synthetic methods for forming covalent bonds using compounds that can be joined together using efficient reagent conditions and that can be performed in benign solvents or solvents that can be removed or extracted using facile methods, such as evaporation, extraction, or distillation.

[0075] Clickable Functional Group: A functional group that can be used in click, chemistry to form covalent bonds between (i) two moieties that, when reacted, provide a linker group as described in Formulas of the present disclosure; or (ii) a compound of the present disclosure and a clickable functional group-labeled antibody or a pathogen-targeting compound, such as a bacteria-specific protein.

[0076] Contacting: Placement in direct physical association, including both a solid and liquid form. Contacting can occur in vitro, for example, with isolated cells (e.g., tumor cells), and / or pathogens (e.g., bacterial pathogens); or, in vivo by administering to a subject (such as a subject with a tumor or pathogen),

[0077] Covalent Bond: A chemical bond that involves sharing electrons to form electron pairs between atoms and can include sigma or pi bonds.

[0078] Cyano: -CN.

[0079] Decrease: To reduce the quality, amount, or strength of something. In one example, a therapeutic composition that includes a compound or biomolecule-compound conjugate according to the present disclosure decreases the viability of (i) cells to which an biomolecule-compound conjugate specifically binds, or (ii) a pathogenic target targeted by a compound of the disclosure, following irradiation of the cells or pathogen with light (for example, near-infrared light at a wavelength ranging from 650 nm to 1 100 nm) at a dose of at least 1 J cm2, for example as compared to the response in the absence of the compound or biomolecule-compound conjugate. In some examples such a decrease is evidenced by4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the killing of the cells and / or pathogenic species. In some examples, the decrease in the viability is at least 20%, at least 50%, at least 75%, or even at least 90%, relative to the viability observed with a composition that does not include a compound or biomoleculecompound conjugate according to the present disclosure. In other examples, decreases are expressed as a fold change, such as a decrease in the viability by at least 2-fold, at least 3- fold, at least 4-fold, at least 5-fold, at least 8-fold, at least 10-fold, or even at least 15 or 20- fold, relative to the viability observed with a composition that does not include a compound or biomolecule-compound conjugate according to the present disclosure. Such decreases can be measured using the methods disclosed herein.

[0080] Disulfide: -SSRa, wherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Disulfide groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0081] Dithiocarboxylic: -C(S)SR3wherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Dithiocarboxylic groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0082] Ether: -aliphatic-O-aliphatic, -aliphatic-O-aromatic, -aromatic-O-aliphatic, or - aromatic-O-aromatic, including any polymers thereof having repeats of any such groups (e.g., polyalkene oxide compounds). Ether groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0083] Halo (or halide or halogen): Fluoro, chloro, bromo, or iodo. In some aspects, halo can also include astatine.

[0084] Haloaliphatic: An aliphatic group wherein one or more hydrogen atoms, such as one to 10 hydrogen atoms, independently is replaced with a halogen atom, such as fluoro, bromo, chloro, or iodo. Haloaliphatic groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0085] Haloaliphatic-aryh An aryl group that is or can be coupled to a compound disclosed herein, wherein the aryl group is or becomes coupled through a haloaliphatic group. Haloallphatic-aryl groups can be substituted with one or more groups other than4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0086] Hatoahphatic-heteroaryk A heteroaryl group that is or can be coupled to a compound disclosed herein, wherein the heteroaryl group is or becomes coupled through a haloaliphatic group. Haloaliphatic-heteroaryl groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0087] Hatealkyh An alkyl group wherein one or more hydrogen atoms, such as one to 10 hydrogen atoms, independently is replaced with a halogen atom, such as fluoro, bromo, chloro, or iodo. Haloalkyl groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. In an independent embodiment, haloalkyl can be a CX’3group, wherein each X’ independently can be selected from fluoro, bromo, chloro, or iodo.

[0088] Hatoheteroaiiphatsc: A heteroaliphatic group wherein one or more hydrogen atoms, such as one to 10 hydrogen atoms, independently is replaced with a halogen atom, such as fluoro, bromo, chloro, or iodo. Haloheteroaliphatic groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0089] Heteroaliphatic: An aliphatic group comprising at least one heteroatom to 20 heteroatoms, such as one to 15 heteroatoms, or one to 5 heteroatoms, which can be selected from, but not limited to oxygen, nitrogen, sulfur, silicon, boron, selenium, phosphorous, and oxidized forms thereof within the group. Alkoxy, ether, amino, disulfide, peroxy, and thioether groups are exemplary (but non-limiting) examples of heteroaliphatic. Heteroaliphatic groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0090] Heteroaliphatic-aryl: An aryl group that is or can be coupled to a compound disclosed herein, wherein the aryl group is or becomes coupled through a heteroaliphatic group. Heteroaliphatic-aryl groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0091] Heteroaryl : An aryl group comprising at least one heteroatom to six heteroatoms, such as one to four heteroatoms, which can be selected from, but not limited to oxygen,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 nitrogen, sulfur, silicon, boron, selenium, phosphorous, and oxidized forms thereof within the ring. Such heteroaryl groups can have a single ring or multiple condensed rings, wherein the condensed rings may or may not be aromatic and / or contain a heteroatom, provided that the point of attachment is through an atom of the aromatic heteroaryl group. Heteroaryl groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0092] Heteroatom: An atom other than carbon or hydrogen, such as (but not limited to) oxygen, nitrogen, sulfur, silicon, boron, selenium, or phosphorous. In particular disclosed aspects, such as when valency constraints do not permit, a heteroatom does not include a halogen atom.

[0093] isothiocyanate: -N=C=S.

[0094] IR700 (IRDye® 700DX): A silicon phthalocyanine dye having the following formula:IR700 NHS EsterIR700 is currently commercially available from LI-COR (Lincoln, NE). Amino-reactive IR700 is a relatively hydrophilic dye and can be covalently conjugated with an antibody using the NHS ester of IR700.

[0095] Ketone: -C(O)Ra, wherein Rais selected from aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Ketone groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0096] Maleimide: A chemical group having a core structure, wherein the core structure can comprise substituents bound to the ring carbon atoms.

[0097] Organic Functional Group: A functional group that may be provided by any combination of aliphatic, heteroaliphatic, cycloaliphatic, cycloheteroaliphatic, cyclohaloaliphatic, aromatic, and / or haloaliphatic groups, or that may be selected from, but not limited to, aldehyde (i.e., -C(O)H); aroxy (i.e., -O-aromatic); acyl halide (i.e., -C(O)X,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 wherein X' is a halogen, such as Br, F, I, or Cl); halogen; nitro (I.e., -NO2); cyano (i.e., -CN); azide (i.e., -N3); carboxyl (i.e., -C(O)OH); carboxylate (i.e., -C(O)O or salts thereof, wherein the negative charge of the carboxylate group may be balanced with an M+counterion, wherein M+may be an alkali ion, such asNa+, Li+; an ammonium ion, such as ’N(RbL where Rbis hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group; or an alkaline earth ion, such as [Ca2+]o.s, [Mg2+]o.s, or [Ba2+]o.s); amide (i.e., -C(O)NRaRbor -NRaG(O)Rbwherein each of Raand Rbindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); ketone (i.e., -C(O)Ra, wherein Rais selected from aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); carbonate (i.e., -OC(O)ORa, wherein Rais selected from aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); imine (i.e., -C(=NRa)Rbor -N=CRaRb, wherein Raand Rbindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); azo (i.e., NkNRawherein Rais hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); carbamate (i.e.. -OC(O)NRaRb, wherein each of Raand Rbindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); hydroxyl (i.e., -OH); thiol (i.e., -SH); sulfonyl (i.e., -SO?Ra, wherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); sulfonate (i.e., -SO3 , wherein the negative charge of the sulfonate group may be balanced with an M+counter ion, wherein M+may be an alkali ion, such as K+, Na+, Li+; an ammonium ion, such as+N(Rb)< where Rbis hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group; or an alkaline earth ion, such as [Ca2+]u.5, [Mg2^s.5, or [Ba2’]o.5); oxime (i.e., -CRa-NOH, wherein Rais hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); sulfonamide (i.e., -SOsNR-^R1- or -N(Ra)SO2Rb, wherein each of Raand Rbindependently is selected from hydrogen, aliphatic, heteroaliphatic, haioaliphatic, aromatic, or an organic functional group): ester (i.e., -C(O)ORaor -OC(O)Ra, wherein Rais selected from aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group): thiocyanate (i.e., -S- CN or -N=C=S); thioketone (i.e., -C(S)Rawherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); thiocarboxylic acid (i.e., -C(O)SH, or -C(S)OH); thioester (i.e., -C(O)SRaor -C(S)ORawherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); dithiocarboxylic acid or ester (i.e., -C(S)SRawherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); phosphonate (i.e., -P(O)(ORa)2, wherein each Raindependently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group; or wherein one or more Ragroups are not present and the phosphate group therefore has at least one4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 negative charge, which can be balanced by a counterion, M+, wherein each M+independently can be an alkali ion, such as K4, Na4, Li4; an ammonium ion, such as4N(Rb)4where Rbis hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic- functional group; or an alkaline earth ion, such as [Ca2'*]o.5, [Mg2+]o.s, or [Ba2+]o.s); phosphate (i.e., -O-P(O)(ORa)2, wherein each Raindependently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group; or wherein one or more Ragroups are not present and the phosphate group therefore has at least one negative charge, which can be balanced by a counterion, M+, wherein each M+independently can be an alkali ion, such as K+, Na‘, Li+; an ammonium ion, such as 'N(where Rbis hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group; or an alkaline earth ion, such as [Ca2*]o.5, [Mg2*]o.s, or [Ba2*]o.s); silyl ether (i.e., -OSiRaRbRc, wherein each of Ra, Rb, and Rcindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); sulfinyl (i.e., -S(O)Ra, wherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, aromatic, or an organic functional group); thial (i.e., -C(S)H); or combinations thereof.

[0098] Oxime: -CRa=NOH, wherein Rais hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Oxime groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0099] Peroxy: -O-ORawherein Rais hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Peroxy groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0100] Pharmaceutical Composition: A chemical compound or composition capable of inducing a desired therapeutic or prophylactic effect when properly administered to a subject. A pharmaceutical composition can include a therapeutic agent, such as one or more compounds or biomolecule-compound conjugates according to the present disclosure. A therapeutic or pharmaceutical agent is one that alone or together with an additional compound induces the desired response (such as inducing a therapeutic or prophylactic effect when administered to a subject). In a particular example, a pharmaceutical composition includes a therapeutically effective amount of at least one compound or biomolecule-compound conjugate disclosed herein.

[0101] Pharmaceutically Acceptable Salt: A biologically compatible salt of a disclosed conjugate (or compound portion thereof), which salts are derived from a variety of organic4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 and Inorganic counter ions well known in the art and include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the molecule contains a basic functionality, salts of organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate, and the like. Pharmaceutically acceptable acid addition salts are those salts that retain the biological effectiveness of the free bases while formed by acid partners that are not biologically or otherwise undesirable, e.g., inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, as well as organic acids such as acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. Pharmaceutically acceptable base addition salts include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Exemplary salts are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2- dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. (See, for example, S. M. Berge, et al., “Pharmaceutical Salts,” J. Pharm. ScL 1977; 66:1 -19, the relevant portion of which is incorporated herein by reference.)

[0102] Pharmaceutically Acceptable Vehicles: The pharmaceutically acceptable carriers (vehicles) useful in this disclosure typically are conventional. Flemington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, PA, 19th Edition (1995), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compounds, such as one or more biomolecule-compound conjugates according to the present disclosure.

[0103] In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (for example, powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate, in addition to biologically-neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.

[0104] Phosphate: -O-P(O)(ORa)2, wherein each Raindependently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group; or wherein one or more Ragroups are not present and the phosphate group therefore has at least one negative charge, which can be balanced by a counterion, M+, wherein each M+independently can be an alkali ion, such as K+, Na*, Li*; an ammonium ion, such as *N(Rb)4where Rbis H, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, or aromatic; or an alkaline earth ion, such as [Ca2‘]o.5, [Mg2*]o.s, or [Ba2*]o.s. The Ragroups of the phosphate can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haioaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0105] Phosphonate: -P(O)(ORa)z, wherein each R3independently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group; or wherein one or more R® groups are not present and the phosphonate group therefore has at least one negative charge, which can be balanced by a counterion, M L wherein each IVT independently can be an alkali ion, such as K*, Na+, Li+; an ammonium ion, such as+N(Rb)4 where Rbis H, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, or aromatic; or an alkaline earth ion, such as [Ca2+]o5, [Mg2+]o.s, or [Ba2i]o.s. The R® groups of the phosphonate group can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0106] Photoimmunotherapy (PIT): A molecular targeted therapy that utilizes a targetspecific photosensitizer comprising a silicon phthalocyanine dye conjugated to a monoclonal antibody (MAb), which can target cell surface receptors. In one example the cell surface receptor is one found specifically on cancer cells, such as HER1 , HER2 or PSMA, and thus PIT can be used to kill such cells. In particular aspects of the disclosure, the PIT methods utilize a biomolecule-compound conjugate that comprises an antibody bound to a compound via a linker group as disclosed herein. Cell death of the ceils occurs when the biomoleculecompound conjugate binds to the cells and the cells are irradiated with NIR, while cells that do not express the cell surface receptor recognized by the biomolecule-compound conjugate are not killed in significant numbers.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0107] Silyl Ether: -OSiRaRbRc, wherein eac-h of Ra, Rb, and Rcindependently is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Silyl ether groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0108] Specifically binds: This phrase refers to the ability of individual antibodies to specifically immunoreact with an antigen, such as a tumor-specific antigen, relative to binding to unrelated proteins, such as non-tumor proteins, for example p-actin. For example, a HER2-specific binding agent binds substantially only the HER-2 protein in vitro or in vivo. As used herein, the term “tumor-specific binding agent” includes tumor-specific antibodies and other agents that bind substantially only to a tumor-specific protein in that preparation.

[0109] The binding is a non-random binding reaction between an antibody molecule and an antigenic determinant of the T cell surface molecule. The desired binding specificity is typically determined from the reference point of the ability of the antibody to differentially bind the T cell surface molecule and an unrelated antigen, and therefore distinguish between two different antigens, particularly where the two antigens have unique epitopes. An antibody that specifically binds to a particular epitope is referred to as a "specific antibody".

[0110] In some examples, an antibody (such as an antibody-compound conjugate disclosed herein) specifically binds to a target (such as a cell surface protein) with a binding constant that is at least 103M1greater, 10“ M!greater or 105M1greater than a binding constant for other molecules in a sample or subject. In some examples, an antibody (e.g., monoclonal antibody) or fragments thereof, has an equilibrium constant (Kd) of 1 nM or less. For example, an antibody binds to a target, such as tumor-specific protein with a binding affinity of at least about 0.1 x i O8M, at least about 0.3 x 10-8M, at least about 0.5 x WsM, at least about 0.75 x 108M, at least about 1.0 x 108M, at least about 1 .3 x 108M at least about 1 .5 x 10sM, or at least about 2.0 x 10'8M. Kd values can, for example, be determined by competitive ELISA (enzyme-linked immunosorbent assay) or using a surface-plasmon resonance device such as the Biacore TWO, which is available from Biacore, Inc., Piscataway, NJ.

[0111] Subject or patient: A term that includes human and non-human mammals. In one example, the subject is a human or veterinary subject, such as a mouse. In some examples, the subject is a mammal (such as a human) who has cancer, or is being treated for cancer;4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 or who has been infected by a pathogenic species (e.g., a virus, fungus, parasite, bacterial cell, or the like). o<^Nv-'-0

[0112] Succinimide (NHS): A chemical group having a core structure of ' — i , wherein the core structure can include substituents attached to the ring carbon atoms. Succinimide groups can be coupled to a carboxylic acid to provide an activated ester.

[0113] Sulfinyl : -S(O)Ra, wherein R8is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Sulfinyl groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0114] Sulfonyl: -SO2R8, wherein R8is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Sulfonyl groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0115] Sulfanamide: -SO2NRfcRcor -N(Rb)SO2R°, wherein each of Rband R1' independently Is selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group. Sulfonamide groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.

[0116] Sulfonate: -SO3 , wherein the negative charge of the sulfonate group may be balanced with an M+counter ion, wherein M* may be an alkali ion, such as K4, Na-, Li4; an ammonium ion, such as+N(Rb)4where Rbis H, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, or aromatic; or an alkaline earth ion, such as [Ca?+]o.5, [Mg;’+]o.s, or [Bai:+]o.5.

[0117] Therapeutically Effective Amount: An amount of a compound, biomoleculecompound conjugate, or composition that alone, or together with an additional therapeutic agent(s) (such as a chemotherapeutic agent), is sufficient to achieve a desired effect in a subject, or in a cell, being treated with the agent. The effective amount of the agent (such as a compound or biomolecule-compound conjugate according to the present disclosure) can be dependent on several factors, including, but not limited to the subject or cells being treated, the particular therapeutic agent, and / or the manner of administration of the therapeutic composition. In one example, a therapeutically effective amount or concentration is one that is sufficient to prevent advancement (such as metastasis), delay4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 progression, or to cause regression of a disease, or which is capable of reducing symptoms caused by the disease, such as cancer or a pathogen (e.g., a virus, fungus, parasite, bacterial cell, or the like). In one example, a therapeutically effective amount or concentration is one that is sufficient to increase the survival time of a patient with a tumor or that can minimize or eliminate symptoms associated with an infectious disease caused by a pathogenic species.

[0118] In one example, a desired response is to reduce or inhibit one or more symptoms associated with cancer. The one or more symptoms do not have to be completely eliminated for the composition to be effective. For example, administration of a composition containing a biomolecule-compound conjugate of the present disclosure, followed by irradiation, can decrease the size of a tumor (such as the volume or weight of a tumor, or metastasis of a tumor), for example by at least 20%, at least 50%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100%, as compared to the tumor size in the absence of the biomolecule-compound conjugate. In one particular example, a desired response is to kill a population of cells by a desired amount, for example by killing at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% of the cells, as compared to the cell killing in the absence of the biomolecule-compound conjugate and irradiation. In one particular example, a desired response is to increase the survival time of a patient with a tumor (or who has had a tumor recently removed) by a desired amount, for example increase survival by at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 9o%, at least 98%, or even at least 100%, as compared to the survival time in the absence of the biomolecule-compound conjugate and irradiation.

[0119] The effective amount of an agent that includes one of the disclosed compounds or biomolecule-compound conjugates, that is administered to a human or veterinary subject, will vary depending upon a number of factors associated with that subject, for example the overall health of the subject. An effective amount of an agent can be determined by varying the dosage of the product and measuring the resulting therapeutic response, such as the regression of a tumor. Effective amounts also can be determined through various in vitro, in vivo or in situ immunoassays. The disclosed agents can be administered in a single dose, or in several doses, as needed to obtain the desired response. However, the effective amount of an agent can be dependent on the source applied, the subject being treated, the severity and type of the condition being treated, and the manner of administration.

[0120] In particular examples, a therapeutically effective dose of a compound or biomolecule-compound conjugate according to aspects of the present disclosure is at least4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20250.5 milligram per 60 kilogram (mg / kg), at least 5 mg / 60 kg, at least 10 mg / 60 kg, at least 20 mg / 60 kg, at least 30 mg / 60 kg, at least 50 mg / 60 kg, for example 0.5 to 50 mg / 60 kg, such as a dose of 1 mg / 60 kg, 2 mg / 60 kg, 5 mg / 60 kg, 20 mg / 60 kg, or 50 mg / 60 kg, for example when administered intravenously. In another example, a therapeutically effective dose of a compound or biomolecule-compound conjugate is at least 10 pg / kg, such as at least 100 pg / kg, at least 200 pg / kg, or at least 500 pg / kg, for example 10 pg / kg to 1000 pg / kg, such as a dose of 100 pg / kg, 250 pg / kg, about 500 pg / kg, 750 pg / kg, or 1000 pg / kg, for example when administered intratumorally or intraperitoneally. In one example, a therapeutically effective dose is at least 1 pg / ml, such as at least 500 pg / ml, such as between 20 pg / ml to 100 pg / ml, such as 10 pg / ml, 20 pg / ml, 30 pg / ml, 40 pg / ml, 50 pg / ml, 60 pg / ml, 70 pg / ml, 80 pg / ml, 90 pg / ml or 100 pg / ml administered in topical solution. However, one skilled in the art will recognize that higher or lower dosages also could be used, for example depending on the particular compound or biomolecule-compound conjugate used. In particular examples, such daily dosages are administered in one or more divided doses (such as 2, 3, or 4 doses) or in a single formulation. The disclosed compounds and / or biomolecule-compound conjugates of the present disclosure can be administered alone, in the presence of a pharmaceutically acceptable carrier, and / or in the presence of other therapeutic agents (such as other anti -neoplastic agents).

[0121] Generally a suitable dose of irradiation following administration of a compound or biomolecule-compound conjugate is at least 1 J cm2at a wavelength of 650 nm to 1100 nm, for example, at least 10 J cm2at a wavelength of 650 nm to 1100 nm, at least 50 J cm-2at a wavelength of 650 nm to 1100 nm, or at least 100 J cm2at a wavelength of 650 nm to 1 100 nm, for example 1 to 500 J cm2at a wavelength of 650 nm to 1100 nm. In some examples the wavelength is 650 nm to 1100 nm, such as 650 nm to 1000 nm, or 650 nm to 950 nm, or 650 nm to 900 nm, or 650 nm to 850 nm, or 650 nm to 800 nm, or 650 nm to 750 nm, or 650 nm to 700 nm. In specific examples, a suitable dose of irradiation following administration of the compound or biomolecule-compound conjugate is at least 1 .0 J cm2at a wavelength of 690 nm for example, at least 10 J cm2at a wavelength of 690 nm, at least 50 J cm2at a wavelength of 690 nm, or at least 100 J cm2at a wavelength of 690 nm, for example 1 to 500 1 .0 J cm2at a wavelength of 690 nm. In particular examples, multiple irradiations are performed (such as at least 2. at least 3, or at least 4 irradiations, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10 separate administrations), following administration of the compound or biomolecule- compound conjugate.

[0122] Thial: -C(S)H.

[0123] Thiocarboxylic acid: -C(O)SH, or -C(S)OH.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0124] Thiocyanate: -S-CN.

[0125] Thioester: -C(O)SRaor -C(S)ORawherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaiiphatic, aromatic, or an organic functional group. Thioester groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaiiphatic, aromatic, or an organic functional group.

[0126] Thioether: -S-aliphatic or -S-aromatic, such as -S-alkyl, -S-alkenyl, -S-alkynyl, -S- aryi, or -S-heteroaryl; or -aliphatic-S-aliphatic, -aliphatic-S-aromatic, -aromatic-S-aiiphatic, or -aromatic-S-aromatic. Thioether groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaiiphatic, aromatic, or an organic functional group.

[0127] Thioketone: -C(S)Rawherein Rais selected from hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaiiphatic, aromatic, or an organic functional group. Thioketone groups can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaiiphatic, aromatic, or an organic functional group.

[0128] Treatmg / Treatment: Treatment of a disease or condition of interest in a subject, particularly a human, canine, or feline, having the disease or condition of interest, and includes by way of example, and without limitation:(i) prophylactic administration to prevent the disease or condition from occurring in a subject, or to ameliorate symptoms associated with the condition if required in particular, when such subject is predisposed to the condition but has not yet been diagnosed as having it;(ii) inhibiting the disease or condition, for example, arresting or slowing its development;(iii) relieving the disease or condition, for example, causing regression of the disease or condition or a symptom thereof; or(iv) stabilizing the disease or condition.As used herein, the terms “disease” and “condition” can be used interchangeably or can be different in that the particular malady or condition may not have a known causative agent (so that etiology has not yet been determined) and it is therefore not yet recognized as a disease but only as an undesirable condition or syndrome, where a more or less specific set of symptoms have been identified by clinicians.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0129] Tumor, neoplasm, malignancy or cancer: A neoplasm is an abnormal growth of tissue or cells which results from excessive cell division. Neoplastic growth can produce a tumor. The amount of a tumor in an individual is the “tumor burden" which can be measured as the number, volume, or weight of the tumor. A tumor that does not metastasize is referred to as “benign.” A tumor that invades the surrounding tissue and / or can metastasize is referred to as “malignant.” A “non-cancerous tissue” is a tissue from the same organ wherein the malignant neoplasm formed, but does not have the characteristic pathology of the neoplasm. Generally, noncancerous tissue appears histologically normal. A “normal tissue” is tissue from an organ, wherein the organ is not affected by cancer or another disease or disorder of that organ. A “cancer-free” subject has not been diagnosed with a cancer of that organ and does not have detectable cancer.

[0130] Exemplary tumors, such as cancers, that can be treated with biomolecule-compound conjugates (including compositions thereof) disclosed herein include solid tumors, such as breast carcinomas (e.g. lobular and duct carcinomas), sarcomas, carcinomas of the lung (e.g., non-smail cell carcinoma, large cell carcinoma, squamous carcinoma, and adenocarcinoma), mesothelioma of the lung, colorectal adenocarcinoma, stomach carcinoma, prostatic adenocarcinoma, ovarian carcinoma (such as serous cystadenocarcinoma and mucinous cystadenocarcinoma), ovarian germ cell tumors, testicular carcinomas and germ ceil tumors, pancreatic adenocarcinoma, biliary adenocarcinoma, hepatocellular carcinoma, bladder carcinoma (including, for instance, transitional cell carcinoma, adenocarcinoma, and squamous carcinoma), renal cell adenocarcinoma, endometrial carcinomas (including, e.g., adenocarcinomas and mixed Mullerian tumors (carcinosarcomas)), carcinomas of the endocervix, ectocervix, and vagina (such as adenocarcinoma and squamous carcinoma of each of same), tumors of the skin (e.g., squamous cell carcinoma, basal cell carcinoma, malignant melanoma, skin appendage tumors, Kaposi sarcoma, cutaneous lymphoma, skin adnexal tumors and various types of sarcomas and Merkel cell carcinoma), esophageal carcinoma, carcinomas of the nasopharynx and oropharynx (including squamous carcinoma and adenocarcinomas of same), salivary gland carcinomas, brain and central nervous system tumors (including, for example, tumors of glial, neuronal, and meningeal origin), tumors of peripheral nerve, soft tissue sarcomas and sarcomas of bone and cartilage, and lymphatic tumors (including B -cell and T- cell malignant lymphoma). In one example, the tumor is an adenocarcinoma.

[0131] The biomolecule-compound conjugates according to the present disclosure can also be used to treat liquid tumors, such as a lymphatic, white blood cell, or other type of leukemia. In a specific example, the tumor treated is a tumor of the blood, such as a4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 leukemia (for example acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CIVIL), hairy cell leukemia (HCL), T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia , and adult T-cell leukemia), lymphomas (such as Hodgkin's lymphoma and nonHodgkin’s lymphoma), and myelomas.

[0132] Under conditions sufficient for: A phrase that is used to describe any environment that permits the desired activity. In one example, “under conditions sufficient for” includes administering a compound or biomolecule-compound conjugate according to the present disclosure to a subject or sample sufficient to allow the compound or biomolecule-compound conjugate to bind to cell surface proteins and / or to target a pathogen. In particular examples, the desired activity is killing the cells and / or pathogenic species to which the compound or biomolecule-compound conjugate is bound, following therapeutic irradiation.

[0133] Untreated cell: A cell that has not been contacted with a desired agent, such as a biomolecule-compound conjugate according to the present disclosure. In an example, an untreated cell is a cell that receives the vehicle in which the desired agent was delivered.

[0134] Introduction

[0135] Conventional photodynamic therapy (PDT), which combines a photosensitizing agent with the physical energy of non-ionizing light to kill cells, has been employed for treating certain disorders / diseases; however, it is less commonly employed for cancer therapy because the current non-targeted photosensitizers are also taken up in normal tissues, thus, causing serious side effects.

[0136] Near-infrared photoimmunotherapy (NIR-PIT) is a molecularly-targeted therapy that induces rapid cancer ceil death by systemically administering an antibody-photoabsorber conjugate (ARC) that binds to cancer cells and irradiating with NIR light, which drives photochemical transformations of the ARC. NIR-PIT can selectively kill cancer cells while leaving normal tissues unaffected. Moreover, NIR-PIT activates anti-cancer immunity through the induction of immunogenic cell death of cancer cells. APCs used for NIR-PIT typically comprise a monoclonal antibody that can target a cancer cell surface antigen, wherein the antibody is conjugated to a photoactivatable dye compound. An example of a photoactivatable dye used in the art is IR700 (also referred to as IRDye® 700DX).Improving PIT, however, will require developing new photosensitizers that exhibit improved and / or tunable activity. This is an obstacle not yet addressed in the art, however, due to the4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 difficulty of synthesizing A3B-type asymmetric silicon phthalocyanine dyes. For example, IR700 compounds that have been developed in the art have specific linker groups that extended from the phthalocyanine core solely by an ether linkage (i.e., through tin oxygen atom). This linkage limits the type of chemistry that can be used to attach linker groups as well as the position at which they can be attached.

[0137] The present disclosure is directed to new silicon phthalocyanine-containing compounds (including salts thereof) that comprise unique linker groups and / or substitution patterns that facilitate efficient synthesis methods with improved yields, as well as the ability to modify / tune the particular wavelength used to photoactivate the compounds for therapy. According to aspects of the disclosure, the compounds can be conjugated to various biomolecules for therapeutic and / or diagnostic applications. In particular aspects of the disclosure, the compounds can be conjugated to an antibody for site-directed immunotherapy. In other aspects, the compounds can be used to target and destroy pathogens (e.g., a virus, fungus, parasite, bacterial cell, or the like). Linker groups and substitution patterns used for the compounds and biomolecule-compound conjugates according to the present disclosure are described herein. Also disclosed herein are dimerized compounds comprising two silicon-based phthalocyanine cores wherein the cores are joined together by a fused ring system functionalized with a linker group according to aspects of the present disclosure.

[0138] Compounds and Conjugates

[0139] Disclosed herein are compounds having a structure according to Formula I, ■ ncludmg any pharmaceutically acceptable salts thereof. Also disclosed are compounds having a dimer structure as shown in Formula II. Compounds according to aspects of the present disclosure comprise a unique linker group. In some aspects of the present disclosure, compounds according to Formula I comprise the linker group positioned at the “beta” position on a phenyl ring of the phthalocyanine group (carbon labeled “P” in Formula I). In some other aspects, the linker group may be positioned at the “alpha” position on a phenyl ring of the phthalocyanine group (carbon labeled “a" in Formula I). The unique linker group can be formed by coupling clickable functional groups together (wherein one clickable functional group is coupled to the phthalocyanine core and the other is part of a separate moiety) or by coupling wavelength-tunable groups (e.g., styrene-type groups) to the phthalocyanine core. The ability to provide such linker groups provides flexibility in, for example: (i) the installed linker length, which can be tuned to improve efficacy of cellular cytotoxicity, and (ii) linker identity such that the energy of therapeutic light exposure used during any NIR-PIT can be reduced, thereby improving clinical therapeutic efficacy and4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 safety. Compounds according to Formulas I and II further comprise an X group that facilitates the ability to bind a biomoiecule, including proteins that can target and / or remove pathogens (e.g., a virus, fungus, parasite, bacterial cell, or the like).Formula II

[0140] With reference to Formulas I and II, the following substituent recitations can apply:X is a biomolecule-binding moiety; the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p[O(CR2)t]q-{X}, wherein{Core} solely represents attachment to the phthalocyanine core and {X} solely represents attachment to X: each R, independently for each occurrence, is selected from hydrogen, halogen, aliphatic, heteroaliphatic, or aromatic;Y is selected from (i) a functional group produced from a reaction between two clickable functional groups; (ii) -CH=CH-[Q1]S-, wherein s is 1 or 0 and Q1is4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 selected from aromatic, or -C(=O)Y’- or -S(=O)2Y’, wherein Y' is NR” or O (wherein R" is H, -ON, CF3, or a sulfonyl group, such as SO2Me, SO2GF3, SO2NH2, or SO2NMe2); or (iii) -C^C-Q2, wherein Q2is ~(CH2)uC(=O)Y’-!wherein u is an integer selected from 1 to 10, such as 1 to 8, or 1 to 6 (e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10), Y’ is NR” or O (wherein R” is H, -CN, CF3, or a sulfonyl group, such as SO2Me, SO2CF3, SO2NH2. or SO2NMe2);Z is a heteroatom; m is 1 or 0; each of n, p, and t independently is selected from an integer ranging from 0 to 50; and q is an integer selected from 0 to 50;G, if present, is selected from halogen (such as chloro, bromo, fluoro, or iodo) or a Linker-X group (wherein the linker group and the X group as selected from definitions provided above): each of R1a, R2a, R3a, R1b, R2b, and R3bindependently is selected from hydrogen, aliphatic, halogen, heteroaliphatic, aromatic, thiol, hydroxyl, or amine; or(i) R1aand Rlbjoin together, with the carbon atoms to which they are attached, to form a 6-membered aromatic ring,(ii) R2aand R2bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring,(iii) R3aand R3bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring, or(iv) any combination of two or more of (i)-(iii); andL is selected from -(CH2)r-, -Si(R5)2(CH2)r-, -C(=O)(CH2)r>or -Ph(CH2)r-, wherein each R5independently is aliphatic (such as alkyl, including Cnoalkyl) or aryl (such as phenyl), r is an integer selected from 1 to 5, such as 1 , 2, 3, 4, or 5, wherein any CH2group of the L group is attached to the quaternary amine of Formula I or Formula II.

[0141] In some aspects, X is a biomolecule-binding moiety or a precursor thereto. The biomolecule-binding moiety can be a moiety capable of binding a biomolecule that can be used to facilitate specific binding of the compound to a target. In some aspects of the disclosure, the biomolecule-binding moiety is a moiety that can form a chemical bond with a biomolecule, such as an antibody or other biomolecule capable of specifically binding a target, such target including a cell or a component thereof (e.g., a cell surface protein) or a pathogen (e.g., a virus, fungus, parasite, bacterial cell, or the like). In some aspects, the biomolecule-binding moiety comprises an ester group (e.g., an activated ester group or a precursor thereto), a thiol group, a thiol-reactive group (e.g., maleimide), an amine, or a4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 clickable functional group. In particular aspects of the disclosure, the biomolecule-binding moiety comprises an activated ester group and the biomolecule to which the biomoleculebinding moiety becomes bound is an antibody. In yet other aspects, the biomolecule-binding moiety comprises a clickable functional group that can react with another clickable functional group that is present on the biomolecule. In some such aspects, the biomolecule is a labeled pathogen-specific protein (e.g., a bacteria-specific protein). Exemplary clickable functional groups can be selected from such groups as described for the linker group of the formulas disclosed herein. In yet additional aspects, the biomolecule-binding moiety can be a thiol-reactive group, such as a maleimide, that is capable of binding with a thiol group present on a biomolecule.

[0142] The linker group of Formulas I and II has a structure according to a formula {Core}- (CR2)n-Y-(Z)m-(CR2)p[O(CR2)t]q-{X}, wherein the variables of this formula are defined as above and wherein “{Core}” and “{X}" are provided solely to illustrate how the linker is bound to the phthalocyanme core and variable X of Formula I. In some aspects, the linker group has a structure according to a formula {Core}-(CR2)fl-Y-(CR2)p-{X}, {Core}-(CR2)n-Y- (CR2)P[O(CR2)i]q-[X}, {Core}-(CR2)n-Y-(Z)m-(CR2)P-{X}>or {Core}-(CR2)r,-Y- (Z)m(CR2)p[O(CR2)i]q-{X}. In some aspects of the disclosure, at least one of n and p is selected from an integer greater than zero such that R groups are present. In such aspects, each R group independently, for each occurrence, is selected from hydrogen, Cl, F, Br, I, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloheteroalkyl, cycloheteroalkenyl, cycloheteroalkynyl, aryl, or heteroaryl.In some particular aspects, each R group independently, for each occurrence, is hydrogen or lower alkyl (e.g., methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, or decyl). In particular aspects, each of n, p, and / or t independently is an integer selected from 0 to 50, such as 0 to 25, or 0 to 24, or 0 to 23, or 0 to 22, or 0 io 21 , or 0 to 20, or 0 to 15, or 0 to 10, or 0 to 9. In some aspects, each of n, p, and / or t independently is selected from 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10. In particular aspects, n is an integer selected from 0, 1 , 2, 3, or 4, more particularly 0, 1 , 2, or 3. In particular aspects, p or t independently is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, or 25.In some aspects of the present disclosure, q is an integer selected from 0 to 50 such as 0 to 25, or 0 to 20, or 0 to 15, or 0 to 10, or 0 to 9, or 0 to 8, or 0 to 7, or 0 to 6, or 0 to 5, or 0 to 4, or 0 to 3, or 0 to 2. In particular aspects, q is either 0 or is 1 to 6 (e.g., 1 , 2, 3, 4, 5, or 6).

[0143] In some aspects of the disclosure, Y is a moiety that is provided by reacting two clickable functional groups. In such aspects, m typically is zero and thus no Z group is present. In some aspects, Y comprises a ring formed by a cycloaddition reaction between4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025(i) an alkyne and an azide; (ii) a tetrazine and a trans-cyclooctene; (iii) an azide and a dibenzocyclooctyne (DBCO); or (iv) an azide and a bicyclo[6.1 .OJnonyne. In some aspects, Y comprises a triazole, a cyciooctafc^pyridazine, a cycloocta[d|triazole, a triazole- functionalized DBCO, or the like. In particular aspects of the present disclosure, the phthalocyanine core can be functionalized with an alkyne, dibenzocyclooctyne, or bicyclo[6.1 .0]nonyne, and a separate moiety comprising the biomolecule-binding moiety can be functionalized with an azide. In yet other aspects, the phthalocyanine core can be functionalized with an azide, and a separate moiety comprising the biomolecule-binding moiety can be functionalized with a terminal or di-substituted alkyne, dibenzocyclooctyne, or a bicyclo[6.1.0]nonyne group. In yet additional aspects, the phthalocyanine core can be functionalized with a tetrazine, and a separate moiety comprising the biomolecule-binding moiety can be functionalized with a trans-cyclooctene group, in yet other aspects, the phthalocyanine core can be functionalized with a trans-cyclooctene group, and a separate moiety comprising the biomolecule-binding moiety can be functionalized with a tetrazine. In exemplary aspects, ihe phthalocyanine core is functionalized with an alkyne or an azide and the separate moiety comprising the biomolecule-binding moiety is functionalized with an azide (if the phthalocyanine core is functionalized with an alkyne) or an alkyne (if the phthalocyanine core is functionalized with an azide).

[0144] Those in the art recognize, particularly with the benefit of the present disclosure, reaction conditions that can be used to facilitate bond formation between the clickable functional groups described above, in some aspects of the disclosure, the reaction conditions can include using copper mediated catalysis or ruthenium-mediated catalysis. In yet other aspects of the disclosure, the reaction conditions can comprise incubating the functionalized phthalocyanine core with the separate moiety comprising the biomoleculebinding moiety at physiological pH. In some such aspects of the disclosure, the reaction can be carried out under a pH ranging from 6.5 to 8, such as 7 to 8, or 7 to 7.5 and a buffer can be used.

[0145] In other aspects of the disclosure, Y is a group having a structure of -CH=CH-[Q1]S- wherein s is 1 or 0. When s is 1 , Q1is aromatic, -C(=O)Y’-, or -S(=O)2Y’, and (I) the aromatic group is selected from an aryl (e.g., phenyl, naphthyl, anthracenyl, or the like) or a heteroaryl group (e.g., a pyridinyl, furanyl, pyrroyl, thiophenyl, indolyl, benzofuranyl, carbazoyl, quinolinyl, isoquinolinyl, imidazoyl, oxazoyl, pyrazoyl, pyriazinyl, pyrimidinyl, and the like); or(ii) Y’ of -C(=O)Y’- and / or -S(=O)2Y’ is O or -NH, -N(CN), -NCF3, -NSO2Me, -NSOZCF3, - NSO2NH2, or -NSO2NMe2. In particular aspects wherein Y is -CH-CH-Aromatic-, the aromatic group is a phenyl group or a pyridyl group. In aspects wherein Y is -CH=CH-4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Aromatic-, m can be zero or 1 and typically is 1 . In aspects wherein m is 1 , Z is present and is a heteroatom selected from oxygen, sulfur, or nitrogen. In particular aspects, Z is oxygen.

[0146] In yet other aspects of the disclosure, Y is a group having a structure according to - C^C-Q2, wherein Q2is -(CH2)UC(=O)Y’-, wherein u is an integer selected from 1 to 10, such as 1 to 8, some such aspects,

[0147] In aspects of the disclosure, G is not present. In other aspects, G is present and is selected from chloro, bromo, fluoro, iodo, or Linker-X, wherein the linker and X groups of Linker-X are as defined herein for Formula I and other formulas of the disclosure. In some particular aspects, G is positioned ortho to the Linker-X group illustrated in Formula I. In some aspects of the disclosure, G is Linker-X and this Linker-X group comprises a linker and an X group that are both the same as the linker and X groups of the Linker-X group illustrated in Formula I. In yet some other aspects of the disclosure, G is Linker-X and this Linker-X group comprises a linker that is the same as the linker of the Linker-X group illustrated in Formula I and an X group that is different from X of the Linker-X group illustrated in Formula I. In yet other aspects of the disclosure, G is Linker-X and this Linker- X group comprises a linker that is different from the linker of the Linker-X group illustrated in Formula I and an X group that is the same as X of the Linker- X group illustrated in Formula I. In yet additional aspects, G is Linker-X and this Linker-X group comprises a linker and an X group that are both different from the linker and X groups of the Linker-X group illustrated in Formula I.

[0148] In aspects of the disclosure, each of R1a, R2a, R3a, R1b, R2b, and R3b, independently and for each occurrence is selected from hydrogen, hydroxyl, ether, thiol, thioether, NHs, or amine; or (i) Riaand R.1bjoin together, with the carbon atoms to which they are attached, to form a phenyl ring, (ii) R3aand R2bjoin together, with the carbon atoms to which they are attached, to form a phenyl ring, and (lii) R3aand R3bjoin together, with the carbon atoms to which they are attached, to form a phenyl ring. In such aspects, the phenyl ring can be unsubstituted or unsubstituted with substituents described in definitions provided herein.

[0149] In some aspects, L is selected from -(CH2)4, -SifMeMCHsls-, -Si(Et)2(CH2)3-, - Si( / Pr)2(CH2)s-, -Si(Ph)2(CH2)3-, -C(=O)(CH2)3-, or -PhCHa-, wherein any CHa group of the L group is attached to the quaternary amine of Formula I or Formula II.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0150] in some aspects, compounds of Formula I can have a structure according one of Formulas IA or IB, shown below. In any aspects, the Si(R5)2(CH2)3 groups illustrated in the formulas can be replaced with a-C(=O)(CH2)3-, or -PhCH2- group.Formula IB

[0151] In some aspects, compounds according to Formula I and Formula IA can have structures according to Formula I A(i), Formula IA(ii), Formula I A(iii), or Formula IA(iv), wherein ring A is either an aryl ring, a heteroaryl ring, or a ring system provided by coupling clickable functional groups as described herein. Each of R1a, R?a, R3®, R10, Ra, R3b, R5, X, G, Z, Q1, Q2, m, n, p, q, and s is as described above for any of the preceding formulas. In particular aspects of Formula I A(i) or Formula I A(ii), ring A is a ring system selected from a phenyl ring, a triazole, a cycloocta[d|pyridazine, a cycloocta[d|triazole, or a triazole- functionalized DBCO. In some particular aspects, the alkene group attached to ring A is present or is absent, as represented by the option of 1 or 0 in the formulas. When present, the alkene group is bound to ring A which typically is phenyl or pyridyl. In some such aspects, Z is present and is a heteroatom (e.g., O). When the alkene group is absent, ring A typically is a triazole, a cyclooctafdjpyridazine, a cycloocta[d]triazole, or a triazole- functionalized DBCO. In any aspects, the Si(R5)2(CH2)3 groups illustrated in the formulas can be replaced with a -(CHsh-, -C(=O)(CH2)3-, or -PI1CH2- group. In some aspects, each R5independently is methyl, ethyl, / propyl, or phenyl. The dashed bonds in the formulas below are intended to indicate that a G group can be present (and bound to the carbon to which4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the dashed bond is attached) or that a G group is not present (and the carbon to which the dashed bond is attached is instead attached to a hydrogen atom). In particular aspects, Q1is -C(=O)NH- or -S(=O)2NH- wherein the C or S atoms are bound to the alkene group of Formula IA(iii). In particular aspects, G is chloro, iodo, bromo, or comprises the same linker and X combination as shown in any of Formula IA(i), Formula IA(ii), Formula lA(ili). or Formula IA(iv).Formula IA(iii)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IA(iv)

[0152] In some aspects, compounds according to Formula IA and / or Formula IA(I) can have structures according to Formulas IA(i)(a)-IA(i)(i). With reference to Formulas I A(i)(a)~ I A(i)(i), each of R1a, R2a, R3a, R1b, R2b, R3b, R5, X, G, Z, Y’, n, p, and q is as described above for any of the preceding formulas and Z is N or CH. In particular aspects of Formula IA(i)(a), Formula IA(i)(c), Formula IA(i)(e), Formula IA(i)(f), Formula IA(i)(g), Formula IA(i)(h), Formula IA(i)(i), X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula -C(O)O M\ wherein M is a monovalent counterion), an azide, or an alkyne; G is chloro, iodo, bromo, or comprises the same linker and X combination as shown in any of Formulas IA(i)(a)-IA(i)(i); each R5independently is methyl, ethyl, / propyl, or phenyl; n is an integer selected from 0 to 3 (such as 0, 1 , 2, or 3); p is an integer selected from 0 to 21 (such as 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17. 18. 19, 20, or 21 ); and q is an integer selected from 0 to 6 (such as 0, 1 , 2, 3, 4, 5, or 6). In particular aspects of Formula I A(i)(b) or Formula IA(i)(d), Z is oxygen, Z’ is CH or N, X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula - C(O)O M+, wherein M is a monovalent counterion), an azide, or an alkyne; p is an integer selected from 0 to 21 (such as 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 ); and q is an integer selected from 0 to 6 (such as 0, 1 , 2, 3, 4, 5, or 6). In any aspects, the Si(R5)2(CH2)3 groups illustrated in the formulas can be replaced with a -(CH2)4-, -C(=O)(CH2)3-, or -PhCHg- group. The dashed bonds in the formulas below are intended to indicate that a G group can be present (and bound to the carbon to which the dashed bond is attached) or that a G group is not present (and the carbon to which the dashed bond is attached is instead attached to a hydrogen atom).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula I A(l)(c)Formula IA(l)(d)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula I A(l)(g)Formula IA(l)(h)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IA( i)(i)

[0153] In some aspects, compounds according to Formula I and Formula IB can have structures according to Formula IB(i) or Formula IB(ii), wherein ring A is either an aryl ring, heteroaryl ring, or a ring system provided by coupling clickable functional groups as described herein. Each of R1a, R8a, R3a, R1b, Ra, R3b, R5, X, G, Z, m, n, p, and q is as described above for any of the preceding formulas. In some particular aspects, the alkene group attached to ring A is present or is absent. When present, the alkene group is typically bound to ring A which is phenyl or pyridyl. In some such aspects, Z is present and is a heteroatom (e.g., O). When the aikene group is absent, ring A typically is a triazole, a cycloocta[d|pyridazine, a cycloocta[djtriazole, or a triazole-functionalized DBCO. in any aspects, the Si(R5)2(CH2)3 groups illustrated in the formulas can be replaced with a -(CFte)*-. -C(=O)(CH2)3-, or -PhCH?- group. Additional compounds can have Formulas according to Formulas I A(i)- 1 A(iv) wherein the core comprises the fused naphthalene ring system shown in Formulas IB(i) and IB(ii). The dashed bonds in Formula IB(i) and IB(ii) are intended to indicate that a G group can be present (and bound to the carbon to which the dashed bond is attached) or that a G group is not present (and the carbon to which the dashed bond is attached is instead attached to a hydrogen atom). In particular aspects, G is chloro, iodo, bromo, or comprises the same linker and X combination as shown in Formula I B(i) or Formula IB(ii). In some aspects, each R5independently is methyl, ethyl, / propyl, or phenyl.Formula IB(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IB(ii)

[0154] In some aspects, compounds according to Formula IB(i) can have structures according to Formulas IB(i)(a)-IB(i)(d). With reference to Formulas IB(i)(a)-IB(i)(d), each of R1a, R2a, R3a, R1b, R2b, R3b, Rs, X, G, Z, n, p, and q is as described above for any of the preceding formulas and Z’ is CH or N. In particular aspects of Formula IB(i)(a) and Formula IB(i)(c), X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula -C(O)O M+, wherein M is a monovalent counterion), an azide, or an alkyne; n is an integer selected from 0 to 3 (such as 0, 1 , 2, or 3); G is bromo, chloro, iodo, or comprises the same linker and X combination as shown in Formulas IB(i)(a)-IB(i)(d) ; each R5independently is methyl, ethyl, propyl, or phenyl; p is an integer selected from 0 to 21 (such as 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21); and q is an integer selected from 1 to 6 (such as 1 , 2, 3, 4, 5, or 6). In particular aspects of Formula IB(i)(b) and Formula IB(i)(d), Z is oxygen, Z’ is CH or N, X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula -C(O)O M+, wherein M is a monovalent counterion), an azide, or an alkyne; p is an integer selected from O to 21 (such as O, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21); and q is an integer selected from 1 to 6 (such as 1 , 2, 3, 4, 5, or 6). In any such aspects, the Si(R5)2(CH2)3groups illustrated in the formulas can be replaced 'with a -(CH2)4-, - C(=O)(CH2)3-, or -PhCH2- group. Additional compounds can have Formulas according to Formulas I A(i)(a)-I A(i)(i) wherein the core comprises the fused naphthalene ring system shown in Formulas IB(i)(a)-IB(i)(d). The dashed bonds in the formulas below are intended to indicate that a G group can be present (and bound to the carbon to which the dashed bond is attached) or that a G group is not present (and the carbon to which the dashed bond is attached is instead attached to a hydrogen atom). In particular aspects, G is chloro, iodo, bromo, or comprises the same linker and X combination as shown in any of Formulas IB(i)(a)-IB(i)(d).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula !B(i)(c)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IB(i)(d)

[0155] In some other aspects of the disclosure, the compounds can be dimers having a structure according to Formula II. In some aspects, compounds according to Formula II can have structures according to Formula II A, Formula I IB, or Formula IIC. Each of R1a, R3a, Rlb, R3b, R5, X, Z, Q1, m, n, p, q, and s is as described above for any of the preceding formulas. In particular aspects of Formula HA or Formula I IB, ring A is a ring system selected from a phenyl ring, a pyridyl ring, a triazole, a cyclooctafdjpyridazme, a cycloocta[d|triazole, or a triazole-functionalized DBCO. In some particular aspects, the alkene group attached to ring A is present or is absent. When present, the alkene group is bound to ring A which typically is phenyl or pyridyl. In some such aspects, Z is present and is a heteroatom (e.g., O).When the alkene group is absent, ring A typically is a triazole, a cycloocta[o]pyridazine, a cycloocta[d|triazole, or a triazole-functionalized DBCO. In any aspects, the Si(R5)a(CH2)3 groups illustrated in the formulas can be replaced with a -(CH2)4-, -C(=O)(CH2)3-, or - PhCH2- group. In some aspects of Formula IIC, s is 1 and Q1is -C(=O)Y’ or -S(=O)2Y’, wherein Y’ is O or NH. -N(CN). -NCF3, -NSOsMe, -NSO2CF3, -NSO2NH2, or -NSCbNMe?. In some other aspects of Formula IIC, s is 0. In some aspects, the linker group of Formula HA, IIB, and IIC can comprise a formula according to any of Formulas I A(i)-i A(iv) or Formulas I A(i)(a)-IA(i)(i).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IIB- 4t> -4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IIC

[0156] In some aspects, compounds according to Formula HA can have structures according to Formulas IIA(i) or IIA(il), Formula IIB can have structures according to Formulas IIB(i) and IIB(ii), and Formula IIC can have structures according to Formulas IIC(i), llC(ii), IIG(iii), and IIC(iv), In some aspects, the linker group of Formulas IIA(i), IIA(ii), IIB(i) or I IB(ii) can comprise a formula according to any of Formulas IA(i)-IA(iv) or Formulas IA(i)(a)-IA(i)(i). With reference to Formulas IIA(i), IIA(i), IIB(i), IIB(ii), IIC(i), HC(ii), HC(iii), and liC(iv), each of R1a, R3a, R1b, R3b, R5, X, Z, Z’, Y’, n, p, and q is as described above for any of the preceding formulas. In particular aspects of Formula II A(i) or Formula IIB(i), X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula -C(O;O MT wherein M is a monovalent counterion), an azide, or an alkyne: n is an integer selected from 0 to 3 (such as 0, 1 , 2, or 3); p is an integer selected from 0 to 21 (such as 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 ); and q is an integer selected from 1 to 6 (such as 1 , 2, 3, 4, 5, or 6). In particular aspects of Formula IIA(ii) or IIB(ii) , Z is oxygen, Z’ is CH or N, X is an activated ester (or a precursor thereto, such as a carboxylic acid or a carboxylate having a formula -C(O)O M+, wherein M is a monovalent counterion), an azide, or an alkyne; p is an integer selected from 0 to 21 (such as 0, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 ); and q is an integer selected from 1 to 6 (such as 1 , 2, 3, 4, 5, or 6). In particular aspects of Formula IIC(i) and llC(iii), Y’ is O or -NR, -N(CN), - NCF3, -NSO2Me, -NSO2CF3, -NSO2NH2, or -NSO2NMe2. In any aspects, the Si(R5)2(CH2)3groups illustrated in the formulas can be replaced with a -(CH2)4-, -C(=O)(CH2)3-, or -PhCH2~ group.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IIB(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula SSC(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IIC(iv)4239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0157] Exemplary compounds according to aspects of the disclosure are illustrated below. With reference to any of the below-illustrated species, it is to be understood that the present disclosure also contemplates the same compounds but with the linker groups attached at the alpha carbon instead of the beta carbon as illustrated below, unless otherwise stated.Additionally, the present disclosure also contemplates the same compounds, but wherein any sodium salt form of the illustrated terminal ester group is present as another salt form (e.g., including any M+species, wherein M is a metal) or as the protonated carboxylic acid form. In any of the exemplary compounds shown below, the Si(R5)2(CH2)3 groups (where R5is Me, Et, / Pr, or Ph) illustrated in the formulas can be replaced with a -(Cl-h)?,-, - C(=O)(CH2)3-, or -PhCHj- group.4239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 HLED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0158] Biomolecule-compound conjugates according to the present disclosure can comprise compounds according to any of the formulas described herein wherein the X group is a biomolecule-binding moiety that has been bound to the corresponding biomolecule to which it is designed to bind. In such aspects of the disclosure, the X group and the biomolecule are bound via a chemical bond, typically a covalent bond. In particular aspects, the X group and the biomolecule are bound such that a covalent bond is formed between atoms of the X group and atoms of a functional group of the biomolecule. In certain aspects4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 of the disclosure, the X group is an activated ester, the biomolecuie comprises an amine group, and the covalent bond is formed between the carbonyl of the activated ester and the nitrogen atom of the amine group, thereby forming an amide bond. In exemplary aspects of the disclosure the biomolecule is an antibody, which becomes bound to the compound via a covalent bond between a primary amine of the antibody and a carbonyl group of an activated ester group of the compound. Those in the art, with the benefit of the present disclosure will recognize how biomolecule-compound conjugates are formed for compounds having other X groups and / or biomolecules having other functional groups. These additional types of chemical conjugations also are contemplated by the present disclosure. The disclosed also contemplates pharmaceutically acceptable salts of conjugates described herein.

[0159] Biomolecules suitable for use in coupling with compounds according to the present disclosure to form biomolecule-compound conjugates can typically be selected from antibodies and antibody fragments; however, other biomolecules can include, but are not limited to, Affibody® molecules, haptens, lectins, proteins, nucleic acid molecules, functional nucleic acids, and the like.

[0160] Antibodies and Antibody Fragments

[0161] Antibodies and antibody fragments specific for various molecules are well known in the art. Thus, in some examples, the biomolecule in a biomolecule-compound conjugate according to the present disclosure is an antibody or fragment thereof, permitting specific binding between the antibody or antibody fragment and a target (such as a target protein). Antibodies that can be used in the methods provided herein include intact immunoglobulins, variant immunoglobulins, and portions of antibodies, such as an antigen binding fragment of a naturally occurring or recombinant antibody. In some aspects, the antibody is a humanized antibody (such as a humanized monoclonal antibody) that specifically binds to a surface protein on a cancer cell.

[0162] Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (A) and kappa (k). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE.

[0163] Each heavy and light chain contains a constant region and a variable region, (the regions are also known as “domains"). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a "framework" region interrupted by three hypervariable regions, also called4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025“complementarity-determining regions” or “CDRs.” The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991 , which is hereby incorporated by reference). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species, such as humans. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space.

[0164] The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1 , CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a VL CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. Antibodies with different specificities (i.e. different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved in antigen binding. These positions within the CDRs are called specificity determining residues (SDRs).

[0165] References to “VH” or “VH” refer to the variable region of an immunoglobulin heavy chain, including that of an Fv, scFv, dsFv or Fab. References to “VL" or “VL" refer to the variable region of an immunoglobulin light chain, including that of an Fv, scFv, dsFv or Fab.

[0166] Specific, non-limiting examples of binding fragments encompassed within the term antibody include Fab fragments, Fab' fragments, F(ab)'2 fragments, single chain Fv proteins (“scFv”), and disulfide stabilized Fv proteins (“dsFv"). A scFv protein is a fusion protein in which a light chain variable region of an immunoglobulin and a heavy chain variable region of an immunoglobulin are bound by a linker, while in dsFvs, the chains have been mutated to introduce a disulfide bond to stabilize the association of the chains.

[0167] In one example the Ab is a genetically engineered Ab, such as chimeric antibodies (for example, humanized murine antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, IL); Kuby, J., Immunology, 3rd Ed., W. H. Freeman & Co., New York, 1997. A chimeric antibody has framework residues from one species, such as human, and CDRs (which generally confer antigen binding) from another species, such as a murine antibody that specifically binds human EGFR.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0168] In one example the Ab is a humanized Ab or humanized immunoglobulin. A humanized immunoglobulin is an immunoglobulin including a human framework region and one or more CDRs from a non-human (for example a mouse, rat, or synthetic) immunoglobulin. The non-human immunoglobulin providing the CDRs is termed a “donor,” and the human immunoglobulin providing the framework is termed an “acceptor." In one embodiment, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they must be substantially identical to human immunoglobulin constant regions, i.e., at least about 85- 90%, such as about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDRs, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A humanized antibody is an antibody comprising a humanized light chain and a humanized heavy chain immunoglobulin. A humanized antibody binds to the same antigen as the donor antibody that provides the CDRs. The acceptor framework of a humanized immunoglobulin or antibody may have a limited number of substitutions by amino acids taken from the donor framework. Humanized or other monoclonal antibodies can have additional conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. Humanized immunoglobulins can be constructed by means of genetic engineering (see for example, U.S. Patent No. 5,585,089).

[0169] In one example the Ab is a human antibody (also called a fully human antibody), which includes human framework regions and all of the CDRs from a human immunoglobulin. In one example, the framework and the CDRs are from the same originating human heavy and / or light chain amino acid sequence. However, frameworks from one human antibody can be engineered to include CDRs from a different human antibody. All parts of a human immunoglobulin are substantially identical to corresponding parts of natural human immunoglobulin sequences.

[0170] In one example the Ab is a monoclonal antibody (mAb). A mAb is an antibody produced by a single clone of B lymphocytes or by a cell into which the light and heavy chain genes of a single antibody have been transfected. mAbs are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma ceils with immune spleen cells. mAbs include humanized mAbs.

[0171] As used herein, the term antibody also includes recombinant antibodies produced by expression of a nucleic acid that encodes one or more antibody chains in a cell (for example see U.S. Patent No. 4,745,055; U.S. Patent No. 4,444,487; WO 88 / 03565; EP 256,654; EP4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025120,694; EP 125,023: Faoulkner et al, Nature 298:286, 1982; Morrison, J. Immunol.123:793, 1979; Morrison et al., Ann Rev. Immunol. 2:239, 1984).

[0172] In a specific example, the antibody is a biologic used to treat cancer, such as one specific for a tumor protein. For example, the following antibodies can be used: Panitumumab, Trastuzumab, Zenapax, Simitect, J591 , or Cetuximab.

[0173] Compounds according to the present disclosure can be coupled with antibodies via covalent bonds formed between a functional group of the antibody and the biomoleculebinding moiety of the compound. In particular aspects, an antibody is coupled with the compound by coupling an amine group of the antibody (e.g., an amine of an amino acid of the antibody) with an activated ester of the compound. In some aspects, the amine group of the antibody can be an amine group of a lysine moiety. In some other aspects, the antibody may be bound to the compound via a thioi group that terminates the linker of the compound and a thiol group of the antibody. In yet other aspects, the antibody may be bound to the compound via an amine group that terminates the linker of the compound and an activated ester that is present on the antibody.

[0174] Affibody® molecules

[0175] Affibody® molecules specific for various targets are well known in the art (e.g., from Affibody, Sona, Sweden). Thus, in some examples, the biomolecule in a biomoleculecompound conjugate according to the present disclosure is an Affibody® molecule, permitting specific binding between the Affibody® molecules and a target (such as a target protein). Affibody® molecules are small protein antibody mimetics of about 6 kDa. in some examples, an Affibody® molecule consists of three alpha helices with 58 amino acids. In contrast, a mAb is about 150 kDa, and a single-domain antibody about 12-15 kDa.Affibody® molecules with unique binding properties are typically generated by randomization of 13 amino acids located in two alpha-helices involved in the binding activity of the parent protein domain. In some examples, amino acids outside of the binding surface are substituted in the scaffold to create a surface entirely different from the ancestral protein A domain. Specific Affibody® molecules binding a target protein can be “fished out" from pools (libraries) containing billions of different variants, using phage display.

[0176] Compounds according to the present disclosure can be coupled with an Affibody® via covalent bonds formed between a functional group of the Affibody® and the biomoleculebinding moiety of the compound. In particular aspects, an Affibody® is coupled with the compound by coupling an amine group of the Affibody® (e.g., an amine of an amino acid of4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the Affibody®) with an activated ester of the compound. In some aspects, the amine group of the Affibody® can be an amine group of a lysine moiety. In some other aspects, the Affibody® may be bound to the compound via a thiol group that terminates the linker of the compound and a thiol group of the Affibody®. In yet other aspects, the Affibody® may be bound to the compound via an amine group that terminates the linker of the compound and an activated ester that is present on the Affibody®.

[0177] Haptens

[0178] A hapten is a small molecule that generally can only elicit an immune response when attached to a larger carrier (such as a protein). Haptens are known in the art as incomplete or partial antigens. But because like antibodies they can bind to target molecules, in some examples the biomolecule in a biomolecule-compound conjugate according to the present disclosure is a hapten, permitting specific binding between the hapten and a target (such as a target protein).

[0179] Compounds according to the present disclosure can be coupled with a hapten via covalent bonds formed between a functional group of the hapten and the biomoleculebinding moiety of the compound. In particular aspects, a hapten is coupled with the compound by coupling an amine group of the hapten (e.g., an amine of an amino acid of the hapten) with an activated ester of the compound. In some aspects, the amine group of the hapten can be an amine group of a lysine moiety. In some other aspects, the hapten may be bound to the compound via a thiol group that terminates the linker of the compound and a thiol group of the hapten. In yet other aspects, the hapten may be bound to the compound via an amine group that terminates the linker of the compound and an activated ester that is present on the hapten.

[0180] Lectins

[0181] In one example the biomolecule is a lectin. Lectins are proteins that recognize and bind to specific carbohydrates, for example on the cell surface. Thus, m some examples the biomolecule in a biomolecule-compound conjugate according to the present disclosure is a lectin, permitting specific binding between the lectin and a target carbohydrate. Lectins can be modified to include a protein or peptide extension allowing conjugation / attachment to a compound according to the present disclosure.

[0182] Lectins are found in animals, plants, and microorganisms, and specific examples are known in the art. For example, the plant lectins wheat germ agglutinin, peanut lectin, and phytohemagglutinin recognize different oligosaccharides.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0183] Exemplary lectins that can be used to remove a particular carbohydrate include but are not limited to: concanavalin A, lentil lectin, snowdrop lectin (all which bind mannose); ricin, peanut agglutinin, jacalin, and hairy vetch lectin (all which bind galactose); wheat germ agglutinin (which binds N-acetylglucosamine); elderberry lectin, maackia amurensis hemoagglutinin (all which bind N-acetylneuraminic acid); and ulex europaeus agglutinin and aleuria aurantia lectin (ail which bind fucose).

[0184] Compounds according to the present disclosure can be coupled with a lectin via covalent bonds formed between a functional group of the lectin and the biomolecule-binding moiety of the compound. In particular aspects, a lectin is coupled with the compound by coupling an amine group of the lectin (e.g., an amine of an amino acid of the lectin) with an activated ester of the compound. In some aspects, the amine group of the lectin can be an amine group of a lysine moiety. In some other aspects, the lectin may be bound to the compound via a thiol group that terminates the linker of the compound and a thiol group of the lectin. In yet other aspects, the lectin may be bound to the compound via an amine group that terminates the linker of the compound and an activated ester that is present on the lectin.

[0185] Proteins

[0186] in one example the biomolecule is a protein. Proteins can be used that recognize and bind to specific proteins, nucleic acid molecules, and other binding partners. For example, a protein ligand can be used to bind to a specific receptor protein on a cell surface. Thus, in some examples the biomolecule in a biomolecule-compound conjugate according to the present disclosure is a protein, permitting specific binding between the protein and a target protein, nucleic acid molecule, or other binding molecule, and removal of the molecule which binds to the protein (such as one that forms a covalent bond with the protein).

[0187] Protein-protein interactions are well known in the art, and include those involved in signa! transduction, cellular transport, muscle function (actin / myosin). In addition, protein- nucleic acid molecule interactions are well known in the art, and include those that control the structure and function of the nucleic acid molecule (DNA or RNA), such as transcription, translation, DNA replication, repair and recombination and RNA processing and translocation.

[0188] Compounds according to the present disclosure can be coupled with a protein via covalent bonds formed between a functional group of the protein and the biomoleculebinding moiety of the compound. In particular aspects, a protein is coupled with the4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 compound by coupling an amine group of the protein (e.g., an amine of an amino acid of the protein) with an activated ester of the compound. In some aspects, the amine group of the protein can be an amine group of a lysine moiety. In some other aspects, the protein may be bound to the compound via a thiol group that terminates the linker of the compound and a thiol group of the protein. In yet other aspects, the protein may be bound to the compound via an amine group that terminates the linker of the compound and an activated ester that is present on the protein.

[0189] Nucleic Acid Molecules

[0190] In one example the biomolecule is a nucleic acid molecule. Nucleic acid molecules can be used that recognize and bind to specific proteins, nucleic acid molecules (via hybridization), and other binding partners. For example, a nucleic acid molecule that has sufficient complementarity to a target nucleic acid molecule can hybridize to the complementary sequence and remove the complementary sequence. Thus, in some examples the biomolecule in a biomolecule-compound conjugate according to the present disclosure is a nucleic acid molecule, permitting specific binding between the nucleic acid molecule and a target protein, nucleic acid molecule, or other binding molecule, and removal of the molecule which binds to the nucleic acid molecule.

[0191] In one example, the target is a nucleic acid molecule, and the biomoleculecompound conjugate includes a nucleic acid molecule having a sequence of sufficient complementarity (sequence identity) to permit hybridization between the two nucleic acid molecules. For example, a nucleic acid molecule can have at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to at least a portion of a target nucleic acid molecule, such as this level of sequence identity over at least 30 contiguous nucleotides of the target, at least 40, at least 50, at least 75, at least 100, at least 500, at least 1000, or at least 10,000 contiguous nucleotides of the target or more.

[0192] In addition, protein-nucleic acid molecule interactions are well known in the art, and include those that control the structure and function of the nucleic acid molecule (DNA or RNA), such as transcription, translation, DNA replication, repair and recombination and RNA processing and translocation.

[0193] Compounds according to the present disclosure can be coupled with a nucleic acid via covalent bonds formed between a functional group of the nucleic acid and the biomolecule-binding moiety of the compound. In particular aspects, a nucleic acid is coupled4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 with the compound by coupling an amine group of the nucleic acid (e.g., an amine of a phosphoramidate group) with an activated ester of the compound.

[0194] Functional Nucleic Acids (FNAs)

[0195] In one example the biomolecule is a functional nucleic acid molecule (FNA) (Liu et al, Chem. Rev. 2009, 109, 1948- 1998). FNAs, including DNAzymes and DNA aptamers, are nucleic acid molecules (e.g.. DNA or RNA) that recognize and bind to a wide range of targets with high affinity and specificities. Thus, in some examples the biomolecule in a biomolecule-compound conjugate according to the present disclosure is an FNA, permitting specific binding between the FNA and a target, and removal of the target which binds to the FNA.

[0196] FNA sequences that can be modified or adapted to be used in the methods and biomolecule-compound conjugates provided herein, are known in the art (e.g., see US 8,058,415). One example of a FNA is a catalytic nucleic acid. The catalytic active nucleic acids can be catalytic DNA / RNA, also known as DNAzymes / RNAzymes, deoxyribozymes / ribozymes, DNA enzymes / RNA enzymes. Catalytic active nucleic acids can also contain modified nucleic acids. Aptazymes, RNAzymes, and DNAzymes become reactive upon binding an analyte by undergoing a chemical reaction (for example, cleaving a substrate strand of the FNA). In each instance, the outcome of the reactive polynucleotide becoming reactive is to cause disaggregation of the aggregate and the release of at least one oligonucleotide. Other example of a FNA is an aptamer, which undergoes a conformational change upon binding to the target. Aptamers become reactive upon binding an analyte by undergoing a conformational change.

[0197] FNAs can be selected from pools of DNA (usually 2~25 kDa) with ~1015 random sequences via a process known as in vitro selection or Systematic Evolution of Ligands by Exponential enrichment (SELEX). DNAzymes and aptamers exhibit specific catalytic activity and strong binding affinity, respectively, to various targets. The targets can range from metal ions and small organic molecules to biomolecules and even viruses or celis.

[0198] Methods of identifying a FNA that is specific for a particular target agent are routine in the art and have been described in several patents. For example US Patent Nos. 7,192,708; 7,332,283; 7,485,419; 7,534,560; and 7,612,185, and US Patent Publication Nos. 20070037171 and 20060094026, describe methods of identifying functional DNA molecules that can bind to particular ions, such as lead and cobalt. In addition, specific examples are4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 provided. Although some of the examples describe functional DNA molecules with fluorophores, such labels are not required for the methods described herein.

[0199] Aptamers are single stranded (ss) nucleic acids (such as DNA or RNA) that recognize targets with high affinity and specificity, which undergo a conformational change in the presence of their target. For example, the cocaine aptamer binds cocaine as its corresponding target. Thus, aptamers can be used as a biomolecule, / r? vitro selection methods can be used to obtain aptamers for a wide range of target molecules with exceptionally high affinity, having dissociation constants as high as in the picomolar range (Brody and Gold, J. Biotechnol. 74: 5-13, 2000; Jayasena, Clin. Chem., 45:1628-1650, 1999: Wilson and Szostak, Annu. Rev. Biochem. 68: 611 -647, 1999). For example, aptamers have been developed to recognize metal ions such as Zn(ll) (Ciesiolka et al., RNA 1 : 538-550, 1995) and Ni(ll) (Hofmann et al., RNA, 3:1289-1300, 1997); nucleotides such as adenosine triphosphate (ATP) (Huizenga and Szostak, Biochemistry, 34:656-665, 1995); and guanine (Kiga et al., Nucleic Acids Research, 26:1755-60, 1998); co-factors such as NAD (Kiga et al., Nucleic Acids Research, 26:1755-60, 1998) and flavin (Lauhon and Szostak, J. Am. Chem. Soc., 117:1246-57, 1995); antibiotics such as viomycin (Wallis et al., Chem. Biol. 4: 357-366, 1997) and streptomycin (Wallace and Schroeder, RNA 4:112-123, 1998); proteins such as HIV reverse transcriptase (Chaloin et al., Nucleic Acids Research, 30:4001 -8, 2002) and hepatitis C virus RNA-dependent RNA polymerase (Biroccio et al., J. Virol. 76:3688-96, 2002); toxins such as cholera whole toxin and staphylococcal enterotoxin B (Bruno and Kiel, BioTechniques, 32: pp. 178-180 and 182-183, 2002); and bacterial spores such as the anthrax (Bruno and Kiel, Biosensors & Bioelectronics, 14:457-464, 1999). Compared to antibodies, DNA / RNA based aptamers are easier to obtain and less expensive to produce because they are obtained in vitro in short time periods (days vs. months) and with limited cost. In addition, DNA / RNA aptamers can be denatured and renatured many times without losing their biorecognition ability.

[0200] DNA / RNAzymes typically contain a substrate strand that recognizes a target (and can include an RNA base) and a catalytic or enzyme domain. In some examples a co-factor, such as a metal ion, catalyzes substrate cleavage. For example, the lead DNAzyme binds lead as its corresponding target. Thus, DNA / RNAzymes can be used as specific binding agents. Aptazymes are the combination of aptamer and DNAzymes or ribozymes. Aptazymes work when the target binds to the aptamers which either triggers DNAzyme / ribozyme activities or inhibits DNAzyme / ribozyme activities. Thus, aptazymes can be used as biomolecules in biomolecule-compound conjugates according to the present disclosure.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0201] Compounds according to the present disclosure can be coupled with an FNA via covalent bonds formed between a functional group of the FNA and the biomolecule-binding moiety of the compound. In particular aspects, an FNA is coupled with the compound by coupling an amine group of the FNA (e.g., an amine of a phosphoramidate group) with an activated ester of the compound.

[0202] Biomolecule-compound conjugates according to the present disclosure can have structures satisfying any one of Formulas I, IA, IB, IA(i), IA(ii), I A(i)(a), IA(i)(b), IA(i)(c), IA(i)(d), IA(i)(e), IA(i)(f), IA(i)(g), IA(i)(h);IA(i)(i), IB(i), IB(ii), IB(i)(a);IB(i)(b), IB(i)(c), IB(i)(d), IIA, IIB, IIC, IIA(i), HA(ii), IIB(i), IIB(ii), IIC(i), IIC(ii), llC(iii), l!C(iv), wherein X is replaced with X', wherein X’ comprises the biomolecule bound to the compound. In some aspects, X’ is {Core}-linker-C(=O)-biomolecule>{CoreJ-linker-S-biomolecule, or {Core}-linker-NH- biomolecule. In some aspects, the biomolecule is an antibody.

[0203] Methods

[0204] Compounds of the present disclosure can be made according to methods described herein. In some aspects, the method comprises preparing a phthalocyanine core precursor compound having a structure according to Formula III, wherein R4is selected from halogen or a group having a structure according to a formula {Core]-(CR2)n-CFG, wherein “CFG" is a clickable functional group as described herein, “Core” represents the attachment to the phthalocyanine core, and R, R1a, R1b, R2a, R2b, R3a, R3b, R5, and n are as described herein for any of the preceding formulas. In some aspects, the halogen can be selected from Br, Cl, F, or I, with representative examples being Br or I. In some aspects, the CFG group is an azide or alkyne.Formula III

[0205] In particular aspects of the present disclosure, the phthalocyanine core precursor can be selected from the structures according to Formulas IIIA-IIIC, shown below. While4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 beta-position attachment is indicated for the R4groups of the below-structures, aspects of the present disclosure also contemplate compounds with alpha-attachment, unless otherwise indicated.Formula IIIC4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0206] in representative aspects of the disclosure, the phthalocyanine core precursor can be made using a phthalonitrile (or a naphthalene-2,3-dicarbonitrile) starting material comprising an R'’ group. The starting material is exposed to ammonia in the presence of methanol to form an RMunctionalized isoindoline-1 ,3-diimine (or an RMunctionalized 1 H- benzo[f]lsoindole-1.3(2H)-diimine) ring system, which can then be combined with one or more other isoindoline-1 ,3-diimine (or 1 H-benzo[f]isoindole-1 ,3(2H)-diimine) ring systems, which can comprise R1a, R2a, R3a, R1b, R2b, and R3bgroups as described herein, in the presence of SiCk and quinoline to form an SiCh-containlng complex. In some aspects, the SiCh-containing complex can be converted to the phthalocyanine core precursor comprising an amine-terminated alkoxy group (e.g., O-[CH)2]4NH2). In some other aspects, the SiCI2- containing complex can be converted to an Si(OH)2complex after treatment with sodium hydroxide or ammonia, which can then be converted to the phthalocyanine core precursor after treatment with an amine-terminated siioxy reagent (e.g., 3- (methoxydimethylsilyl)propan-l -amine, 3-(diethy!(methoxy)silyl)propan-1-amine, 3- (diisopropyl(methoxy)silyl)propan-1 -amine, or 3-(methoxydiphenylsilyl)propan-1 -amine). Representative examples of a method for making a phthalocyanine core precursor are shown below in Schemes 1 -12.4239-11 1829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 14239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 24239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 34239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 44239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 54239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 64239-11 1829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 74239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 84239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 104239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 124239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0207] After the phthalocyanine core precursor is obtained, it c-an be converted to the desired compound by performing a click chemistry reaction (wherein the phthalocyanine core precursor comprises an R4group that comprises a clickable functional group), or a palladium-catalyzed carbon-carbon cross coupling reaction (wherein the phthalocyanine core precursor comprises an R4group that is a halogen, such as bromo). Representative methods for making the compounds are illustrated below in Schemes 13-32. Conditions suitable for performing a click chemistry reaction are recognizable to those in the art with the benefit of the present disclosure. In some aspects, the click chemistry reaction comprises a copper-catalyzed azide-alkyne cycloaddition, such as described in Schemes 13-24. Conditions suitable for performing a palladium-catalyzed carbon-carbon cross coupling reaction also are recognizable to those in the art with the benefit of the present disclosure.In some aspects, the palladium-catalyzed carbon-carbon cross coupling is a Heck reaction, such as described in Schemes 25 and 27-32. in yet other aspects, the palladium-catalyzed carbon-carbon cross coupling is a Sonogashira reaction, such as described in Scheme 26.Scheme 134239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 154239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 174239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 194239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 214239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 234239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 274239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 284239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 294239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 304239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 314239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 32

[0208] Methods of using the compounds and biomolecule-compound conjugates according to aspects of the present disclosure also are described. The biomolecule-compound conjugates and / or compounds described herein can be used in in vivo, ex vivo, or in vitro methods. In particular aspects of the present disclosure, biomolecule-compound conjugates4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 disclosed herein can be used in methods for killing (or, in some instances, removing) a target, such as a ceil (e.g., a target ceil), a pathogen, or a combination thereof. The target can be present in a sample or in a subject. In some aspects wherein the biomoleculecompound conjugate is used to kill a target cell, the cell expresses a protein on its surface, such as a tumor-specific protein or an immune cell-specific protein, that can specifically bind to a biomolecule (e.g., an antibody) that is conjugated to a compound of the present disclosure. In some aspects of the disclosure wherein a compound is used to kill or remove a pathogen, the X group can be selected from a clickable functional group that is configured to react with a separate clickable functional group that is present on a biomolecule (e.g., a clickable functional group-labeled antibody or bacteria-specific protein), or it can be selected from a maleimide group. In some aspects, unwanted pathogens can be removed from a subject by using a biomolecule-compound conjugate according to the present disclosure, wherein the biomolecule component of the conjugate is a specific binding agent for the pathogen, such as a virus, fungus, parasite, bacterial cell and the like.

[0209] Any pathogen or microbe can be removed or isolated using the methods and biomolecule-compound conjugates provided herein. In some examples, a particular microbial cell or organism is removed, a particular spore, or a particular virus. Exemplary- target pathogens include, but are not limited to, viruses, bacteria, fungi, nematodes, and protozoa. A non-limiting list of pathogens that can be removed or isolated using the methods provided herein are provided below.

[0210] For example, target viruses include positive-strand RNA viruses and negative-strand RNA viruses. Exemplary target positive-strand RNA viruses include, but are not limited to: Picomaviruses (such as Aphthovlrldae [for example foot-and-mouth-disease virus (FMDV)J), Cardioviridae; Enteroviridae (such as Coxsackie viruses, Echoviruses, Enteroviruses, and Polioviruses); Rhinoviridae (Rhinoviruses)); Hepataviridae (Hepatitis A viruses); Togaviruses (examples of which include rubella; alphaviruses (such as Western equine encephalitis virus, Eastern equine encephalitis virus, and Venezuelan equine encephalitis virus)); Flaviviruses (examples of which include Dengue virus, West Nile virus, and Japanese encephalitis virus); Calciviridae (which includes Norovirus and Sapovirus); and Coronaviruses (examples of which include SARS coronaviruses, such as the Urbani strain). Exemplary negative-strand RNA viruses include, but are not limited to: Orthomyxyovi ruses (such as the influenza virus), Rhabdoviruses (such as Rabies virus), and Paramyxoviruses (examples of which include measles virus, respiratory syncytial virus, and parainfluenza viruses).

[0211] Viruses also include DNA viruses. Target DNA viruses include, but are not limited to: Herpesviruses (such as Varicella-zoster virus, for example the Oka strain;4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 cytomegalovirus; and Herpes simplex virus (HSV) types 1 and 2), Adenoviruses (such as Adenovirus type 1 and Adenovirus type 41 ), Poxviruses (such as Vaccinia virus), and Parvoviruses (such as Parvovirus B19).

[0212] Another group of viruses includes Retroviruses. Examples of target retroviruses include, but are not limited to: human immunodeficiency virus type 1 (HIV-1 ), such as subtype C; HIV-2: equine infectious anemia virus; feline immunodeficiency virus (FIV); feline leukemia viruses (FeLV); simian immunodeficiency virus (SIV); and avian sarcoma virus.

[0213] In one example, the virus detected with the disclosed methods or sensors is one or more of the following: HIV-1 (for example an HIV antibody, p24 antigen, or HIV genome); Hepatitis A virus (for example an Hepatitis A antibody, or Hepatitis A viral genome); Hepatitis B (HB) virus (for example an HB core antibody, HB surface antibody, HB surface antigen, or HB viral genome); Hepatitis C (HC) virus (for example an HC antibody, or HC viral genome); Hepatitis D (HD) virus (for example an HD antibody, or HD viral genome); Hepatitis E virus (for example a Hepatitis E antibody, or HE viral genome); a respiratory virus (such as influenza A & B, respiratory syncytial virus, human parainfluenza virus, or human metapneumovirus), or West Nile Virus.

[0214] Pathogens also include bacteria. Bacteria can be classified as gram-negative or gram-positive. Exemplary target gram-negative bacteria include, but are not limited to: Escherichia coli (e.g., K-12 and O157:H7), Shigella dysenteriae, and Vibrio cholerae. Exemplary target gram-positive bacteria include, but are not limited to: Bacillus anthracis, Staphylococcus aureus, Listeria, pneumococcus, gonococcus, and streptococcal meningitis. In one example, the bacteria removed with the disclosed methods and biomolecule-compound conjugates is one or more of the following: Group A Streptococcus; Group B Streptococcus; Helicobacter pylori; Methicillin-resistant Staphylococcus aureus; vancomycin-resistant enterococci; Clostridium difficile; E. coli (e.g., Shiga toxin producing strains): Listeria; Salmonella; Campylobacter; B. anthracis (such as spores): Chlamydia trachomatis; Ebola, and Neisseria gonorrhoeas.

[0215] Protozoa, nemotodes, and fungi are also types of pathogens. Exemplary target protozoa include, but are not limited to, Plasmodium (e.g., Plasmodium falciparum to diagnose malaria), Leishmania, Acanthamoeba, Giardia, Entamoeba, Cryptosporidium, Isospora, Balantidium, Trichomonas, Trypanosoma (e.g., Trypanosoma brucei), Naegleria, and Toxoplasma. Exemplary target fungi include, but are not limited to, Coccidiodes immitis and Blastomyces dermatitidis.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0216] In one example, bacterial spores are removed. For example, the genus of Bacillus and Clostridium bacteria produce spores that can be detected. Thus, C. botulinum, C. perfringens, B. cereus. and B. anthracis spores can be detected (for example detecting anthrax spores). One will also recognize that spores from green plants can also be removed using the methods and biomolecule-compound conjugates provided herein.

[0217] In some examples, intact microbes are removed, for example by binding to a target surface protein (such as a receptor) on the microbe using biomolecule-compound conjugates that include, for example, antibodies, DNAzymes, or DNA aptamers specific for the target protein. For example, antibodies that can be used with the disclosed methods and biomolecule-compound conjugates are available from commercial sources, such as Novus Bioiogicals (Littleton , CO) and ProSci Incorporated (Poway, CA) provide E. col / -specific antibodies: KPL (Gaithersburg, MD) provides Listeria-specific antibodies; Thermo Scientific / Pierce Antibodies (Rockford, IL) provides antibodies specific for several microbes, including bacteria and viruses,, such as influenza A, HIV-1 , HSV 1 and 2, E. coil, Staphylococcus aureus, Bacillus anthracis and spores thereof, Plasmodium, and Cryptosporidium. In addition, aptamers specific for microbial proteins can be used with the disclosed methods and biomolecule-compound conjugates, such as those specific for HIV reverse transcriptase (Chaloin et al., Nucleic Acids Research, 30:4001 -8, 2002) and hepatitis C virus RNA-dependent RNA polymerase (Biroccio eta / ., J. Virol. 76:3688-96, 2002); toxins such as cholera whole toxin and staphylococcal enterotoxin B (Bruno and Kiel, BioTechniques, 32: pp. 178-180 and 182-183, 2002); and bacterial spores such as anthrax (Bruno and Kiel, Biosensors & Bioelectronics, 14:457-464, 1999). In addition, DNAzymes specific for microbial proteins can be used with the disclosed methods and biomolecule- compound conjugates, such as those specific for Escherichia coli-K12 (Ali et al., Angewandte Chemie International Edition. 50, 3751-4, 2011 ; Li, Future Microbiol. 6, 973- 976, 2011 ; and Aguirre, et al., J. Visualized Experiments. 63, 3961 , 2012). Such molecules can be used to generate a biomolecule-compound conjugate to remove a target pathogen or spore.

[0218] The sample or the subject is contacted with a therapeutically effective amount of one or more biomolecule-compound conjugates or one or more compounds according to the present disclosure (for example in the presence of a pharmaceutically acceptable carrier, such as a pharmaceutically and physiologically acceptable fluid). In some aspects, contacting the sample or the subject comprises conditions that permit delivery of the biomolecule-compound conjugate or the compound to a target. For example, the biomolecule-compound conjugate or the compound can be present in a pharmaceutically4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 effective carrier, such as water, physiological saline, balanced salt solutions (such as PBS / EDTA), aqueous dextrose, sesame oil, glycerol, ethanol, combinations thereof, or the like, as a vehicle. The carrier and composition can be sterile, and the formulation suits the mode of administration.

[0219] After administering the one or more biomoiecule-compound conjugates or one or more compounds, the sample or the subject is irradiated. Irradiation can comprise irradiating the whole sample / subject or a targeted portion of the sample / subject. In particular aspects, irradiating comprises exposing a targeted portion of the sample or the subject to light. The targeted portion typically comprises the biomolecule-compound conjugate or the compound. In some aspects, irradiating can comprise applying an effective quantity of light sufficient to promote identifying the location of the biomolecule-compound conjugate or the compound within the sample or the subject and / or to detect and / or quantify killing of any target or target cell. In some such aspects, this can comprise applying an effective quantity of light sufficient to induce fluorescence of the biomolecule-compound conjugate or the compound. In some other aspects, irradiating can comprise applying an effective quantity of light sufficient to induce target (or target cell) killing. In some aspects, the light used for irradiation is infrared, near-infrared, or ultraviolet light. In particular aspects, the light is nearinfrared.

[0220] In some particular aspects, irradiation is carried out under conditions that permit killing of a target, for example irradiation at a wavelength of 650 nm to 1100 nm at a dose of at least 1 J cm2. In one example, there is at least 10 minutes, at least 30 minutes, at least 1 hour, at least 4 hours, at least 8 hours, at least 12 hours, or at least 24 hours (such as 1 to 4 hours, 30 minutes to 1 hour, 10 minutes to 60 minutes, or 30 minutes to 8 hours) in between contacting the cell with the biomolecule-compound conjugate (or the compound) and the irradiation. The NIR excitation light wavelength allows penetration of at least several centimeters into tissues. For example, by using fiber-coupled laser diodes with diffuser tips, NIR light can be delivered within several centimeters of otherwise inaccessible tumors located deep to the body surface. In addition to treating solid cancers, circulating tumor cells can be targeted since they can be excited when they traverse superficial vessels (for example using NIR LED wearable devices known to those in the art with the benefit of the present disclosure). The disclosed methods can also be used as a therapy for transplant rejection.

[0221] In some aspects, the method can also include contacting the target or target cell with one ar more additional therapeutic agents. In same aspects, there is a time-period following irradiation during which uptake of additional therapeutic agents can be enhanced.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025In some aspects of the disclosure, the time-period is approximately 8 hours after irradiation at a wavelength of 650 nm to 1100 nm at a dose of at least 10 J cm2, at least 20 J cm2, at least 30 J cm2, at least 40 J cm2, at least 50 J CUT2, at least 70 J cm-2, at least 80 J cm-2or at least 100 J cm2such as at least 10 to 100 J cm2. Thus, one or more additional therapeutic agents can be contacted with the cell contemporaneously or sequentially with the PIT. In one example, the additional therapeutic agents are administered after the irradiation, for example, about 0 to 8 hours after irradiating the cell (such as at least 10 minutes, at least 30 minutes, at least 60 minutes, at least 2 hours, at least 3 hours, at least 4, hours, at least 5 hours, at least 6 hours, or at least 7 hours after the irradiation, for example no more than 10 hours, no more than 9 hours, or no more than 8 hours, such as 1 hour to 10 hours, 1 hour to 9 hours 1 hour to 8 hours, 2 hours to 8 hours, or 4 hours to 8 hours after irradiation). In another example, the additional therapeutic agents are administered just before the irradiation (such as about 10 minutes to 120 minutes before irradiation, such as 10 minutes to 60 minutes or 10 minutes to 30 minutes before irradiation).

[0222] In some examples, combining the method according to the present disclosure with an additional therapy, enhances the effectiveness of the treatment of the tumor. For example, combining the disclosed method according to the present disclosure with the additional therapy can result in a tumor volume that is less than the tumor volume would be if it were treated with either the biomolecule-compound conjugate / PIT method according to the present disclosure alone or the additional therapy alone, that is, there is a synergistic effect. In one example, the volume of a tumor treated with the combination therapy is at least 2-fold, at least 3-fold, at least 4 -fold, or even at least 5-fold smaller than the volume of a tumor treated with either the disclosed method alone or the additional therapy alone (for example after at least 7 days, at least 10 days, at least 14 days, at least 30 days, at least 60 days, at least 90 days, or at least 120 days after the treatment). In one example, the volume of a tumor treated with the combination therapy is at least 5-fold, at least 6-fold, at least 7-fold, or even at least 10-fold smaller than the volume of a control untreated tumor (for example after at least 7 days, at least 10 days, at least 14 days, at least 30 days, at least 60 days, at least 90 days, or at least 120 days after the treatment). In another or additional example, combining the disclosed method with the additional therapy (such as anti-neoplastic agents) can increase the survival time of a subject having a tumor relative to the survival time of the subject if the tumor was treated with either the disclosed method alone or the additional therapy alone, that is, there is a synergistic effect. In one example, the survival time of a subject having a tumor treated with the combination therapy is at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, or at least 10-fold longer than survival time of a subject having a tumor treated with either the disclosed method alone or4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the additional therapy alone (for example after a specified period of time, such as at least 14 days, at least 30 days, at least 60 days, at least 90 days, at least 120 days, at least 6 months, at least 12 months, at least 24 months, or at least 5 years after the treatment, more subjects treated with the combination therapy will be alive than if treated with either therapy alone). In one example, the survival time of a subject having a tumor treated with the combination therapy is at least 5-fold, at least 10 -fold, at least 15-fold, or even at least 20- fold greater than the survival time of a subject having an untreated tumor (for example after at least 7 days, at least 10 days, at least 14 days, at least 30 days, at least 60 days, at least 90 days, at least 120 days after the treatment at least 6 months, at least 12 months, at least 24 months, or at least 5 years after the treatment, more subjects treated with the combination therapy will be alive than if untreated).

[0223] Exemplary additional therapeutic agents include anti-neoplastic agents, such as chemotherapeutic and anti-angiogenic agents or therapies, such as radiation therapy. In one example the agent is a chemotherapy immunosuppressant (such as Rituximab, steroids) or a cytokine (such as GM-CSF). Chemotherapeutic agents are known in the art (see for example, Slapak and Kufe, Principles of Cancer Therapy, Chapter 86 in Harrison’s Principles of Internal Medicine, 14th edition; Perry et al., Chemotherapy, Ch. 17 in Abeloff, Clinical Oncology 2nd ed., 2000 Churchill Livingstone, Inc; Baltzer and Berkery. (eds): Oncology Pocket Guide to Chemotherapy, 2nd ed. St. Louis, Mosby- Year Book, 1995; Fischer Knobf, and Durivage (eds): The Cancer Chemotherapy Handbook, 4th ed. St. Louis, Mosby-Year Book, 1993). Exemplary chemotherapeutic agents that can be used with the methods provided herein include but are not limited to, carboplatin, cisplatin, paclitaxel, docetaxel, doxorubicin, epirubicin, topotecan, irinotecan, gemcitabine, iazofurine, gemcitabine, etoposide, vinorelbine, tamoxifen, valspodar, cyclophosphamide, methotrexate, fluorouracil, mitoxantrone, Doxil (liposome encapculated doxiorubicine) and vinorelbine. In some examples, the additional therapeutic agent is conjugated to (or otherwise associated with) a nanoparticle, such as one at least 1 nm in diameter (for example at least 10 nm in diameter, at least 30 nm in diameter, at least 100 nm in diameter, at least 200 nm in diameter, at least 300 nm in diameter, at least 500 nm in diameter, or at least 750 nm in diameter, such as 1 nm to 500 nm, 1 nm io 300 nm, 1 nm to 100 nm, 10 nm to 500 nm, or 10 nm to 300 nm in diameter). Other therapeutic agents that can be used in combination with biomolecule-compound conjugates and / or compounds according to the present disclosure are as described in U.S. Pat. Pub. No. 2024 / 0101685, the relevant portion of which is incorporated herein by reference.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0224] The methods can be used to kill cells in vitro, for example by incubating cells of a sample with the biomolecule-compound conjugate or compound according to the present disclosure and, optionally, one or more therapeutic agents in culture, or in vivo, for example, by administering one or more biomolecule-compound conjugates or compounds and, optionally, one or more therapeutic agents to the subject. For example, a subject to be treated can be administered a therapeutically effective amount of one or more biomoleculecompound conjugates or compounds, followed by irradiating the subject (or a tumor or tumor cell in the subject) with a therapeutic dose of irradiation and administration of one or more additional therapeutic agents (such as within about 8 hours of the irradiation).

[0225] In one example, contacting target cells with one or more biomolecule-compound conjugates according to the present disclosure followed by irradiation and administration of an additional therapeutic agent kills the target cells that express a cell surface protein that specifically binds to the antibody of the biomolecule-compound conjugate. For example, the disclosed methods can kill at least 10%, for example at least 20%, at least 40%, at least 50%, at least 80%, at least 90%, or more of the treated cells relative to the absence of treatment with one or more biomolecule-compound conjugates followed by irradiation and optional administration of one or more therapeutic agents.

[0226] In one example, administration of one or more biomolecule-compound conjugates according to the present disclosure to a subject having a tumor, in combination with irradiation and optional administration of one or more therapeutic agents, kills the cells that express a cell surface protein that can specifically bind to the antibody, thereby treating the tumor. For example, the disclosed methods can decrease the size or volume of a tumor, slow the growth of a tumor, decrease or siow metastasis of the tumor (for example by reducing the number of metastases or decreasing the volume or size of a metastasis), or combinations thereof. For example, the disclosed methods can reduce tumor cell size or volume and / or a metastatic tumor cell volume (or number of metastatic tumors), such as by at least 10%, for example by at least 20%, at least 40%, at least 50%, at least 80%, at least 90%, or more, relative to the absence of administration of one or more biomoleculecompound conjugates followed by irradiation. In addition, the disclosed methods can result in a decrease in the symptoms associated with a tumor and / or a metastatic tumor, to one example, administration of the disclosed biomolecule-compound conjugates slows the growth of a tumor, such as by at least 10%, for example by at least 20%, at least 40%, at least 50%, at least 80%, at least 90%, or more, relative to the absence of administration of the biomolecule-compound conjugate followed by irradiation. Methods of monitoring tumor volume / size / metastasis are routine in the art. In some examples, the disclosed methods can4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 increase a subject’s (such as a subject with a tumor or who has had a tumor previously removed) survival time, for example relative the absence of administration of one or more biomolecule-compound conjugates, irradiation, and administration of one or more therapeutic agents, such as an increase of at least 20%, at least 40%, at least 50%, at least 80%, at least 90%, or more. For example, the disclosed methods can increase a subject’s survival time by at least 3 months, at least 6 months, at least 12 months, at least 18 months, at least 24 months, at least 36 months or more, relative to average survival time in the absence of administration of a biomolecule-compound conjugate, irradiation, and administration of one or more therapeutic agents.

[0227] Administration of therapeutically effective amounts of biomolecule-compound conjugates according to the present disclosure, followed by therapeutically effective doses of irradiation and optional administration of one or more therapeutic agents are capable of selectively killing tumor cells in vivo, and are capable of decreasing the weight or volume of a tumor in vivo. By selective killing of tumor cells relative to normal cells is meant that the methods are capable of killing tumor cells more effectively than normal cells such as, for example, cells not expressing the cell surface protein that specifically binds to the antibody administered.

[0228] The disclosed methods can be used to treat fixed tumors in the body as well as tumors in the circulation {e.g., leukemia cells, metastases, circulating tumor cells): however, circulating cells, by their nature, cannot be exposed to light for very long. Thus, if the cell to be killed is one that is circulating throughout the body, the methods can be accomplished by using a device that can be worn, or that covers parts of the body. Such devices are known to those in the art with the benefit of the present disclosure.

[0229] In some examples, the method further includes monitoring the therapy, such as killing of tumor cells. In such examples, the biomolecule-compound conjugate is contacted with the ceils and the ceils irradiated as described above. However, a lower dose of the biomolecule-compound conjugate and NIR light can be used (as cell killing may not be required, just monitoring of the therapy). In one example, the amount of biomoleculecompound conjugate administered for monitoring is at least 2-fold less (such as at least 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-fold less than the therapeutic dose). In one example, the amount of the biomolecule-compound conjugate administered for monitoring is at least 20% or at least 25% less than the therapeutic dose. In one example, the amount of NIR light used for monitoring is at least 1 / 1000 or at least 1 / 10,000 of the therapeutic dose. This permits detection of the cells being treated. For example, by using such methods, the size of the tumor and metastases can be monitored.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0230] In some examples, the method is useful during surgery, such as endoscopic procedures. For example, after the biomolecule-compound conjugate is contacted 'with the cells and the ceils irradiated as described above, this not only results in cell killing, but permits a surgeon or other medical care provider to visualize the margins of a tumor, and help ensure that resection of the tumor (such as a tumor of the skin, breast, lung, colon, or prostate) is complete and that the margins are clear. In some examples, a lower dose of the biomolecule-compound conjugate can be used for visualization, such as at least 2-fold less (such as at least 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-fold less than the therapeutic dose).

[0231] In some aspects of the present disclosure, the target cell can be a cell that is not desired or whose growth is not desired, such as a tumor cell. The cells can be growing in culture, or present in a mammal to be treated, such as a patient with cancer. Any target cell can be treated with aspects of the method according to the present disclosure. In one example, the target cell expresses a cell surface protein that is not substantially found on the surface of other normal (desired) cells, an antibody can be selected that specifically binds to such protein, and a biomolecule-compound conjugate generated for that protein. In one example, the cell surface protein is a tumor-specific protein. In one example, the cell surface protein is CD25, which can be used to target cells associated with undesired transplant rejection.

[0232] In one example, the tumor cell is a cancer cell, such as a cell in a patient with cancer. Exemplary cells that can be killed with the disclosed methods include cells of the following tumors: a liquid tumor such as a leukemia, including acute leukemia (such as acute lymphocytic leukemia, acute myelocytic leukemia, and myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia), chronic leukemias (such as chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia), polycythemia vera, lymphoma, Hodgkin’s disease, non-Hodgkin's lymphoma, multiple myeloma, Waldenstrdm's macroglobulinemia, heavy chain disease). In another example the cell is a solid tumor cell, such as sarcomas and carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, and other sarcomas, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, hepatocellular carcinomna, lung cancer, colorectal cancer, squamous cell carcinoma, basal ceil carcinoma, adenocarcinoma (for example adenocarcinoma of the pancreas, colon, ovary, lung, breast, stomach, prostate, cervix, or esophagus), sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, Wilms' tumor,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 cervical cancer, testicular tumor, bladder carcinoma, CNS tumors (such as a glioma, astrocytoma, medulloblastoma, craniopharyogioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma).

[0233] In some aspects of the present disclosure, the disclosed methods are used to treat a subject who has a tumor, such as a tumor described herein. In some examples, the tumor has been previously treated, such as surgically or chemically removed, and the disclosed methods are used subsequently to kill any remaining undesired tumor cells that may remain in the patient.

[0234] The disclosed methods can be used to treat any mammalian subject, such as a human, who has a tumor, such as a cancer, cr has had such previously removed or treated. Subjects in need of the disclosed therapies can include human subjects having cancer, wherein the cancer cells express a tumor-specific protein on their surface that can specifically bind to the biomolecule-compound conjugate. For example, the disclosed methods can be used as initial treatment for cancer either alone, or in combination with radiation or other chemotherapy. The disclosed methods can also be used in patients who have failed previous radiation or chemotherapy. Thus, in some examples, the subject is one who has received other therapies, but those other therapies have not provided a desired therapeutic response. The disclosed methods can also be used in patients with localized and / or metastatic cancer.

[0235] In some examples the method includes selecting a subject that will benefit from the disclosed therapies, such as selecting a subject having a tumor that expresses a cell surface protein (such as a tumor-specific protein) that can specifically bind to a biomoleculecompound conjugate according to the present disclosure. For example, if the subject is determined to have a breast cancer that expresses HER2, the subject can be selected to be treated with an anti-HER2-compound conjugate, and the subject subsequently irradiated as described herein.

[0236] In some aspects of the disclosure, the protein on the cell surface of the target cell to be killed is not present in significant amounts on other cells. For example, the cell surface protein can be a receptor that is only found on the target cell type.

[0237] In particular aspects of the present disclosure, the cell surface protein is a tumorspecific protein (also known in the art as a tumor-specific antigen), such as members of the EGF receptor family (e.g., HER1 , 2, 3, and 4) and cytokine receptors (e.g., CD20, CD25, IL-4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 202513R, CD5, CD52, etc.). Tumor specific proteins are those proteins that are unique to cancer cells or are much more abundant on them, as compared to other cells, such as normal cells. For example HER2 is primarily found in breast cancers, while HER1 is primarily found in adenocarcinomas, which can be found in many organs, such as the pancreas, breast, prostate, and colon.

[0238] Exemplary tumor-specific proteins that can be found on a target cell (and to which an antibody specific for that protein can be used to formulate a biomolecule-compound conjugate according to the present disclosure), include but are not limited to: any of the various MAGEs (Melanoma-Associated Antigen E), including MAGE 1 (e.g., GenBank Accession Nos. M77481 and AAA03229), MAGE 2 (e.g., GenBank Accession Nos. L18920 and AAA17729), MAGE 3 (e.g., GenBank Accession Nos. U03735 and AAA17446), MAGE 4 (e.g., GenBank Accession Nos. D32075 and A06841 .1 ), etc.: any of the various tyrosinases (e.g., GenBank Accession Nos. U01873 and AAB60319); mutant ras: mutant p53 (e.g., GenBank Accession Nos. X54156, CAA38095 and AA494311); p97 melanoma antigen (e.g., GenBank Accession Nos. M12154 and AAA59992): human milk fat globule (HMFG) associated with breast tumors (e.g., GenBank Accession Nos. S56151 and AAB19771 ); any of the various BAGEs (Human B melanoma-Associated Antigen E), including BAGE1 (e.g., GenBank Accession No. Q13072) and BAGE2 (e.g., GenBank Accession Nos. NM„182482 and NP__872288), any of the various GAGEs (G antigen), including GAGE1 (e.g., GenBank Accession No. Q13065) or any of GAGE2-6; various gangliosides, CD25 (e.g., GenBank Accession Nos. NP„ 000408.1 and NM_ 000417.2).

[0239] Other tumor-specific antigens include the HPV 16 / 18 and E6 / E7 antigens associated with cervical cancers (e.g., GenBank Accession Nos. NC_001526, FJ952142.1 , ADB94605, ADB94606, and U89349), mucin (MUG 1 )-KLH antigen associated with breast carcinoma (e.c?., GenBank Accession Nos. J03651 and AAA35756), CEA (carcinoembryonic antigen) associated with colorectal cancer (e.g., GenBank Accession Nos. X98311 and CAA66955), gp100 (e.g., GenBank Accession Nos. S73003 and AAC60634) associated with for example melanoma, MARTI antigens associated with melanoma (e.g., GenBank Accession No. NP-005502), cancer antigen 125 (CA125, also known as mucin 16 or MUC16) associated with ovarian and other cancers (e.g., GenBank Accession Nos. NM_024690 and NPjO78966): alpha-fetoprotein (AFP) associated with liver cancer (e.g., GenBank Accession Nos. NM...001134 and NP..001125); Lewis Y antigen associated with colorectal, biliary, breast, small-cell lung, and other cancers: tumor-associated glycoprotein 72 (TAG72) associated with adenocarcinomas; and the PSA antigen associated with prostate cancer (e.g., GenBank Accession Nos. X14810 and CAA32915).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0240] Other exemplary tumor-specific proteins further include, but are not limited to, PMSA (prostate membrane specific antigen: e.g... GenBank Accession Nos. AAA60209 and AAB81971 .1 ) associated with solid tumor neovasculature, as well prostate cancer; HER-2 (human epidermal growth factor receptor 2, e.g., GenBank Accession Nos. M16789.1 , Ml 6790.1 , M16791.1 , Ml 6792.1 and AAA58637) associated with breast cancer, ovarian cancer, stomach cancer and uterine cancer, HER-1 (e.g.. GenBank Accession Nos. NM_PO5228 and NP_005219) associated with lung cancer, anal cancer, and glioblastoma as well as adenocarcinomas; NY-ESO-1 (e.g. GenBank Accession Nos. U87459 and AAB49693) associated with melanoma, sarcomas, testicular carcinomas, and other cancers, hTERT (aka telomerase) (e.g., GenBank Accession. Nos. NM__198253 and NP_937983 (variant 1 ), NM__198255 and NP_937986 (variant 2)): proteinase 3 (e.g., GenBank Accession Nos. M29142, M75154, M96839, X55668, NM 00277, M96628, X56606, CAA39943 and AAA36342), and Wilms tumor 1 (WT-1 , e.g. GenBank Accession Nos. NM_000378 and NP 000369 (variant A), NM„024424 and NP. 077742 (variant B), NM 024425 and NP_077743 (variant C), and NM_024426 and NP_077744 (variant D)).

[0241] In one example the tumor-specific protein is CD52 (e.g., GenBank Accession. Nos. AAH27495.1 and GAI15846.1 ) associated with chronic lymphocytic leukemia; CD33 (e.g., GenBank Accession. Nos. NM_023068 and CAD36509.1 ) associated with acute myelogenous leukemia; and CD20 (e.g., GenBank Accession. Nos. NP__068769 NP_031667) associated with Non Hodgkin lymphoma.

[0242] In some examples, the tumor-specific protein or immune cell specific protein is or includes HER1 / EGFR, CTLA4, PD-L1 , mesothelin, PSMA, HER2 / ERBB2, CD3, CD18, CD20, CD25 (IL-2Ra receptor), CD30, CD33, CD44, CD52, CD133, CD206, CEA, AFP, Lewis Y, TAG72, VEGF, VEGFR, EpCAM, EphA2, glypican-1 , glypican-2, glypican-3, gpA33, a mucin (such as MUC1 , MUC4, MUC5AC, or cancer antigen 125 (CA125)), CAIX, a folate-binding protein, a ganglioside (such as GD2, GD3, GM1 or GM2), integrin aVp3, ERBB3, MET, IGF1 R, EPHA3, TRAILR1 , TRAILR2, RANKL, FAP, tenascin, BCR complex, gp72, HLA-DR 10p, HLA-DR antigen, IgE, CA 242, PEM antigen, SK-1 antigen, PD-1 , or PD-L2.

[0243] Overview of Several AspectsDisclosed herein are compounds having a structure according to Formula I or Formula II as described herein, wherein: X is a biomolecule-binding moiety or a precursor thereto; the Linker has a structure according to a formula {Core}-(CRa)n-Y-(Z)m- (CR2)P[O(CR2)t]q-{X], wherein {Core} represents attachment to the phthalocyanine core and4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025{X} represents attachment to X; each R, Independently for each occurrence, is selected from hydrogen, halogen, aliphatic, heteroaliphatic, or aromatic; Y is selected from (i) a functional group produced from a reaction between two clickable functional groups: (ii) -CH=CH-[Qjs-, wherein s is 1 or 0 and Q1is selected from aromatic or -C(=O)Y’- or -S(=O)2Y’„ wherein Y’ is NR" or O, wherein R." is H, -CN, CFs, or a sulfonyl group; or (iii) -C^C-Q2, wherein Q2is - (CH2)UC(=O)Y'-, wherein u is an integer selected from 1 to 10, Y’ is NR” or O, wherein R” is H, -CN, CF3, or a sulfonyl group; Z is a heteroatom; m is 1 or 0; each of n, p, and t independently is selected from an integer ranging from 0 to 50; and q is an integer selected from 0 to 50; G, if present, is selected from halogen (such as chloro, bromo, fluoro, or iodo) or Linker-X (wherein the linker group and the X group are selected from definitions provided herein); each of R'a, R2aR3a, R!b, R2b, and R3bindependently is selected from hydrogen, aliphatic, halogen, heteroaliphatic, aromatic, thiol, hydroxyl, or amine; or (i) R1aand Re join together, with the carbon atoms to which they are attached, to form a 6-membered aromatic ring, (ii) R2aand R2bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring, (iii) R3aand R3t!join together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring, or (iv) any combination of two or more of (i)-(iii); and L is selected from -(CH?),-, -Si(R5)2(CH»)r-, -C(=O)(CH?)r, or -PhfCH?),-, wherein each R5independently is aliphatic or aryl, r is an integer selected from 1 to 5 and wherein any CH2group of the L group is attached to the quaternary amine of Formula I or Formula II.

[0244] In any or all aspects, the compound has a structure according to Formula IA or Formula IB as described herein.

[0245] In any or all aspects, the compound has a structure according to any one of Formulas IA(i) - Formula IA(iv) as described herein, wherein ring A is a ring system selected from a phenyl ring, a pyridyl ring, a triazole, a cyclooctafdjpyridazine, a cycloocta[d|triazole, or a triazote-functionalized DBCO.

[0246] In any ar all aspects, the compound has a structure according to one of Formulas IA(i)(a), I A(i)(b), IA(i)(c), IA(i)(d), A(i)(e), IA(l)(f), IA(i)(g), I A(i)(h), or I A(i)(i) as described herein.

[0247] In any or all aspects, the compound has a structure according to Formula IB(i) or Formula IB(ii) as described herein, wherein ring A is a ring system selected from a phenyl ring, a triazole, a cycloocta[d]pyridazine, a cycloocta[d]triazoie, or a triazole-functionalized DBCO.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0248] In any or all aspects, the compound has a structure according to one of Formulas IB(i)(a), IB(i)(b), IB(i)(c), or IB(i)(d) as described herein.

[0249] In any or all aspects, G is present and is selected from chloro, bromo, fluoro, iodo, or Lmker-X, wherein the linker and X groups of Linker-X are as defined herein,

[0250] In any or all aspects, G is positioned ortho to the Linker-X group of Formula I.

[0251]

[0252] In any or all aspects, L is ■ (CHPL. -Si(Me)2(CH2)3-, ■Si(Et)2(CH2)3-, -Si(iPr)2(CH2)3-, or -Si(Ph)2(CH2)3-.

[0253] In any or all aspects, compound has a structure according to Formula II A, Formula IIB as described herein, wherein ring A is a ring system selected from a phenyl ring, a triazole, a cycloocta[d]pyridazine, a cycloocta[d|triazole, or a triazole-functionalized DBGO.

[0254] In any or all aspects, the compound has a structure according to one of Formulas IIA(i), IIA(ii), IIB(i), IIB(ii), IIC(i), HC(ii), IIG(iii), or IIC(lv) as described herein.

[0255] In any or all aspects, X is a biomolecule-binding moiety comprising an activated ester group.

[0256] In any or all aspects, the activated ester is an NHS ester.

[0257] In any or all aspects, X is a biomolecule-binding moiety precursor.

[0258] In any or all aspects, the biomolecule-binding moiety precursor is a carboxylic acid or a carboxylate.

[0259] In any or all aspects, X is a clickable functional group configured to react with a separate clickable functional group present on a bacteria-specific protein.

[0260] In any or all aspects, the clickable functional group is an alkyne or an azide.

[0261] In any or all aspects, Y comprises a ring formed between (I) an alkyne and an azide;(ii) a tetrazine and a trans-cyclooctene; (iii) an azide and a dibenzocyclooctyne (DBGO); or (iv) an azide and a bicyclo[6.1 .OJnonyne.

[0262] In any or all aspects, Y comprises a ring formed between an alkyne and an azide.

[0263] In any or all aspects, the ring formed between the alkyne and the azide is a triazole.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0264] In any or all aspects, m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR2)p-{X} or {Core}-(CR2)I1-Y-(CR2)p[O(CR2)t]q-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , q is an integer selected from 1 to 6, and Y is a 1 ,2,3-triazole.

[0265] In any or all aspects, m is 1 and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , Y is -CH=CH-Ph- or -CI-kCH-Pyridyl-, and m is 0.

[0266] In any or all aspects, m is 1 and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , Y is -CH=CH-Ph- or -CH^CH-Pyridyl-, Z is O, and m is 1 .

[0267] In any or all aspects, m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , and wherein Y is -CH=CH-C(==O)Y’ or -ChkCH- S(=O)2Y’, wherein Y’ is O or -NH, -N(CN), -NCF3, -NSO2Me, -NSO2CF3, -NSO2NH2, or - NSO2NMe2.

[0268] In any or all aspects, m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , and wherein Y is -C^C(CH2)2C(=O)NH-(CH2)t-, wherein t is an integer selected from 1 to 10.

[0269] In any or all aspects, each of n and m is zero and the Linker has a structure according to -CH=CH-(CR2)P-, -CH=CH-C(O)O-(CR2)P, or -CH=CH-C(O)NR"-(CR2)P-.

[0270] In any or all aspects, the compound is selected from any specific compound species disclosed herein.

[0271] In any or all aspects, the compound is conjugated to a biomolecule through the X group.

[0272] Also disclosed is a conjugate formed by coupling a biomolecule with a compound according to any or all of the above aspects, wherein the biomolecule becomes bound to the compound upon reaction between a functional group of the biomolecule and the X group of the compound.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0273] In any or all aspects, the biomolecule is an antibody.

[0274] In any or all aspects, antibody is a humanized antibody that specifically binds to a surface protein on a cancer cell.

[0275] Also disclosed is a method for treating a subject or sample using NIR-PIT, the method comprising: administering a compound according to any or all compound aspects, or a conjugate according to any or all conjugate aspects, or a pharmaceutically acceptable composition thereof, to the subject or the sample: and irradiating the conjugate by application of light to a targeted portion of the subject or the sample.

[0276] In any or all aspects, the light is applied (I) in a quantity sufficient to produce fluorescence of the conjugate, (ii) in a quantity sufficient to induce killing of a target or a target cell present in the subject or the sample, or a combination of (I) and (ii).

[0277] In any or all aspects, the light is light of a wavelength ranging from 650 nm to 1100 nm.

[0278] In any or all aspects, the light is applied at a dose of at least 1 J / cm2.

[0279] In any or all aspects, administering is carried out using intravenous administration.

[0280] In any or all aspects, the biomolecule of the conjugate is an antibody.

[0281] In any or all aspects, the subject or the sample comprises a cell comprising a surface protein selected from a tumor-specific protein or an immune cell-specific protein.

[0282] In any or all aspects, the subject or the sample comprises a bacterial species.

[0283] Also disclosed herein is a method of making a compound according to any or all of the above aspects, comprising: converting a phthalocyanine core precursor having a structure according to Formula III to the compound by performing a click chemistry reaction or a palladium-catalyzed carbon-carbon cross coupling reaction; wherein Formula III is as described herein and P.4is selected from halogen or a group having a structure according to a formula {Core]-(CR2)n-CFG, wherein CFG is a clickable functional group and “{Core}” represents attachment of R4to the phthalocyanine core precursor.

[0284] In any or all aspects, the phthalocyanine core precursor has a structure according to Formula IIIA, IIIB, or I IIC as described herein.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0285] hi any or all aspects, the click chemistry reaction comprises a copper-catalyzed azide-alkyne cycloaddition.

[0286] In any or all aspects, the palladium-catalyzed carbon-carbon cross coupling is a Heck reaction or a Sonogashlra reaction.

[0287] ExamplesExample 1

[0288] In this example, factors affecting the reaction for forming compounds of the present disclosure were evaluated by synthesizing silicon phthalocyanine dyes with various functional groups in various substitution positions (e.g., mono- / di-functional groups, such as methyl groups, methoxy groups and halogens, at a / p positions'). To identify an effective design and efficient synthetic processes of A3B-type asymmetric phthalocyanine dyes with the linker, silicon phthalocyanine dyes with sulfonate groups as axial ligands were synthesized as model compounds because these dyes can be purified with reverse-phase HPLC and are soluble in polar organic solvents, such as methanol. Therefore, these dyes can be characterized by NMR and MS (Schemes 33 and 34). Further, the quantitative analysis by peak area of HPLC can be performed.Scheme 334239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 34

[0289] Generai procedure for making Compounds 12-14: A dibromobenzene derivative (1 eq) and CuCN (5 eq) were dissolved in dimethylformamide (15 mL) and the mixture was stirred at 160 °C under an Ar atmosphere for 2.5-3 hours. After cooling, CH2CI2 was added4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 to the reaction mixture and the precipitate was filtered. After the filtrate was evaporated, CH2CI2 was added to the residue and the suspension was filtered. The filtrate was washed with H2O, dried over NazSCU, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product.

[0290] Compound 12: Yield, 70%. ’H NMR (400 MHz, CDCis): 6 2.63 (s, 3H), 7.57-7.66 (m, 3H). HRMS (ESI*) m / z: calcd for C9HsN2Na: 165.0423 [M+Na]T found: 165.0415.

[0291] Compound 13; Yield, 39%.1H NMR (400 MHz, CDCh): 63.92 (s, 3H), 7.19 (dd, J = 2.6, 8.7 Hz, 1 H). 7.27 (d, J - 2.6 Hz, 1 H), 7.72 (d, J - 8.7 Hz, 1 H). HRMS (ESI*) m / z: calcd for C9H6N2NaO: 181 .0372 [M+Na]7 found: 181 .0367.

[0292] Compound 14: Yield, 67%.1H NMR (400 MHz, CDCI3): 62.38 (s, 6H), 7.56 (s, 2H). HRMS (ESI+) m / z: calcd for CioH8NzNa: 179.0580 [M+Na]+; found: 179.0575.

[0293] Procedure for making Compound 15: 2.0 mol / 'L NH3 in MeOH (30 mL, 60 mmol) was added to compound 1 (1 .01 g, 6.92 mmol) and the mixture was stirred at 60 °C under an Ar atmosphere for 3 hours. After cooling, H2O was added to the reaction mixture. After MeOH was evaporated, the precipitate was collected, washed with H2O and dried. The filtrate was extracted with AcOEt and the organic layer was dried over NazSCU, filtered and evaporated. The crude product combined with the precipitate and the extract was purified with silica gel column chromatography to afford the pure product (0.243 g, 1 .49 mmol, y. 22%).1H NMR (400 MHz, CD3OD): 5 7.35 (ddd, J - 0.9, 7.8, 9.5 Hz, 1 H), 7.65 (dt, J - 4.5. 7.8 Hz, 1 H), 7.70 (td, J= 0.9, 7.8 Hz, 1 H). HRMS (ESP) m / z: calcd for C8H7FN3: 164.0619 [M+H]+: found: 164.0590.

[0294] Genera! procedure for making Compounds 16-25: 2.0 mol / L NH3in MeOH (10-100 mL) was added to the starting material (1 eq) and NaOMe (1 eq), and the mixture was stirred at 60 °C under an Ar atmosphere for 1 .5-6 hours. The solvent was evaporated, and the crude product was washed with H2O or purified with silica gel column chromatography to afford the pure product.

[0295] Compound 16: Yield, 97%.!H NMR (400 MHz, CD3OD): 57.62 (dd, J- 0.6, 4.1 Hz, 2H), 7.84 (t, 3= 4.1 Hz, 1 H). HRMS (ESI*) m / z: calcd for C8H7CIN3: 180.0323 [M+H]+; found: 180.0330.

[0296] Compound 17: Yield, 74%. ’H NMR (400 MHz, CD3OD): 62.66 (s, 3H), 7.39 (d, J = 7.5 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.67 (d, J - 7.5 Hz, 1 H). HRMS (ESP) m / z: calcd for C9H10N3: 160.0869 [M+H]+; found: 160.0877.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0297] Compound 18: Synthesized from compound 3. Yield, 42%.1H NMR (400 MHz, CDsOD): 54.03 (s, 3H), 7.49 (dd, J - 0.7, 7.7 Hz, 1 H), 7.54 (dd, J- 0.7, 8.8 Hz, 1 H), 7.79 (dd, J = 7.7, 8.8 Hz, 1 H). HRMS (ESI*) m / z: calcd for C9H10N30: 176.0818 [M+H]+; found: 176.0811.

[0298] Compound 19: Yield, 55%.1H NMR (400 MHz, CD3OD): 07.65 (d, J= 7.6 Hz, 1 H), 7.85 (d, 7.6 Hz, 1), 7.91 (s, 1 H). HRMS (ESH) m / z: calcd for CSH7CIN3: 180.0323[M+H]+; found: 180.0326.

[0299] Compound 20: Yield, 95%.!H NMR (400 MHz, CD3OD): 57.76 (dd,0.6, 8.0 Hz, 1 H), 7.80 (dd, 1.6, 8.0 Hz, 1 H), 8.05 (dd, 0.6, 1.6 Hz, 1 H). HRMS (ESP) m / z: calcd far C8H7BrN3: 223.9818 [M+H]*; found: 223.9830.

[0300] Compound 21: Yield, 99%. ’H NMR (400 MHz, CDjOD): 52.48 (s. 3H), 7.43 (qd, J= 0.7, 7.7 Hz, 1 H), 7.62 (t, J - 0.7 Hz, 1 H), 7.72 (d, J - 7.7 Hz, 1 H). HRMS (ESH) m / z: calcd for C9H10N3: 160.0869 [M+H]4; found: 160.0876.

[0301] Compound 22: Yield, 94%.1H NMR (400 MHz, CD3OD): 53.92 (s, 3H), 7.14 (dd, J = 2.1 , 8.4 Hz, 1 H), 7.48 (d, J = 2.1 Hz, 1 H), 7.76 (d, J = 8.4 Hz, 1 H). HRMS (ESI*) m / z: calcd for CaH!0N3O: 176.0818 [M+H]+; found: 176.0824.

[0302] Compound 23: Yield, 95%.1H NMR (400 MHz, CD3OD): 58.03 (s, 2H). HRMS (ESl y m / z: calcd for C8H6CI2N3: 213.9933 [M+H]+: found: 213.9899.

[0303] Compound 24: Yield, 63%. ’H NMR (400 MHz, CD3OD): 02.40 (s, 6H), 7.62 (s, 2H). HRMS (ESI*) m / z: calcd for C oH%4;:174.1026 [M+H]+; found: 174.1010.

[0304] Compound 25: Yield, 97%.!H NMR (400 MHz, CD3OD): 53.94 (s, 6H), 7.50 (s, 2H). HRMS (ESI*) m / z: calcd for CI0H12N3O2: 206.0924 [M+Hp; found: 206.0903.

[0305] General procedure for making Compounds 26-36, 42, and 91: A mono / di- substituted 1,3-diiminoisoindoline compound (1 mmol, 1 eq), 1 ,3-diiminoisoindoline (3 mmol, 3 eq) and SiCU (2 or 6 mmol, 2 or 6 eq) were dissolved in quinoline (3 mL) and the mixture was stirred at 210 °C under an Ar atmosphere for 2 hours. After cooling, 1 mol / L NaOHaq (3 mL) was added to the mixture and the reaction solution was stirred at 120 °C for 1 hour. The precipitate was collected, washed with MeOH and dried. The crude product was used for the next step without further purification.

[0306] Procedure for making Compound 39: Compound 37 (2.01 g, 17.9 mmol) and fumaronitrile (2.81 g, 35.9 mmol) were dissolved in CH2CI2 (20 mL) and boron trifluoride4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 diethyl ether complex (3.81 g, 26.9 mmol) w'as slowly dropped to the mixture. After the reaction solution was heated at 70CC under an Ar atmosphere, m-chloroperoxybenzoic acid (30% H2O, 8.91 g, 36.1 mmol) in CH2CI2(50 mL) was slowly added to the reaction solution over 40 minutes. Then, the solution was stirred at 70 °C for 1 hour. Saturated NaHCO3aq was added to the solution, following additional stirring for 10 minutes. The organic layer was separated, washed with H2O, dried over Na2SO4, filtered and evaporated. The residue and o-toluic acid (27 mg, 0.20 mmol) were dissolved in 1 ,2-dichloroethane (12 mL) and the mixture was irradiated with microwave (repeated 45 times in the following cycle: 140 °C, 60 s, 400 W / 100 °C, 10 s, 0 W). After that, the solvent was evaporated and the crude product was purified with silica gel column chromatography to afford the pure product (0.588 g, 3.76 mmol, y. 21%).1H NMR (400 MHz, CDCI3): 0 2.57 (s, 6H), 7.45 (s, 2H). HRMS (ESI+) m / z\ calcd for Ci0H,3N2Na: 179.0580 [M+Nap; found: 179.0574.

[0307] Procedure for making Compound 40: 2.0 mol / L NH3in MeOH (30 mL, 60 mmol) was added to compound 39 (0.474 g, 3.03 mol) and NaOMe (0.169 g, 3.12 mmol), and the mixture was stirred at 60 °C under an Ar atmosphere for 30 hours. The solvent was evaporated and the crude product was purified with silica gel column chromatography to afford the pure product (0.290 g, 1.67 mmol, y. 55%).1H NMR (400 MHz, CD3OD): 52.62 (s, 6H), 7.28 (s, 2H). HRMS (ESP) m / z: calcd for CI0H!2N3: 174.1026 [M+H]+; found: 174.0998.

[0308] General procedure making a / fi-X-SiPc-NH2compounds: A crude silicon phthalocyanine dihydroxide derivative (0.15 mmol, 1 eq) and (3- aminopropyl)dimethylethoxysilane (1 .5 mmol, 10 eq) were dissolved in pyridine (100 mL) and the mixture was stirred at 150 °C under an Ar atmosphere for 5 hours. After cooling, the solvent was evaporated and the residue was azeotropic dried with toluene. The crude product was suspended with H2O / EtOH = 2:1 solution or H2O / MeOH = 10:1 solution, washed and dried. The mixture of A4-type and A3B-type silicon phthalocyanines was used for the next step without further purification, if the generation of A3B-type silicon phthalocyanine was confirmed by NMR.10309] Genera! procedure for making a / fi-X-SiPc compounds: A mixture of A4- type and AsB-type silicon phthalocyanines (70-100 mg, 1 eq), 1 ,3-propanesultone (50 eq) and / Pr2EtN (65 eq) were dissolved in MeOH (5 mL) and the mixture was stirred at 50 °C under an Ar atmosphere for 27-31 hours. The reaction solution was concentrated and the residue was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording u / p-X-SiPc as a sodium salt. Repurification was performed as needed. In HPLC purification, the intermediate with the five axial ligands was also collected and4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 subjected to the same reaction again to afford additional a / p-X-SiPc. HPLC analysis of the reaction solution was performed 26.5 hours after the start of the reaction, and the production ratio of A4-type and A3B-type phthalocyanines was calculated from the peak area ratio at the wavelength of peak top of each compound.

[0310] a-CI-SiPc: Yield, 4.0% (4 steps). "H NMR (400 MHz, CD3OD): 0 -2.78 (s, 12H), -2.18 (t, J - 8.4 Hz, 4H), -0.85—0.77 (m, 4H), 1 .66-1 .74 (m, 12H), 2.03 (t, J = 8.0 Hz, 4H), 2.71 (t, J = 6.8 Hz, 12H), 2.77-2.82 (m, 12H), 8.44 (t, J= 7.5 Hz, 1 H), 8.48-8.55 (m, 7H), 9.69-9.71 (m, 1 H), 9.77-9.82 (m, 6H). HRMS (ESI") m / z: calcd for CsoHysCINiofeOsoSeSh: 806.1143 [M-2Na]2~; found: 806.1101.

[0311] a-Me-SiPc: Yield, 8.4% (4 steps).1H NMR (400 MHz, CD3OD): 5 -2.79 (s, 12H), -2.16 (t, J - 8.4 Hz, 4H), -0.93—0.84 (m, 4H), 1 .66-1 .74 (m, 12H), 2.01 (t, J= 8.3 Hz, 4H), 2.71-2.79 (m, 24H), 4.08 (s, 3H), 8.30 (d, J= 7.4 Hz, 1 H), 8.40 (t, J= 7.4 Hz, 1 H), 8.49-8.54 (m, 6H), 9.65-9.70 (m, 2H), 9.77-9.80 (m, 5H). HRMS (ESI") m / z: calcd for C6iH78NwNa202oS6Si3: 796.1416 [M-2Na]?-; found: 796.1370.

[0312] p-CI-SiPc: Yield, 7.4% (4 steps). ’H NMR (400 MHz, CD3OD): 0 -2.78 (s, 12H), -2.19 (t, J= 8.4 Hz, 4H), -0.86—0.77 (m, 4H), 1.67-1.74 (m, 12H), 2.02 (t, J= 8.2 Hz, 4H), 2.73 (t, J == 6.8 Hz, 12 H), 2.77-2.81 (m, 12H), 8.46 (dd, J = 1.8, 8.2 Hz, 1 H), 8.51-8.54 (m, 6H), 9.72 (dd, 0.5, 1 .8 Hz, 1 H), 9.73-9.80 (m. 7H). HRMS (ESI") m / z: calcd for C6oH75CINioNa202cS6Si3: 806.1143 [M-2Na]2-: found: 806.1095.

[0313] fi-Br-SiPc: Yield, 0.3% (4 steps).1H NMR (400 MHz, CD3OD): 6 -2.78 (s, 12H), -2.19 (t, u - 8.7 Hz, 4H), -0.85—0.77 (m, 4H), 1 .67-1 .74 (m, 12H), 2.02 (t, J = 8.2 Hz, 4H), 2.73 (t, J= 6.8 Hz, 12 H), 2.77-2.81 (m, 12H), 8.51-8.55 (m, 6H), 8.61 (dd, J = 1.7, 8.2 Hz, 1 H), 9.68 (dd, J - 0.4, 8.2 Hz, 1 H), 9.76-9.80 (m, 6H), 9.88 (dd, J - 0.4, 1 .7 Hz, 1 H). HRMS (ESI") m / z: calcd for CeoHysBrNwNaaOaoSeSig: 828.0890 [M-2Na]2~; found: 828.0841.

[0314] p-Me-SiPc: Yield, 9.0% (4 steps).1H NMR (400 MHz, CD3OD): 0 -2.79 (s, 12H), -2.15 (t, J - 8.4 Hz, 4H), -1.01—0.93 (m, 4H), 1 .67-1 .75 (m, 12H), 2.01 (t, J- 8.2 Hz, 4H), 2.75-2.79 (m, 24H), 3.13 (s, 3H), 8.36 (dd, J= 0.7, 7.9 Hz, 1 H), 8.50-8.53 (m, 6H), 9.6 (s, 1 H), 9.66 (d, J - 7.9 Hz, 1 H), 9.77-9.80 (m. 6H). HRMS (ESI ) m / z: calcd for C6 iH78Ni0Na202oS6Si3: 796.1416 [M-2Na]2-; found: 796.1371.

[0315] 0-diCI-SiPc: Yield, 3.9% (4 steps).1H NMR (400 MHz, CD3OD): 6 -2.77 (s, 12H), -2.21 (t, J = 8.4 Hz, 4H), -0.78—0.69 (m, 4H), 1 .66-1 .74 (m, 12H), 2.03 (t, J = 8.2 Hz, 4H), 2.71 (t, J - 6.7 Hz, 12H), 2.78-2.82 (m, 12H), 8.52-8.55 (m, 6H), 9.76-9.80 (m, 6H), 9.88 (s,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20252H). HRMS (ESI-) m / z\ calcd for CBoHzaCIsNwNazOzoSsSis: 823.0948 [M~2Na]2~; found: 823.0906.

[0316] fi-diMe-SiPc: Yield, 5.5% (4 steps)2.79 (s, 12H), -2.11 (t, 8.4 Hz, 4H), -1.04—0.96 (m, 4H), 1 .68-1 .76 (m, 12H), 2.01 (i, J- 8.1 Hz, 4H),2.75-2.79 (m, 24H), 3.04 (s, 6H), 8.49-8.52 (m, 6H), 9.56 (s, 2H), 9.76-9.80 (m, 6H).HRMS (ESI“) m / z\ calcd tor C^HseNioNaaCboSeSia: 803.1494 [M-2Na]2“: found: 803.1452.

[0317] a-diMe-SiPc: Yield, 3.5% (4 steps).1H NMR (400 MHz, CD3OD): 6 -2.78 (s, 12H), -2.19 (t, J - 8.4 Hz, 4H), -0.86—0.78 (m, 4H), 1.64-1.72 (m, 12H), 2.01 (t, J = 8.2 Hz, 4H), 2.69 (t, J= 6.8 Hz, 12H), 2.75-2.80 (m, 12H), 4.05 (s, 6H), 8.19 (s, 2H), 8.49-8.51 (m, 6H), 9.65-9.67 (m, 2H), 9.77-9.80 (m, 4H). HRMS (ESI-) m / z: calcd for CezHsoNwNaaOaoSeSis: 803.1494 [M-2Na]?--; found: 803.1449.

[0318] As a result of the analysis of the reaction products, A3B-type asymmetric phthalocyanine dyes were prepared, with some specific examples exhibiting a level of decomposition (labeled as “decomp” in Table 1 ).

[0319] In some examples, phthalocyanine dyes with a-fluoro and a / p-methoxy groups exhibited levels of decomposition, whereas phthalocyanine dyes with a-CI, a-Me, p-CI, p-Br and a / p-methyl groups were successfully synthesized. Without being limited to a single theory, it currently is believed that these results suggests that: (i) an alkylated conjugation linker would be tolerated by the harsh conditions used for the phthalocyanine ring condensation reaction: and (ii) a synthetic route of linker extension by coupling reaction using p-brominated phthalocyanines as a starting material would be effective.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Example 2

[0320] With the above concepts determined in Example 1 in mind, various AgB-type asymmetric phthalocyanine dyes with linker groups were designed. In some examples, A3B- type asymmetric phthalocyanine compounds with an alkyne directly conjugated to the ring (compound 49 in Scheme 35) was synthesized. From this compound, synthesis of various compound species with linkers of various lengths having either a carboxylic acid (or a carboxylate) or NHS ester terminus was achieved using click chemistry reactions (Scheme 35).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 35

[0321] Compound 45 was made using the general procedure described in Example 1 .Compound 45: Yield,1.16 (s, 21 H), 7.68 (dd, J- 1.3,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20257.8 Hz, 1 H), 7.84 (dd, J= 0.8, 7.8 Hz, 1 H), 7.98 (dd, J = 0.8, 0.13 Hz, 1 H). HRMS (ESP) m / z: calcd for Ci9H27N3NaSi: 348.1867 [M+Na]+; found: 348.1855.

[0322] Procedure for making Compound 44: Compound 43 ( 1.56 g, 6.16 mmol), (triisopropy!siiy!)acety!ene (2.25 g, 12.3 mmol), PdCI2(PPh3)j (94 mg, 0.13 mmol), Cui (120 mg, 0.63 mmol) and NEts (1 .27 g, 12.6 mmol) were dissolved in tetrahydrofuran (25 mL) and the mixture was stirred at room temperature for 13 hours. Then, saturated NH4C!aq was added to the reaction mixture, which was extracted with AcOEt. The organic layer was washed with saturated NaClaq, dried over NasSCu, filtered and evaporated. The crude product was purified with silica gei column chromatography to afford the pure product (1 .84 g, 5.97 mmol, y. 97%).1H NMR (400 MHz. CDCh): 5 1.12-1.15 (s. 21 H), 7.73-7.78 (m. 2H). 7.85 (dd, J- 0.8, 1.4 Hz, 1 H). HRMS (ESP) m / z: calcd for Ci9H24N2NaSi: 331 .1601 [M+Na]4: found: 331 .1591 .

[0323] General procedure for making Compound 46: An a / p-substituted 1 ,3- diiminoisoindoline derivative (1 eq), 1 ,3-diiminoisoindoline (3 eq) and SiCU (6 eq) were dissolved in quinoline (1 .5-8 mL) and the mixture was stirred at 210 °C under an Ar atmosphere for 2 hours. After cooling, NH4OH (5-30 mL) was added to the mixture and the reaction solution was stirred at 80 °C for 1 hour. The precipitate was collected, washed 'with MeOH and dried. The crude product was used for the next step without further purification.

[0324] General procedure for making Compound 47: A crude silicon phthalocyanine dihydroxide derivative (1 eq) and (3-aminopropyl)dimethylethoxysilane (10 eq) were dissolved in pyridine (100-250 mL) and the mixture was stirred at 150 °C under an Ar atmosphere for 5-8 hours. After cooling, the solvent was evaporated and the residue was azeotropic dried with toluene. The crude product was suspended with H2O / MeOH = 10:1 solution, washed and dried. The crude product was used for the next step without further purification.

[0325] General procedure for making Compound 48: A crude phthalocyanines (1 eq), 1 ,3- propanesultone (50 eq) and / Pr2EtN (50-65 eq) were dissolved in MeOH (7-25 mL) and the mixture was stirred at 50 °C under an Ar atmosphere for 27-28 hours. The reaction solution was concentrated and the residue was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the pure product as a sodium salt. In HPLC purification, the intermediate with the five axial ligands was also collected and subjected to the same reaction again to afford additional product.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0326] Compound 48: Yield, 6.8% (4 steps).1H NMR (400 MHz. CD3OD): 6 -2.77 (s, 12H), -2.19 (t, J =- 8.4 Hz, 4H), -0.83—0.75 (m, 4H), 1.36 (s, 21 H), 1.66-1.74 (m, 12H), 2.03 (t, J = 8.2 Hz, 4H), 2.73 (t, J = 6.7 Hz, 12H), 2.76-2.81 (m, 12H), 8.49-8.54 (m, 7H), 9.71 (t, J = 1.0 Hz, 1 H), 9.73-9.80 (m, 7H). HRMS (ESH) m / z: calcd for C-i HgeNioNazOzoSeSi^ 879.2005 [M-2Na]2~; found: 879.1961.

[0327] Genera! procedure for making Compound 49: An A3B-type silicon phthalocyanine with triisopropylsily! group (1 eq) and AgF (10 eq) were dissolved in MeOH (3-8 mL), and the mixture was stirred at room temperature under an Ar atmosphere in the dark for 2-18.5 hours. Then, saturated NFUCIaq (3 mL) was added to the reaction solution, following additional stirring for 10 minutes. The reaction solution was concentrated and the residue was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the pure product as a sodium salt.

[0328] Compound 49: Yield, 83%. ’H NMR (400 MHz, CD3OD): 5 -2.78 (s, 12H), -2.17 (t, J - 8.4 Hz, 4H), -0.88—0.80 (m, 4H), 1.67-1.74 (m, 12H), 2.02 (t, J- 8.2 Hz, 4H), 2.72-2.81 (m. 24H), 4.09 (s, 1 H), 8.51-8.55 (m, 7H), 9.74-9.80 (m, 8H). HRMS (ESI") m / z: calcd for C62H76NwNa202oS6Si3: 801.1338 [M-2Na]2~; found: 801.1296.

[0329] Genera! procedure for dick reaction installation of linker group: An AgB-type si licon phthalocyanine with alkyne (1 eq), azido compound (3 eq), tris[(1 -benzyl-1 H-1 ,2,3-triazol-4- yl)methyl]amine (0.1 eq), CuSO4 (5 eq) and sodium ascorbate (10 eq) were dissolved in H2O / ffiuOH / CH3CN (2:2:1 ), and the mixture was stirred at room temperature in the dark for 5.5-19.5 hours. The crude product was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the pure product as a sodium salt.

[0330] p-Tz-IH700C2COOH: Yield, 80%.1H NMR (400 MHz, CD3OD): 6 -2.76 (s, 12H), -2.15 (t, J - 8.4 Hz, 4H), -0.88—0.81 (m, 4H), 1 .67-1 .74 (m, 12H), 2.03 (8.1 Hz, 4H),2.72-2.81 (m, 24H), 5.26 (s, 2H), 8.51-8.54 (m, 6H), 9.01 (dd, J= 1.3, 8.0 Hz, 1 H), 9.05 (s, 1 H), 9.78-9.82 (m, 7H), 10.20 (dd, J = 0.7, 1.3 Hz, 1 H). HRMS (ESI") m / z: calcd for CsiHyaNuNasOzsSeSh: 862.6360 [M-2Na]2”; found: 862.6313.

[0331] P-TZ-IR7QOC3COOH: Yield, 94%.1H NMR (400 MHz, CD3OD): 5 -2.76 (s, 12H), -2.15 (t, 8.3 Hz, 4H), -0.88—0.80 (m, 4H), 1 .67-1 .74 (m, 12H), 2.03 (t, J= 8.1 Hz, 4H),2.72-2.81 (m, 24H), 3.02 (t, J - 7.2 Hz, 2H), 4.91 (t, J - 7.3 Hz, 2H), 8.52-8.54 (m, 6H), 8.984239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025(dd, J= 1.3, 8.0 Hz, 1 H), 9.09 (s, 1 H), 9.78-9.82 (m, 7H), 10.17 (s, 1 H). HRMS (ESI") m / z: calcd for C6sH8oNi3Na3022S6Si3: 869.6439 [M-2Na]2“; found: 869.6394.

[0332] p-Tz-iR700C3SE: HRMS (ESI") m / z: calcd for Ce9H84Ni4Na2O24S6SI3: 907.1611 [M-2Na]2": found: 907.1563.

[0333] p-Tz lR700C6COOH: Yield, 65%.1H NMR (400 MHz, CD3OD): 6 -2.76 (s, 12H), -2.14 (t, J - 8.4 Hz, 4H), -0.93—0.85 (m, 4H), 1 .57-1 .63 (m, 2H), 1.67-1.74 (m, 12H), 1.78-1.85 (m, 2H), 2.02 (t,8.2 Hz, 4H), 2.17-2.25 (m, 2H), 2.29 (t, J = 7.4 Hz, 2H), 2.73-2.80 (m, 24H), 4.69 (t, J= 7.4 Hz, 2H), 8.52-8.54 (m, 6H), 9.01 (dd, J= 1.4, 8.0 Hz, 1 H), 9.17 (s, 1 H), 9.78-9.83 (m, 7H), 10.19 (s, 1 H). HRMS (ESI") m / z: calcd for CegHseNisNasO^SeSh: 890.6673 [M-2Na]2-; found: 890.6628.

[0334] P-TZ-IR700C6SE: HRMS (ESI") m / z: calcd for C72H9c.Ni4Na2O24S6Si3: 928.1845 [M-2Na]2"; found: 928.1797.

[0335] I3-TZ-IR700C10COOH: Yield, 84%.1H NMR (400 MHz, CD3OD): 6 -2.76 (s, 12H), -2.12 (t, J= 8.4 Hz, 4H), -0.97—0.88 (m, 4H), 1 .38-1 .45 (m, 6H), 1.50-1.57 (m, 4H), 1.63- 1.75 (m, 14H), 2.02 (t, J= 8.2 Hz, 4H), 2.16-2.24 (m, 4H), 2.74-2.80 (m, 24H), 4.68 (t, J = 7.3 Hz, 2H), 8.52-8.55 (m, 6H), 9.03 (dd, J= 1.4, 8.0 Hz, 1 H), 9.20 (s, 1 H), 9.78-9.87 (m, 7H), 10.19 (s, 1 H). HRMS (ESI") m / z: calcd for Czj'H^NisNa^SsSis: 918.6986 [M-2Na]2~; found: 918.6943.

[0336] p-Tz-IR700C10SE: HRMS (ESI") m / z: calcd for CyeHgaNuNazG^SeSh: 956.2158 [M-2Na]2"; found: 956.2110.

[0337] General procedure for making succinimidyl ester compounds: An A3B -type silicon phthalocyanine with carboxylate at the end of linker (1 eq), di(W-succinimidyl) carbonate (50 eq) and excess NEt3were dissolved in dimethyl sulfoxide, and the mixture was stirred at room temperature under an Ar atmosphere in the dark for 6-16 hours. Then, Et2O was added to the reaction solution to generate the precipitate, which was collected and dried. The product was used for the antibody labeling without further purification. If the succinimidyl ester compounds were not or not easily formed in this condition, HATU, AA hydroxysuccinimide and / PrzEtN were used instead of di(A / -succinimidyl) carbonate and NEt3.

[0338] General procedure for making Compounds 57 and 59: A bromofatty acid compound (1 eq) and NaN3(1.1 eq) were dissolved in dimethyl sulfoxide (20 mL), and the mixture was stirred at room temperature under an Ar atmosphere for 13.5-14 hours. After addition of4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025H2O, the reaction mixture was extracted with AcOEt. The organic layer was washed with H2O and saturated NaClaq, dried over Na2SO4, filtered, evaporated and dried. The product was used for the next step without further purification.

[0339] Compound 57: Yield, 66%. ' H NMR (400 MHz, CD3OD): 5 2.55 (t, J = 6.3 Hz, 2H), 3.54 (t, J = 6.3 Hz, 2H). HRMS (ESI-) m / z: calcd for C3H4N3O2: 114.0309 [M-H]-; found: 1 14.0298.

[0340] Compound 59: Yield, 97%.1H NMR (400 MHz, CD3OD): 5 1 .34-1 .40 (m, 10H),1 .55-1 .62 (m, 4H), 2.28 (t, 7.4 Hz, 2H), 3.28 (t, J= 6.9 Hz, 2H). HRMS ( ESI") m / z: calcd for CI0H1SN3O2: 212.1405 [M-H]-; found: 212.1399.

[0341] General procedure for making Compounds 50-53: An azido fatty acid compound (1 eq) and NaHCOs (1 eq) were dissolved in H2O (10 mL), and the mixture was stirred at room temperature for 10 minutes. Then, the solvent was evaporated and the residue was dried. The product was used for the next step without further purification.

[0342] Compound 50: Yield 95%.!H NMR (400 MHz, CD3OD): 5 3.65 (s, 2H). HRMS (ESH) m / z: calcd for CzHjNsNasCh: 145.9937 [M+Nap; found: 145.9928.

[0343] Compound 51: Yield, 96%.!H NMR (400 MHz, CD3OD): 5 2.40 (t, J = 6.9 Hz, 2H), 3.49 (t, J = 6.9 Hz, 2H). HRMS (ESH) m / 2: calcd for C3H4N3Na2O2: 160.0093 [M+Na]+; found: 160.0085.

[0344] Compound 52: Yield, 96%.1H NMR (400 MHz, CD3OD): 5 1 .37-1 .45 (m, 2H), 1 .57-1 .66 (m, 4H), 2.16 (t, J = 7.6 Hz, 2H), 3.28 (t, J - 7 0 Hz, 2H). HRMS (ESH) m / z: calcd forCsHioNsNasOj: 202.0563 [M+Na]+; found: 202.0555.

[0345] Compound 53: Yield, 97%.1H NMR (400 MHz, CD3OD): 6 1 .33-1 .40 (m, 10H), 1 .55-1 .61 (m, 4H), 2.15 (t, J = 7.6 Hz, 2H), 3.27 (t, J = 6.9 Hz, 2H). HRMS (ESH) m / z: calcd for C10H.8N3Ng.2O2: 258.1 189 [M+Na]+; found: 258.1 180.Example 3

[0346] in this example, compounds comprising a terminal azide (N3) group were prepared according to the methods described below and as summarized in Scheme 36.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 36

[0347] Procedure for making Compound 61: Compound 60 (1.22 g, 4.06 mmol) and NaNs (1.02 g, 15.8 mmol) were dissolved in dimethylformamide (6 mL), and the mixture was stirred at room temperature under an Ar atmosphere for 12 hours. Then, H2O was added to the reaction solution, which was extracted with CH2CI2. The organic layer was washed with H2O, dried over NazSCU, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (0.796 g, 3.55 mmol, y. 87%). 'H NMR (400 MHz, CDCI3): 5 1.30-1.38 (m, 12H), 1.56-1.63 (m, 4H), 3.26 (t, J ■-= 7.0 Hz, 4H).

[0348] Procedure for making P-TZ-IR7OOCION3: Compound 49 (4.5 mg, 2.7 pmol), compound 61 (8.0 mg, 36 pmol), tris[(1 -benzyl- 1 H-1 ,2,3-triazol-4-y1)methyl]amine (0.7 mg, 1 .3 pmol), CUSO4-5H2O (3.8 mg, 15 pmol) and sodium ascorbate (6.2 mg, 31 pmol) were dissolved in HgO / ffiuOH / CHsCN (0.3 mL / 0.3 mL / 0.15 mL), and the mixture was stirred at room temperature in the dark for 12.5 hours. The crude product was purified with reversephase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the pure product as a sodium salt (4.2 mg, 2.2 pmol, y. 82%).1H NMR (400 MHz, CD3OD): 5 -2.76 (s, 12H), -2.14—2.10 (m, 4H), -0.97—0.87 (m, 4H), 1.40-1.45 (m, 8H), 1.52-1.62 (m, 6H), 1.67-1.75 (m, 12H), 2.02 (t, J= 8.3 Hz, 4H), 2.16-2.22 (m, 2H), 2.74-2.80 (m, 24H), 3.28 (t, J- 6.9 Hz, 2H), 4.69 (t, J = 7.2 Hz, 2H), 8.51-8.55 (m, 6H), 9.05 (dd,1.4, 8.0 Hz, 1 H), 9.24 (s, 1 H), 9.78-9.81 (m, 5H), 9.83-9.88 (m, 2H), 10.19 (s, 1 H). HRMS (ESI”) m / z: calcd for C?2H3.3N!6Na202oS3Sis: 913.2213 [M-2Na]2-; found: 913.2171 .Example 4

[0349] In this example, compounds with a terminal alkyne were synthesized, the terminal alkyne providing a clickable functional group for preparing the linker group. The alkyne was then reacted with a coupling partner comprising another clickable functional group (an azide)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 to provide a compound with a triazole-based linker. The methods used for this example are detailed below and summarized in Scheme 37.Scheme 374239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 37 (continued)

[0350] General procedure for making Compound 63: A dibromotoluene derivative (1 eq), N- bromosuccinimide (1 eq) and benzoyl peroxide (75% in H2O, 0.2 eq) were dissolved in CCI4 (10—15 mL), and the mixture was stirred at 80 °C under an Ar atmosphere for 2.5 hours.Then, 10% NaHCOsaq was added to the reaction solution, which was extracted with CH2CI2. The organic layer was dried over NasSCL, filtered and evaporated. The residue was purified with silica gel column chromatography to afford the product.

[0351] Compound 63: Compound 63 could not be separated from the dibromo compound by column purification. The purity was about 80%. The mixture was used for the next step.NMR (400 MHz, CDCb): 5 4.38 (s, 2H), 7.19 (dd, J= 2.1 , 8.2 Hz, 1 H), 7.59 (d, J = 8.2 Hz, 1 H), 7.65 (d, J- 2.1 Hz, 1 H).

[0352] General procedure for making Compounds 64: 1 .6 mol / L nBuLi (in hexane, 1-1 .5 eq) was slowly dropped to (trilsopropy!silyl)acetylene (1—1.5 eq) in tetrahydrofuran (6 mL) at ~78 °C under an Ar atmosphere, and the mixture was stirred at --78 °C for 1 .5 hours. A benzyl bromide derivative (1 eq) dissolved in tetrahydrofuran (2 mL) was added to the reaction mixture, which was stirred at -78 °C for 30 minutes. The reaction mixture was further stirred at room temperature for 1 hour, as needed. The solution was evaporated, and the residue was purified with silica gel column chromatography to afford the product.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0353] Compound 64: Compound 64 could not be separated from the by-products by column purification. The purity was about 70%. The mixture was used for the next step. ^ H NMR (400 MHz, CDCI3): 6 1.00-1.03 (m, 21 H), 2.54 (t, J = 7.0 Hz, 2H), 2.77 (t, J= 7.0 Hz, 2H), 7.05 (dd, J - 2.1 , 8.2 Hz, 1 H), 7.50-7.52 (m, 2H).

[0354] Procedure for making Compound 65: Deoxygenated dimethylacetamide (1 mL) was added to a crude compound 64 (199 mg), Zn(CN)2(81 .7 mg, 0.70 mmol), Rd2(dba)3(10.8 mg, 12 pmol) and 1 ,1 ’-bis(diphenylphosphino)ferrocene (9.9 mg, 18 pmol) under an Ar atmosphere, and the mixture was stirred at 120 °C for 2 hours. Then, CH2CI2 was added to the reaction solution and the precipitate was filtered. The filtrate was evaporated and the crude product was purified with silica gel column chromatography to afford the pure product (78.8 mg, 0.23 mmol).1H NMR (400 MHz, CDCI3): 5 0.99-1 .03 (m, 21 H), 2.63 (t,6.8 Hz,2H), 2.94 (t, J = 6.8 Hz, 2H), 7.62 (dd, J= 1.6, 8.1 Hz, 1 H), 7.72-7.74 (m, 2H). HRMS (ESH) m / z: calcd for C2iH2eN2NaSi : 359.1914 [M+Na]+: found: 359.1904.

[0355] Compound 66 was made using the general procedure described in Example 1 . Compounds 67, 68, 69, 70, 71 , 73, and p-TzEt-IR700C8COOH were made according to the procedure described by Example 2. p-TzEt-IR700C8SE was made according to the general procedure for making the succinimidyl ester compounds described in Example 2.

[0356] Compound 66: Yield, 89%. ’H NMR (400 MHz, CDSOD): 6 0.92-0.97 (s, 21 H), 2.68 (t, J = 7.0 Hz, 2H), 2.98 (t, J - 7.0 Hz, 2H), 7.54 (dd, J - 1 4, 7.7 Hz, 1 H), 7.75 (d, J == 1 .4 Hz, 1 H), 7.78 (d, J = 7.7 Hz, 1 H). HRMS (ESI*) m / z: calcd for C2i H32N3Si: 354.2360 [M+H]+; found: 354.2353.

[0357] Compound 69: Yield, 4.6% (4 steps).1H NMR (400 MHz, CD3OD): 3 -2.78 (s, 12H), -2.15 (t, J - 8 4 Hz, 4H), -0.98—0.90 (m, 4H), 1 .01 (s, 21 H), 1.67-1.75 (m, 12H), 2.01 (t, J = 8.2 Hz, 4H), 2.74-2.80 (m, 24H), 3.12 (t, J = 6.7 Hz, 2H), 3.61 (t, 6.7 Hz, 2H), 8.42 (dd,J = 1 .3, 7.9 Hz, 1 H), 8.50-8.53 (m, 6H), 9.67-9.70 (m, 2H), 9.75-9.81 (m, 6H). HRMS (ESI- j m / z: calcd for CzsHiooNwNaaOsoSeSi-s: 893.2162 [M~2Na]2"; found: 893.2115.

[0358] Compound 70: Yield 81%.!H NMR (400 MHz, CD3OD): 6 -2.79 (s, 12H), -2.13 (t, J = 8.4 Hz, 4H), -1.00—0.92 (m, 4H), 1.67-1 .74 (m, 12H), 2.01 (t. J = 8.5 Hz, 4H). 2.48 (t, J = 2.6 Hz, 1 H), 2.75-2.78 (m, 24H), 3.02 (dt, J = 2.6, 7.2 Hz, 2H), 3.61 (t, J= 7.2 Hz, 2H), 8.44 (dd, J - 1 .3, 7.9 Hz, 1 H), 8.50-8.53 (m, 6H), 9.67 (s, 1 H), 9.70 (d, 7.9 Hz, 1 H), 9.77-9.82(m, 6H), HRMS (ESI") m / z: calcd for CfrjHsoNioNagOaoSeSis: 815.1494 [M-2Na]2-; found: 815.1451.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0359] Compound 71: Yield, 89%.1H NMR (400 MHz, CD3OD): 6 1 .34-1 .41 (m, 6H), 1.55-1.62 (m. 4H), 2.15 (t, J = 7.6 Hz, 2H), 3.27 (t, J - 6.9 Hz, 2H). HRMS (ESI+) m / z: calcd for CgHuNsNazOz: 230.0876 [M+Na]+; found: 230.0867.

[0360] Compound 73: Yield , 97%. ' H NMR (400 MHz, CD3OD): 0 1 .35-1 .42 (m, 6H) , 1.56-1.63 (m, 4H), 2.29 (t, J = 7.4 Hz, 2H), 3.28 (t, J= 6.9 Hz, 2H). HRMS (ESI") m / z: calcd for C8H14N3O2: 184.1092 [M-H]-; found: 184.1085.

[0361] p-TzEtdR700C8COOH: Yield, 75%.1H NMR (400 MHz, CD3OD): 6 -2.79 (s, 12H), -2.13 (t, J - 8 4 Hz, 4H), -1.00—0.92 (m, 4H), 1 .33-1 .41 (m, 6H), 1.59-1.63 (m, 2H), 1.68- 1.75 (m, 12H), 1.93-1.96 (m, 2H), 2.02 (t, J= 8.1 Hz, 4H), 2.18 (t, J= 7.6 Hz, 2H), 2.75-2.79 (m, 24H), 3.53 (t, J = 8.0 Hz, 2H), 3.77 (t, J - 8.0 Hz, 2H), 4.42 (t, J = 7.2 Hz, 2H), 8.02 (s, 1 H), 8.37 (dd, J ■= 1 .2, 7.9 Hz, 1 H), 8.51-8.53 (m, 6H), 9.64 (s, 1 H), 9.67 (d, J -■= 7.9 Hz, 1 H), 9.76-9.81 (m. 6H). HRMS (ESI”) m / z: calcd for CzpH^Nw^O^SsSi3: 918.6986 [M-2Na]z“; found: 918.6943.

[0362] p-TzEt-IR700C8SE: HRMS (ESI”) m / z: calcd for CyeHgsNi^NaaC^SeSh: 956.2158 [M-2Na]2-; found: 956.2110.Example 5

[0363] In this example, compounds comprising a styrene-like linker group were prepared using a Heck reaction with p-Br SiPc-NHa and styrene having a linker as detailed below and summarized in Scheme 38.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 38

[0364] Procedure for making Compound 75: Compound 74 (4-Vinylphenol, 2.39 g, 19.9 mmol), methyl 6-bromohexanoate (3.80 g, 18.2 mmol) and potassium carbonate (7.03 g, 50.8 mmol) were dissolved in acetone (15 mL), and the mixture was refluxed for 14 hours. After the addition of 1 M HCI and brine, the reaction mixture was extracted with CH2CI2. The organic layer was dried over NajSCH, filtered and evaporated. The residue was purified by4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 silica gel column chromatography (eluent: hexane / CHaCk, 5 / 1 to 0 / 1) to give 75 (3.76 g, 15.1 mmol, y. 76%) as a colorless oil.1H NMR (400 MHz, CDCI3): S 7.33 (d, 8.7 Hz, 2H), 6.84(d, J - 8.7 Hz, 2H), 6.65 (dd, J- 17.6, 10.9 Hz, 1 H), 5.60 (dd, 17.6, 0.9 Hz, 1 H), 5.11 (dd, J = 10.9, 0.9 Hz, 1 H), 3.96 (t, J = 6.4 Hz, 2H), 3.67 (s, 3H), 2.35 (t, J = 7.5, 2H), 1 .83- 1.76 (m, 2H), 1.74-1.66 (m, 2H), 1.54-1.48 (m, 2H). HRMS (ESH) m / z: calcd for CiSH2iO3: 249.1485 [M+H]4; found: 249.1484.

[0365] Procedure for making Compound 76: p-Br-SIPc-NH2(331 mg) and bis(tri- tert- buthylphosphine)palladium (Pd[P( / Bu)3h) (12.0 mg, 67 pmol) were dissolved in toluene (12 mL). and the mixture was stirred at room temperature under an Ar atmosphere. N- methyldicyclohexyiamine (CyaNMe) (175 mg, 896 pmol) and compound 75 (365 mg, 1.47 mmol) were added, and the mixture was stirred at 100 °C for 24 hours. The crude product was extracted with CH2CI2. The organic layer was dried over Na2SOa, filtered and evaporated to afford 76 (585 mg), which was used in the next step without further purification.

[0366] Procedure for making Compound 77: Compound 76 (368 mg), 1 ,3-propanesultone (2.21 g, 18.1 mmol), and A / ,A / -diisopropylethylamine (3.17 g, 24.5 mmol) were dissolved in MeOH (18 mL), and the mixture was stirred at 50 °C for 48 hours under an Ar atmosphere. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent B (CH3CN) (A / B = 70 / 30 to 0 / 100 in 50 min. The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the product (17.1 mg, 9.1 pmol, y. 0.5% in 4 steps as a sodium salt).NMR (400 MHz, CD3OD): 89.90-9.88 (m, 2H), 9.80-9.78 (m, 6H), 9.73 (d, J= 8.1 Hz, 1 H), 8.73 (d, J = 8.1 Hz, 1 H), 8.55-8.52 (m, 7H), 7.89 (d, J= 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 4.12 (t, J = 6.3 Hz, 2H), 3.71 (s, 3H), 2.82-2.77 (m, 24H), 2.44 (t, J = 7 A, 2H), 2.07-2.03 (m, 4H), 1.93- 1.86 (m, 2H), 1.79-1.72 (m, 14H), 1.64-1.58 (m, 2H), -0.85—0.93 (m, 4H), -2.08— 2.12 (m, 4H), -2.74 (s, 12H). HRMS (ESh) m / z: calcd for C7;,H94Nic.Na2O23S6Si3: 912.1966 [M-2Na]2~; found: 912.1927.

[0367] Procedure for making Styrl-IR700 C6COOH: Compound 77 (12.6 mg, 6.7 pmol) was dissolved in CH3CN containing 20 vol% of H2O (1 mL). Triethylamine (75.0 mg, 741 pmol) was added followed by the lithium bromide (183 mg, 2.11 mmol). The mixture was stirred vigorously at room temperature for 24 hours. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent B (CH3CN) (A / B = 70 / 30 to 50 / 50 in 50 min, 50 / 50 to 0 / 100 in 5 min. The product was desalted with a Sep-Pak CI S cartridge and cation-exchange resin, affording the product (8.34239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 mg, 4.4 pmoL y. 66% as a sodium salt). NMR (400 MHz, CDsOD): 89.89-9.87 (m, 2H), 9.81-9.79 (m. 6H), 9.73 (d, J= 8.2 Hz, 1 H), 8.74 (d, J= 8.2 Hz, 1 H), 8.57-8.52 (m, 7H), 7.88 (d, J = 7.1 Hz, 2H), 7.08 (d, J = 7.1 Hz, 2H), 4.12 (t, J= 6.5 Hz, 2H), 2.81-2.78 (m, 24H), 2.27 (t, J = 7.5, 2H), 2.06-2.04 (m, 4H), 1.93-1.87 (m, 2H), 1.76-1.71 (m, 14H), 1.64-1.57 (m, 2H), -0.92—0.94 (m, 4H), -2.06— 2.10 (m, 4H), -2.74 (s, 12H). HRMS (ESI”) m / z: calcd for C74H9iNi0Na3O23SsSi3: 916.1792 [M-2Na]2~: found: 916.1760.

[0368] Procedure for making Styrl-IR700 C6SE: Styrl-I R700 C6COOH (3.8 mg, 2.0 pmol), A / ,A / -disuccinimidyl carbonate (17.2 mg, 67 pmol) and triethylamine (32.0 mg, 316 pmol) were dissolved in dry dimethyl sulfoxide (770 pL) at room temperature under Ar atmosphere, and the mixture was stirred at room temperature for 26 hours. After addition of EtzO (40 mL) to the reaction mixture, precipitation occurred. The precipitates were collected and washed by Et?O (40 mL) to afford Styrl-IR700 C6SE (9.5 mg), which was used in the conjugation reaction to Cetuximab without further purification. HRMS (ESI") m / z: calcd for CzsHssNnNasOasSoSis: 953.6970 [M-2Na]2’; found: 953.6930.Example 6

[0369] In this example, a compound comprising a triazole-containing linker in combination with a PEG linker is described. The compound was made according to the method described in detail below and summarized in Scheme 39.Scheme 394239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0370] Compounds 79, p-Tz-IR700PEG6COOH, and S-Tz-IR700PEG6SE were made according to the methods described in Exampie 2.

[0371] P-TZ-IH700PEG6COOH: Yield, 90%.1H NMR (400 MHz, CD3OD): 3 -2.76 (s. 6H), -2.76 (s, 6H), -2.15—2.11 (m, 4H), -0.94—0.88 (m, 4H), 1.67-1.75 (m, 12H), 2.02 (t, J = 8.4 Hz, 4H), 2.46 (t,6.5 Hz, 2H), 2.74-2.80 (m, 24H), 3.64-3.66 (m, 12H), 3.72-3.79 (m,8Hj, 3.83-3.85 (m, 2H), 4.19 (t, J == 5.1 Hz, 2H), 4.90 (t, <7 = 5.1 Hz, 2H), 8.51-8.55 (m, 6H), 9.06 (dd, 1.3, 8.0 Hz, 1 H), 9.27 (s, 1 H), 9.78-9.80 (m, 5H), 9.83-9.87 (m, 2H), 10.20 (s, 1 H). HRMS (ESI”) m / z: calcd for C-yH wNnNasOssSBSis: 1001 .7225 [M-2Na]2~; found: 1001.7182.

[0372] p-Tz-IR700PEG6SE: HRMS (ESI j m / z: calcd for CsiHweNuNazOsoSeSis: 1039.2397 [M-2Na]?-; found: 1039.2349.

[0373] Compound 79: Yield, 98%.!H NMR (400 MHz, CD3OD): 52.46 (t, J - 6.5 Hz, 2H), 3.40 (t, J = 4.8 Hz, 2H), 3.63-3.68 (m, 22H), 3.71 (t, J = 9.3 Hz, 2H). HRMS (ESI4) m / z: calcd for CisHasNsNaaOs: 424.1666 [M+Na]+; found: 424.1654.Example 7

[0374] In this example, a compound comprising the Linker group at the alpha position is made. The compound was made according to the method described in detail below and summarized in Scheme 40.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 40

[0375] Procedure for making Compound 83: Deoxygenated dimethylforamide (3 mL) was added to compound 82 (393 mg, 0.884 mmol), Zn(CN)z(257 mg, 2.19 mmol) and Pd(PPhs)4 (523 mg, 0.453 mmol) under an Ar atmosphere, and the mixture was stirred at 130CC for 6 hours. Then, 8% NFUOH was added to the reaction solution, which was extracted with CH2CI2. The organic layer was washed with H2O, dried over Na2SO4, filtered and evaporated. The residue was purified with silica gel column chromatography to afford the4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 pure product. (87 mg, 0.258 mmol, y. 29%).1H NMR (400 MHz, CDCh): 60.98-0.99 (m, 21 H), 2.71 (t, J - 6 8 Hz, 2H), 3.12 (t, J- 6.8 Hz, 2H), 7.63 (t, J - 7.7 Hz, 1 H), 7.68 (dd, 1.5, 7.7 Hz, 1 H), 7.72 (dd, J= 1.5, 7.7 Hz, 1 H). HRMS (ESI+) m / z: calcd for C2iH2SN2NaSi : 359.1914 [M+Na]+; found: 359.1903.

[0376] Compound 84 was made according to the method described in Example 1 . Compounds 85, 86, 87, 88, and a-TzEt-!R700C8COOH were made according to the method described in Example 2. Compounds 81 and 82 were made according to the method described in Example 4.

[0377] Compound 81.' Yield, 78%. ’H NMR (400 MHz, CDCh): 34.65 (s, 2H), 7.17 (t, J = 7.8 Hz, 1 H). 7.40 (dd, J - 1 .6, 7.8 Hz, 1 H), 7.59 (dd, J - 1 .6, 7.8 Hz, 1 H).

[0378] Compound 82: Yield, 16%. ’H NMR (400 MHz, acetone-de): 6 1.01-1.04 (m, 21 H), 2.67 (t, J - 7.1 Hz, 2H), 3.09 (t, J- 7.1 Hz, 2H), 7.26 (t, J - 7.8 Hz, 1 H), 7.43 (dd, J- 1.6, 7.8 Hz, 1 H), 7.61 (dd, J= 1.6, 7.8 Hz, 1 H).

[0379] Compound 84: Yield, 50%.!H NMR (400 MHz, CD3OD): 60.91-0.98 (s. 21 H), 2.73 (t, J= 6.7 Hz, 2H), 3.33 (t, J= 6.7 Hz, 2H), 7.47 (t, J = 7.4 Hz, 1 H), 7.51 (dd, J= 1.2, 7.4 Hz, 1 H), 7.68 (dd, J = 1 .2, 7.4 Hz, 1 H). HRMS (ESH) m / z: calcd for Cai HsaNsSi: 354.2360 [M+H]4; found: 354.2363.

[0380] Compound 87: Yield, 7.6% (4 steps).2.77 (s, 12H), -2.15 (t, J = 8.4 Hz, 4H), -0.90—0.82 (m, 4H), 1 .15-1 .17 (m, 21 H), 1.66-1.73 (m, 12H), 2.01 (t, J- 8.3 Hz, 4H), 2.72 (t, J- 6.7 Hz, 12H), 2.76-2.80 (m, 12H), 3.63 (t, J- 7.4 Hz, 2H), 4.75 (t, J - 7.4 Hz, 2H), 8.35 (d, J - 6.5 Hz, 1 H), 8.38-8.46 (m, 2H), 8.49-8.54 (m, 5H), 9.68-9.73 (m, 2H), 9.78—9.81 (m, 5H). HRMS (ESI-) m / z: calcd for CysHiooNwNasOzoSeSi^ 893.2162 [M-2Na]2-; found: 893.2113.

[0381] Compound 88: Yield, 95%.!H NMR (400 MHz, CD3OD): 5 -2.77 (s, 12H), -2.16 (t, J = 8.4 Hz, 4H), -0.89—0.81 (m, 4H), 1.66-1.74 (m, 12H), 2.02 (t, J - 8.2 Hz, 4H), 2.63 (t, J - 2.5 Hz, 1 H), 2.72 (t, J = 6.7 Hz, 12H), 2.76-2.81 (m, 12H), 3.46 (dt, J = 2.5, 7.6 Hz, 2H), 4.76 (t, J - 7.6 Hz, 2H), 8.34 (ci, J - 6.8 Hz, 1 H), 8.42 (t, J - 7.5 Hz, 1 H), 8.48-8.54 (m, 6H), 9.72 (dd, J = 0.8, 7.5 Hz, 1 H), 9.78-9.82 (m, 6H). HRMS (ESI-) m / z: calcd for C64H8oNioNa202oS6Si3: 815.1494 [M-2Na]2-; found: 815.1454.

[0382] a-TzEt-IR700C8COOH: Yield, 71%.1H NMR (400 MHz, CD3OD): 5 -2.76 (s, 12H), -2.15 (t, J - 8.4 Hz, 4H), -0.90—0.81 (m, 4H), 1 .40-1 .48 (m, 6H), 1.66-1.74 (m, 14H), 2.00-2.04 (m, 6H), 2.21 (t, J = 7.6 Hz, 2H), 2.72 (t, J = 6.8 Hz, 12H), 2.76-2.80 (m, 12H),4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20253.95 (t, J= 7.9 Hz, 2H), 4.52 (t, J= 7.2 Hz, 2H), 4.98 (t, J = 7.9 Hz, 2H), 8.07 (s, 1 H), 8.25 (d, J = 7.1 Hz, 1 H). 8.35-8.40 (m, 2H), 8.46-8.54 (m, 5H), 9.42 (d, J- 7.6 Hz, 1 H), 9.71 (dd, J = 0.6, 7.6 Hz, 1 H), 9.75-9.80 (m, 5H). HRMS (ESP) m / z: calcd for C72H94N • Na,O;.4S8S!3: 918.6986 [M-2Na]2~: found: 918.6946.

[0383] a-TzEt-IR700C8SE: HRMS (ESH) m / z: calcd for CysHssN uNaaCXiSeSis: 956.2158 [M-2Na]2~: found: 956.2113.Example 8

[0384] In this example, a compound comprising a p-alkyne linker group installed via a Sonogashira coupling was prepared using the method detailed below and summarized in Scheme 41 .4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 41

[0385] Procedure for making f5-alkyne-IR700C7COOH: A solution of Pd(OAc)2 (0.05 mg, 0.22 pmol) and Cui (0.05 mg, 0,26 pmol) in CH3CN (0.1 mL) were added to a solution of p-l- SiPc (3.4 mg, 1.9 pmol) and P^n-CeHaSOsNais (0.4 mg, 0.70 pmol) in H2O (1 mL). Then, NE13 (0.1 mL) and a solution of compound 92 (4.1 mg, 26 pmol) in CH3CN (0.1 mL) were4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 added to the mixture, which was stirred at room temperature in the dark for 12.5 hours. The crude product was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the pure product as a sodium salt (3.5 mg, 1 .9 pmol, y.96%). 'H NMR (400 MHz, CD3OD): 0 -2.78 (s, 12H), -2.18—2.13 (m, 4H), -0.93—0.85 (m, 4H), 1.40-1.50 (m, 4H), 1 .62-1 .75 (m, 16H), 2.02 (t, J= 8.2 Hz, 4H), 2.16 (t, J = 7.6 Hz, 2H), 2.74-2.80 (m. 26H), 3.01 (t, J == 7.4 Hz, 2H), 3.35 (t, J - 7.2 Hz, 2H), 8.44 (dd, J == 1 .0, 8.3 Hz, 1 H), 8.51-8.54 (m, 6H), 9.69-9.71 (m, 2H), 9.76-9.80 (m, 6H).

[0386] p-alkyne-IR700C7SE: HRMS (ESI") m / z: calcd for CyeHgeNisNaaOjsSeSia: 949.2024 [M-2Na]z~; found: 949.1977.

[0387] Procedure for making Compound 94: N, A / ’-Dicyclohexylcarbodiimide (0.421 g, 2.04 mmol) was added to the solution of compound 93 (0.201 g, 2.05 mmol) and N- hydraxysuccinimide (0.262 g. 2.15 mmol) in tetrahydrofuran (5 mL) at 0 °C, and the mixture was stirred at 0 °C under an Ar atmosphere for 1 hour. Then, the reaction solution was further stirred at room temperature for 1 hour. The precipitate was filtered and the filtrate was evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (0.336 g, 1 .72 mmol, y. 84%).NMR (400 MHz, CDCI3): 6 2.05 (t, J= 2.7 Hz, 1 H), 2.62 (dt, J = 2.7, 7.4 Hz, 2H), 2.84 (s, 4H), 2.88 (t, J = 7.4 Hz, 2H). HRMS (ESI1) m / z: calcd for C9H10NO4: 196.0604 [M+H]+; found: 196.0595.

[0388] Procedure for making Compound 92: A solution of 7-aminoheptanoic acid (68 mg, 0.47 mmol) and NEt3(101 mg, 1.00 mmol) in H2O (1 mL) was added to a solution of compound 94 (59 mg, 0.30 mmol) in CH3CN (1 .5 mL), and the mixture was stirred at room temperature for 12.5 hours. The CH3CN was evaporated and the residue was acidified to pH3 with 3 mol / L HCIaq. Then, the solution was extracted with AcOEt, and the organic layer was dried over Na3SO4, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (58 mg, 0.26 mmol, y. 86%).:H NMR (400 MHz, CD3OD): 5 1.35-1.38 (m, 4H), 1.48-1.57 (m, 6H), 1.59-1.64 (m, 6H), 2.26 (t, J = 2.6 Hz, 1 H), 2.29 (t, J = 7.4 Hz, 2H), 2.36 (dt, J= 1.2, 7.1 Hz, 2H), 2.44-2.48 (m, 2H), 3.15- 3.20 (m, 2H), 8.00 (br, 1 H). HRMS (ESI") m / z: calcd for CI?HI8NO3: 224.1292 [M-Hp; found: 224.1286.

[0389] Compounds 90, and p-l-SiPc were made according to the procedure described in Example 1 .4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0390] Compound 90: Yield, 99%.1H NMR (400 MHz, CD3OD): 67.64 (dd, J= 0.5, 7.9 Hz, 1 H), 8.01 (dd, J - 1 .4, 7.9 Hz, 1 H), 8.27 (dd, J = 0.5, 1 .4 Hz, 1 H). HRMS (ESI ) m / z: calcd for CSH7IN3: 271 .9679 [M+H]*; found: 271 .9631 .

[0391] fi-l-SiPc: Yield, 2.1% (4 steps).1H NMR (400 MHz, CD3OD): 0 -2.78 (s, 12H), -2.20 (t, J = 8.4 Hz, 4H), -0.83—0.75 (m, 4H), 1.67-1.74 (m, 12H), 2.03 (t, J = 8.2 Hz, 4H), 2.73 (t, J- 6.8 Hz, 12 H), 2.77-2.81 (m, 12H), 8.51-8.54 (m, 6H), 8.61 (dd, J - 1.4, 8.1 Hz, 1 H), 9.53 (d, J - 8.1 Hz, 1 H), 9.76-9.79 (m, 6H), 10.08 (d, J - 0.8 Hz, 1 H). HRMS (ESH) m / z: calcd for CsoHysINioNasOaoSeSis: 852.0821 [M-2Na]2~; found: 852.0782.Example 9

[0392] In this example, compounds with alkene-containing linkers were prepared. The compounds were made according to the method detailed below and summarized in Scheme 42.Scheme 424239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0393] Procedure for making Compound 101: p-Br-SIPc-NHa (412 mg) and bis(tri-tert- buthylphosphine)palladium (Pd[P(fBu)3]2) (18.5 mg, 35.2 pmol) were dissolved in dioxane (17 mL), and the mixture was stirred at room temperature under an Ar atmosphere. / V- methyldicyclohexylamine (CyaNMe) (592 mg, 3.04 mmol) and methyl 10-undecenoate (457 mg, 2.30 mmol) were added, and the mixture was stirred at 100 °C for 24 hours. The crude product was extracted with CH2CI2. The organic layer was dried over NazSCX filtered and evaporated to afford 1 (1039 mg), which was used in the next step without further purification.

[0394] Procedure for making Compound 102: Compound 101 (1000 mg), 1 ,3- propanesultone (2.90 g, 23.8 mmol), and / V. / V-diisopropylethylamine (5.18 g, 40.0 mmol) were dissolved in MeOH (15 mL), and the mixture was stirred at 70 °C for 3 hours under microwave irradiation. This operation was repeated 5 times. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent B (CH3CN) (A / B = 70 / 30 to 0 / 100 in 50 min. The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the product (7.5 mg, 4.1 pmol, y. 0.2% in 4 steps as a sodium salt). ’H NMR (400 MHz, CD3OD): 89.74-9.62 (m, 6H), 9.60-9.57 (m, 2H), 8.47-8.41 (m, 7H), 7.12 (d, J= 15.9 Hz, 1 H), 7.03-6.98 (m, 1 H), 3.58 (s, 3H), 2.71-2.65 (m, 24H), 2.50-2.44 (m, 2H), 2.28 (t, J = 7.4, 2H), 1.95-1.91 (m, 4H), 1.67-1.57 (m, 12H), 1.51-1.20 (m, 12H), -0.97— 0.99 (m, 4H), -2.21— 2.25 (m, 4H), -2.86 (s, 12H). LRMS (ESI") m / z: [M+2H~4Na]2~ calcd for CzaHgaNwOzaSsSis, 865; found, 866.

[0395] Procedure for making IR700-alkene-COOH: Compound 102 (5.8 mg, 3.1 pmoi) was dissolved in CH3CN containing 30 vol% of H2O (1.4 mL). Triethylamine (60.0 mg, 593 pmo!) was added followed by the lithium bromide (181 mg, 2.08 mmol). The mixture was stirred vigorously at room temperature for 24 hours. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent B (CH3CN) (A / B - 70 / 30 to 50 / 50 in 50 min, 50 / 50 to 0 / 100 in 5 min. The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the product (2.8 mg, 1.5 pmol, y. 48% as a sodium salt).!H NMR (400 MHz, CD3OD): 59.72-9.55 (m, 6H), 9.57-9.55 (m, 2H), 8.46-8.39 (m, 7H), 7.09 (d, J - 15.8 Hz, 1 H), 7.01-6.94 (m, 1 H), 2.69- 2.64 (m, 24H), 2.47-2.42 (m, 2H), 2.10 (t, J= 7.7, 2H), 1.93-1.89 (m, 4H), 1.67-1.61 (m, 12H), 1.49-1.34 (m, 8H), 1 .20-1.19 (m, 4H), -1.02—1.05 (m, 4H), -2.21—2.25 (m, 4H), -2.87 (s, 12H). LRMS (ESI") m / z: [M+3H-5Na]2” calcd for C7iH96Nio022S6Si3, 858; found, 859.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0396] Procedure for making IR700-alkene-SE: IR700-alkene-COOH (1 .0 mg, 0.5 pmol), A / ,A / -disuccinimidyl carbonate (3.3 mg, 13 pmol) and triethylamine (10.0 mg, 99 umol) were dissolved in dry dimethyl sulfoxide (500 pL) at room temperature under Ar atmosphere, and the mixture was stirred at room temperature for 21 hours. After addition of EtgO (40 mL) to the reaction mixture, precipitation occurred. The precipitates were collected and washed by EW (40 mL) to afford IR700-alk.ene-SE (9.2 mg), which was used in the conjugation reaction to Cetuximab without further purification. LRMS (ESP ) m / z: [M+2H~4Na]2' calcd for C75H99N11 C^SgSis, 907; found, 907.Example 10

[0397] In this example, compounds comprising alkoxy groups within the phthalocyanine core were prepared according to the method described below and summarized in Scheme 43.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0398] Compound 101: Compound 45 (0.331 g, 1 .02 mmol), 1 ,3-diiminoisoindoline (0.440 g, 3.03 mmol) and SiCLi (1 .02 g, 6.03 mmol) were dissolved in quinoline (3 mL) and the mixture was stirred at 210°C under an Ar atmosphere for 2 h. After cooling, MeOH was added to the mixture and the precipitate was collected, washed with MeOH and dried (0.490 g). The crude product was used for the next step without further purification.

[0399] Compound 102: Crude compound 101 (0.204 g) and 4-amino-1 -butanol (70 mg, 0.785 mmol) was dissolved in toluene (50 mL). NaH (20 mg, 0.829 mmol) was added to the solution, and the reaction mixture was stirred at 130°C under an Ar atmosphere for 7 h. After evaporation, the crude product was suspended with HsO / MeOH = 10 / 1 solution, washed and dried (0.168 g). The mixture of A4-type and A3B-type silicon phthalocyanines was used for the next step without further purification.

[0400] Compound 103: A mixture of Artype and A3B-type silicon phthalocyanines (162 mg), 1 ,3-propanesultone (1 .13 g, 9.23 mmol) and / PrsEtN (1 .52 g, 11 .8 mmol) were dissolved in MeOH (10 mL) and the mixture was stirred at 50°C under an Ar atmosphere for 20.5 h. The reaction solution was concentrated and the residue was purified with reversephase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). Repurification was performed. The product was desalted with a Sep-Pak Cl 8 cartridge and cation-exchange resin, affording compound 103. In HPLC purification, the intermediate reacted with five 1 ,3-propanesultone was also collected and subjected to the same reaction again to afford additional compound 103 (totally 5.3 mg, 3.08 pmol, 0.8% (3 steps)).1H NMR (400 MHz, CD3OD): 0 -1 .94— 1.88 (m, 4H), -1.46— -1.39 (m, 4H), ~0.91~-0.83 (m, 4H), 1.36-1.47 (m. 37H), 2.55 (t, J = 6.6 Hz, 12H), 2.58-2.63 (m, 12H), 8.50-8.55 (m. 7H), 9.73- 9.75 (m, 2H), 9.76-9.80 (m, 6H). HRMS (ESI") m / z: calcd for CesHssNioNasOsoSeSh: 835.1923 [M~2Na]2~: found: 835.1942.

[0401] Compound 104: Compound 104 was synthesized according to general procedure of deprotection reaction of triisopropylsilyl group. Yield 86%.1H NMR (400 MHz, CD3OD): 6 -1.92 (t, J - 5.8 Hz, 4H), -1.45—1.38 (m, 4H), -0.94—0.87 (m, 4H), 1.35-1.47 (m, 16H), 2.56 (t, J = 6.6 Hz, 12H), 2.58-2.63 (m, 12H), 4.08 (s, 1 H), 8.51-8.55 (m, 7H), 9.74 (dd, J = 0.7, 7.9 Hz, 1 H), 9.76-9.81 (m, 7H). HRMS (ESI") m / z: calcd for CsoHesNioNasO^SeSi: 757.1256 [M-2Na]?"; found: 757.1265.

[0402] $-Tz4R700CWCOOH-a!k: p-Tz-IR700C10COOH-a!k was synthesized according to general procedure of click reaction. Yield 90%.NMR (400 MHz, CD3OD): 5 -1 .89 (t, J = 5.7 Hz, 4H), -1.41—1.35 (m, 4H), -0.98—0.91 (m, 4H), 1.36-1.48 (m, 22H), 1.52-1.58 (m, 4H), 1.61-1.69 (m, 2H), 2.19 (t, J= 7.6 Hz, 4H), 2.55-2.63 (m, 24H). 4.67 (t, J = 7.4 Hz, 2H),4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20258.52-3.55 (m, 6H), 9.02 (dd, J = 1.4, 8.0 Hz, 1 H), 9,15 (s, 1 H), 9.78-9.86 (m, 5H), 9.82-9.86 (m. 2H), 10.2 (dd, J = 0.8, 1 .4 Hz, 1 H). HRMS ( ESi ) m / z: caicd for C7.3H86Ni3Na3O22S6Si: 874.6904 [M-2Nap-: found: 874.6927.

[0403] @-Tz-IR700C1 OSE-alk: p-Tz-IR700C10SE-alk was synthesized according to general procedure of synthesis of succinimidyl ester compounds.Example 11

[0404] In this example, compounds comprising a naphthylene ring system within the phthalocyanme core were prepared according to the method described below and as summarized in Scheme 44.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 44

[0405] Compound 106: Compound 105 (0.513 g, 2.00 mmol), (triisopropylsilyl)acetylene (0.726 g, 3.98 mmol), PdCI2(PPh3)2(15.7 mg, 22.4 pmol) and Cui (4.4 mg, 23.1 prnol) were dissolved In tetrahydrofuran (10 mL) under an Ar atmosphere. Then, / Pr2EtN (0.521 g, 4.03 mmol) were added to the solution and the mixture was stirred at 80°C for 8.5 h. After that, saturated NHnClaq was added to the reaction mixture, which was extracted with AcOEt. The organic layer was washed with saturated NaClaq, dried over Na2SO4, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the pure product (0.307 g, 0.856 mmol, y. 43%).1H NMR (400 MHz, CDCh): 5 1.16-1.18 (m, 21 H), 7.80 (dd, J = 1 .5, 8.6 Hz, 1 H), 7.91 (d , J = 8.6 Hz, 1 H), 8.07 (d, J = 0.6 Hz, 1 H), 8.28 (s, 1 H), 8.31 (s, 1 H). HRMS (ESI4) m / z: calcd for C23H26N2NaSi: 381 .1758 [M+Na]+; found: 381 .1747.

[0406] Compound 107: Compound 107 was synthesized according to general procedure of synthesis of substituted 1 ,3-diiminoisoindoline derivatives. Yield 99%.1H NMR (400 MHz, CD3OD): 6 1.19 (s, 21 H), 7.65 (dd, 1.6, 8.6 Hz, 1 H), 8.04 (d, J = 8.6 Hz. 1 H), 8.17 (d, J = 0.7 Hz, 1 H). 8.30 (s, 1 H), 8.31 (s, 1 H). HRMS (ESH) m / z: calcd for CzsHsoNsSi: 376.2204 [M+Hp; found: 376.2198.

[0407] Compound 108: Compound 108 was synthesized according to general procedure of synthesis of AsB-type silicon phthalocyanine dihydroxide derivatives (compound 46, 67, 85).

[0408] Compound 109: Compound 109 was synthesized according to general procedure of addition reaction of axial ligands to A3B-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86).

[0409] Compound 110: Compound 110 was synthesized according to general procedure of alkyl sulfonation of AsB-type silicon phthalocyanine derivatives (compound 48, 69, 87). Yield 3.8% (4 steps).1H NMR (400 MHz, CD3OD): 6 -2.67 (s, 12H), -2.03 (t, J = 8.3 Hz, 4H), -0.91—0.82 (m, 4H), 1.30 (s, 21 H), 1.66-1.74 (m, 12H), 2.04 (t, J = 8.3 Hz, 4H), 2.73-2.79 (m, 24H), 8.00 (dd, J = 1 .4, 8.5 Hz, 1 H), 8.47-8.53 (m, 6H), 8.85 (d,8.5 Hz, 1 H), 8.99 (s,1 H), 9.73-9.76 (m, 4H), 9.79-9.83 (m, 2H), 10.3 (t, J= 2.7 Hz, 2H). HRMS (ESI") m / z: calcd far C / sHgaNioNasOaoSgSiT 904.2083 [M-2Na]2"; found: 904.2112.

[0410] Compound 111: Compound 110 was synthesized according to general procedure of deprotection reaction of triisopropylsilyl group. Yield 89%.1H NMR (400 MHz, CDgOD): 6 -2.68 (s, 12H), -2.02 (t, J = 8.4 Hz, 4H), -0.93—0.84 (m, 4H), 1.66-1.74 (m, 12H), 2.04 (t, J - 8.2 Hz, 4H), 2.73-2.77 (m, 24H), 3.90 (s, 1 H), 8.02 (dd, J - 1.5, 8.5 Hz, 1 H), 8.49 (dd, J = 2.8, 5.7 Hz, 2H), 8.52 (dd, J - 2.8, 5.7 Hz, 4H), 8.86 (d, J - 8.7 Hz, 1 H), 9.04 (s, 1 H), 9.73- 9.76 (m, 4H), 9.81-9.84 (m, 2H), 10.3 (s, 2H). HRMS (ESH) m / z: calcd for CseH / BNic.NaoOsoSeSis: 826.1416 [M-2Na]2’; found: 826.1442.

[0411] p-Tz-naph-IR700C10COOH: p-Tz-naph-IR700C1 OCOOH was synthesized according to general procedure of click reaction. Yield 85%.1H NMR (400 MHz, CD3OD): 5 -2.66 (s, 12H), -2.01 (t, J= 8.4 Hz, 4H), -0.92—0.83 (m, 4H), 1.37-1.42 (m, 6H), 1.48-1.52 (m, 4H), 1.62-1.74 (rn, 14H), 2.05 (t, 8.2 Hz, 4H), 2.09-2.15 (m, 2H), 2.20 (t, J- 7.5 Hz,2H), 2.74-2.78 (m, 24H), 4.61 (t, J= 7.3 Hz, 2H), 8.48 (dd, J= 2.9, 5.8 Hz, 2H), 8.51-8.534239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025(m, 4H), 8.58 (dd, J = 1.5, 8.6 Hz, 2H), 8.87 (s, 1 H), 8.97 (d, J= 8.9 Hz, 1 H), 9.31 (s, 1 H), 9.73-9.76 (m, 4H), 9.81-9.84 (m, 2H), 10.3 (s, 1 H), 10.4 (s, 1 H). HRMS (ESI ) m / z: calcd for CyeHggNisNasC^SeSia: 943.7065 [M-2Na]2~; found: 943.7097.

[0412] @-Tz-naph-IR700Cl0SE: |3-Tz-naph-IR700Cl OSE was synthesized according to genera! procedure of synthesis of succinimidyl ester compounds. HRMS (ESI-) m / z: calcd for CsoHiooNiaNasOa-iSoSig: 981 .2237 [M-2Na]2~; found: 981 .2271 .Example 12

[0413] In this example, compounds comprising chloro or iodo substituents attached to the phthalocyanine core in addition to a Linker-X group were prepared according to the method described below and summarized in Scheme 45.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 45

[0414] Compound 1 13: Compound 1 12 (6.00 g, 40.8 mmol) and h (10.4 g, 41.1 mmol) were dissolved in fuming H2SO4 (30%, 20 mL) and the reaction mixture was stirred at 100°C4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 for 41 h. The mixture was poured into ice and the precipitate was collected, washed with 2% K2CO3aq and saturated NaNO2aq, and dried. The crude product was purified with silica gel column chromatography (7.13 g). In some examples, the product still contained unknown impurities, but was used for the next step without further purification. In other examples, the compound was purified and the following characterization data were obtained: HRMS (ESI ) m / z: calcd for C8H2I2NO2: 397.8180 [M-H]-; found: 397.8197.

[0415] Compound 114: Compound 113 (4,90 g) was suspended in NH4OH (60 mL) and the mixture was stirred at 60°C for 1 .5 h. Then, the precipitate was collected, wash with cold H2O and MeOH, and dried to afford the product (3.21 g, 7.71 mmol, 27% (2 steps)). 'H NMR (400 MHz, DMSO-de): 6 7.43 (br, 2H), 7.84 (br, 2H), 7.92 (s, 2H). HRMS (ESI-) m / z: calcd for C8H6l2N2NaO2: 438.8411 [M+Na]+; found: 438.8394.

[0416] Compound 115: Compound 114 (1 .01 g, 2.43 mmol) was dissolved in pyridine (35 mL) and dioxane (15 mL) under an Ar atmosphere and POCI3 (2.2 mL, 23.5 mmol) was slowly added dropwise to the solution at 0°C. Then, the reaction mixture was stirred at room temperature for 11 h. H2O was added to the mixture at 0cC, followed by extraction with AcOEt. The organic layer was washed with H2O and saturated NaClaq, dried over Na2SO4, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (0.694 g, 1 .83 mmol, 75%).1H NMR (400 MHz., CDCh): 5 8.22 (s, 2H). HRMS (ESI") m / z\ calcd for C3HI2N2: 378.8235 [M-H]-; found: 378.8241 .

[0417] Compound 116, 117: Compound 115 (0.703 g, 1 .85 mmol), (triisopropylsilyl)acetylene (0.511 g, 2.80 mmol), Pd(PPh3)4(0.104 g, 90.0 pmol), Cui (34.2 mg, 180 pmol) and NEt3(0.579 g, 5.72 mmol) were dissolved in tetrahydrofuran (12 mL) and the mixture was stirred at 60°C under an Ar atmosphere for 18 h. Then, saturated NH4Claq was added to the mixture, followed by extraction with AcOEt. The organic layer was washed with saturated NaClaq, dried over Na2SO4, filtered and evaporated. The crude product was purified with silica gel column chromatography. For complete separation of compound 116 and compound 117, additional column chromatography was performed two times to afford pure compound 116 (87.5 mg, 0.201 mmol, 11%) and compound 117 (91 .2 mg, 0.187 mmol,1.19 (m, 21 H), 7.77 (d, J = 0.3 Hz, 1 H), 8.26 (d, J = 0.3 Hz, 1 H) for compound 116.1H NMR (400 MHz, CDCIs): 6 1.12-1.15 (m, 42H), 7.83 (s, 2H) for compound 117. HRMS (ESI-) m / z: calcd for CigH23lN2NaSi: 457.0567 [M+H] \ found: 457.0555 for compound 116. HRMS ( ESI+) m / z: calcd for C3oH44N2NaSI2: 511 .2935 [M+Na]+; found: 511 .2922 for compound 1 17.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0418] Compound 118: Compound 118 was synthesized according to general procedure of synthesis of substituted 1 ,3-diiminoisoindoline derivatives. Yield 96%.1H NMR (400 MHz, CD3OD): 5 1.21 (s, 21 H), 8.00 (d, J = 0.5 Hz, 1 H), 8.41 (d, J = 0.5 Hz, 1 H). HRMS (ESI4) m / z: calcd for C19H27IN3S1: 452.1014 [M+H]+; found: 452.1003.

[0419] Compound 119, 120: Compound 119 was synthesized according to general procedure of synthesis of A3B-type silicon phthalocyanine dihydroxide derivatives (compound 46, 67, 85) except for chemical equivalent of SiCk (2.8 eq). Compound 120 was obtained as a reaction byproduct. The mixture was used as is for the next step.

[0420] Compound 121, 122: Compound 121 and compound 122 were synthesized according to general procedure of addition reaction of axial ligands to A3B-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86). The mixture was used as is for the next step.

[0421] Compound 123, 124: Compound 123 and compound 124 were synthesized according to general procedure of alkyl sulfonation of A3B-type silicon phthalocyanine derivatives (compound 48, 69, 87) except for chemical equivalent of 1 ,3-propanesultone (40 eq). In some examples, reverse-phase HPLC was performed, but compound 123 and compound 124 could not be separated. The mixture was used as is for the next step. In other examples, the compounds could be separated and the following characterization data were obtained: HRMS (ESI*) m / z: calcd for CziHssINioNaaOsoSsSk: 942.1488 [M-2Na]2-; found: 942.1517 for compound 123. HRMS (ESI j m / z: calcd for CTiHosCINioNazOzoSeSi*: 896.1810 [M-2Na]2“; found: 896.1838 for compound 124.

[0422] Compound 125, 126: Compound 125 and compound 126 were synthesized according to general procedure of deprotection reaction of triisopropylsilyl group. Yield 2.7% (5 steps) for compound 126. Compound 125 still contained unknown impurities after reversephase HPLC purification.4H NMR (400 MHz, CD3OD): 5 --2.76 (s, 12H), -2.20 (t,8.4 Hz,4H), -0.78—0.70 (m, 4H), 1.66-1.74 (m, 12H), 2.03 (t, J - 8.2 Hz, 4H), 2.72 (t, J - 6.7 Hz, 12H), 2.78-2.82 (m, 12H), 4.42 (s, 1 H), 8.50-8.55 (m, 6H), 9.75-9.80 (m, 7H), 9.87 (s, 1 H). HRMS (ESI j m / z: calcd for Ce.2H75IN10Na2O2eSe.Si3: 864.0821 [M-2Na]2'; found: 864.0850 for compound 125. HRMS (ESI+) m / z: calcd for Ce^HysCINioNajOaoSeSis: 818.1143 [M-2Na]2~; found: 818.1171 for compound 126.

[0423] @4-Tz-IR700C1 OCOOH: |3-l-Tz-IR700C1 OCOOH was synthesized according to genera! procedure of click reaction except for chemical equivalent of azido compound (1 eq). Yield 1 .0% (6 steps).1H NMR (400 MHz, CD3OD): 6 -2.75 (s, 12H), -2.18 (t, J = 8.4 Hz,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254H), -0.80—0.72 (m, 4H), 1.39-1.46 (m, 6H), 1.50-1.57 (m, 4H), 1.64-1.75 (m, 14H), 2.04 (t, J- 8.1 Hz, 4H), 2.16-2.22 (m, 4H), 2.72 (t, J - 6.7 Hz, 12H), 2.78-2.83 (m, 12H), 4.70 (t, J = 7.2 Hz, 2H), 8.50-8.55 (m, 6H), 8.91 (s, 1 H), 9.72-9.74 (m, 1 H), 9.77-9.81 (m, 5H), 9.88 (d, J = 0.4 Hz, 1 H), 10.3 (d, J = 0.4 Hz, 1 H). HRMS (ESI-) m / z: calcd for C72H93lNi3Na3O22S6Si3: 981.6469 [M~2Na]?"; found: 981.6506.

[0424] [3-CI-Tz-SR / OOCWCOOH: [3-CI-TZ-IR700C1 OCOOH was synthesized according to general procedure of click reaction. Yield 95%.NMR (400 MHz, CDsOD): 6 -2.75 (s, 12H), -2.18 (t, J= 8.4 Hz, 4H), -0.80—0.71 (m, 4H), 1.39-1.45 (m, 6H), 1.50-1.58 (m, 4H), 1.64-1.74 (m, 14H), 2.04 (t, J = 8.1 Hz, 4H), 2.15-2.22 (m, 4H), 2.71 (t, J = 6.7 Hz, 12H), 2.78-2.83 (m, 12H), 4.69 (t, J = 7.4 Hz, 2H), 8.51-8.55 (m, 6H), 9.01 (s, 1 H), 9.75-9.81 (m, 6H), 9.87 (s, 1 H), 10.3 (s, 1 H). HRMS (ESI j m / z: calcd for C72H93CIN:3Na3O22S6Si3: 935.6791 [M-2Na]2~; found: 935.6828.

[0425] @-I-TZ-IR700C10SE: p-l-Tz-IR700C10SE was synthesized according to general procedure of synthesis of succinimidyl ester compounds. HRMS (ESI ~) m / z: calcd for C76HS7lN14Na2O24S6Si3: 1019.1642 [M-2Na]2-; found: 1019.1684.

[0426] ^CI-Tz-!R7700CWSE: p-CI-Tz-IR700C10SE was synthesized according to general procedure of synthesis of succinimidyl ester compounds. HRMS (ESI j m / z: calcd for C78H97CINuNa2O24S6Si3: 973.1964 [M-2Na]% found: 973.2006.Example 13

[0427] In this example, compounds comprising a bromo substituent attached to the phthalocyanine core in addition to a Linker-X group were prepared according to the method described below and summarized in Scheme 46.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 46

[0428] Compound 128: Compound 127 (5.13 g, 22.7 mmol) and Is (5.75 g, 22.7 mmol) were dissolved in fuming H2SO4 (10 mL) and the mixture was stirred at 90°C for 45 h. Then,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 the reaction mixture was poured into ice and the precipitate was collected, washed with 2% KsCOsaq, saturated NaNO2aq and H2O, and dried (10.2 g). In some examples, the product contained unknown impurities, but was used for the next step. In other examples, the following characterization data were obtained: HRMS (ESI”) m / z: calcd for C8H2BrlNO2: 349.8319 [M-H]-; found: 349.8325.

[0429] Compound 129: Compound 128 (10.2 g) was suspended in NHjOH (80 mL) and the mixture was stirred at 60°C for 1 .5 h. Then, the precipitate was collected, wash with cold HaO and MeQH, and dried to afford the product (5.40 g, 14.6 mmol, 65% (2 steps)). ’H NMR (400 MHz, DMSO-do): 6 7.45 (br, 2H), 7.75 (s, 1 H), 7.85 (br, 2H), 7.96 (s, 1 H). HRMS (ESI+) m / z: calcd for C8H6BrlN2NaO2: 390.8550 [M~-Na]+: found: 390.8547.

[0430] Compound 130: Compound 129 (5.16 g, 14.0 mmol) was dissolved in pyridine (100 mL) and dioxane (40 mL) under an Ar atmosphere and POCIs (5 mL, 53.5 mmol) was slowly added dropwise to the solution at 0°C. Then, the reaction mixture was stirred at room temperature for 5 h. H2O was added to the mixture at 0°C. After evaporation, the residue was dissolved in AcOEt and the organic layer was washed with H2O and saturated NaClaq, dried over Na2SO4, filtered and evaporated. The crude product was purified with silica gel column NMR (400 MHz, N2: 330.8373

[0431] Compound 131 : Compound 130 (1.09 g, 3.29 mmol), (triisopropylsilyl)acetylene (0.824 g, 4.52 mmol), PdCl2(PPhs)2 (41 .7 mg, 59.4 pmol), Cui (60.6 mg, 318 pmol) and NEt8(0.625 g, 6.18 mmol) were dissolved in tetrahydrofuran (15 mL) and the mixture was stirred under an Ar atmosphere at room temperature for 12 h and at 60°C for 6.5 h. Then, saturated NHADIaq was added to the mixture, followed by extraction with AcOEt. The organic layer was washed with saturated NaClaq, dried over Na2SO4, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (0.821 g, 2.12 mmol, 64%).!H NMR (400 MHz, CDCI3): 6 1 .14-1 .16 (m, 21 H), 7.85 (d, 3 = 0.3 Hz, 1 H), 8.02 (d, 3- 0.3 Hz, 1 H). HRMS (ESI*) m / z: calcd for Ci9H23BrN2NaSi: 409.0706 [M+Na]+; found: 409.0694.

[0432] Compound 132: Compound 132 was synthesized according to general procedure of synthesis of substituted 1 ,3-diiminoisoindoline derivatives. Yield 99%. ’ H NMR (400 MHz, CD3OD): 6 1.19 (s, 21 H). 8.04 (d, 3 = 0.3 Hz, 1 H), 8.16 (d, 3 - 0.3 Hz, 1 H). HRMS (ESI+) m / z: calcd for CigHgyBrNaSi: 404.1152 [M+H]+; found: 404.1145.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0433] Compound 133; Compound 133 was synthesized according to general procedure of synthesis of A3B-type silicon phthalocyanine dihydroxide derivatives (compound 46, 67, 85) except for chemical equivalent of SiCL (2.6 eq).

[0434] Compound 734; Compound 134 was synthesized according to general procedure of addition reaction of axial ligands to A3B-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86).

[0435] Compound 735; Compound 135 was synthesized according to general procedure of alkyl sulfonation of A3B-type silicon phthalocyanine derivatives (compound 48, 69, 87). Compound 125 still contained unknown impurities after reverse-phase HPLC purification. In some examples, the following characterization data were obtained: HRMS (ESI j m / z: calcd for C71H95BrNioNa?02oS6Si4: 918.1558 [M-2Na]2-; found: 918.1597.

[0436] Compound 736; Compound 136 was synthesized according to general procedure of deprotection reaction of triisopropylsilyl group. Yield 0.4% (5 steps).1H NMR (400 MHz, CDsOD): 3 -2.76 (s, 12H), -2.21 (t, J = 8.4 Hz, 4H), -0.75—0.67 (m, 4H), 1 .66 -1.74 (m, 12H), 2.04 (t, J = 8.2 Hz, 4H), 2.71 (t, 3= 6.7 Hz, 12H), 2.78-2.82 (m, 12H), 4.41 (s, 1 H), 8.51-8.55 (m, 6H), 9.75-9.80 (m, 6H), 9.85 (s, 1 H), 9.97 (d, 3 = 0.4 Hz, 1 H). HRMS (ESI-) m / z: calcd for CezH-zsBrNioNasOsoSeSis: 840.0890 [M-2Na]2-; found: 840.0922.

[0437] p-Br~Tz~IR700C1 OCOOH: p~Br-Tz-IR700C1 OCOOH was synthesized according to general procedure of click reaction. Yield 67%. ^H NMR (400 MHz, CD3OD): 6 -2.75 (s, 12H), -2.18 (t, 3= 8.4 Hz, 4H), -0.79--0.72 (m, 4H), 1.40-1.46 (m, 6H), 1.50-1.58 (m, 4H), 1.67-1.74 (m, 14H), 2.04 (t, 3 = 8.1 Hz, 4H), 2.17-2.22 (m, 4H), 2.71 (t, 3 = 6.7 Hz, 12H), 2.79-2.83 (m, 12H), 4.69 (t, J = 7.3 Hz, 2H), 8.50-8.55 (m, 6H), 9.00 (s, 1 H), 9.73-9.76 (m, 1 H), 9.77-9.81 (m, 5H), 10.1 (d, 3= 0.3 Hz, 1 H), 10.1 (s, 1 H). HRMS (ESI j m / z: calcd for C / ?H.y;B:N-3Na;Oz?S;,S!:5: 957.6539 [M-2Na]2-; found: 957.6579.

[0438] p-Br-Tz-!R700C10SE: p-Br-Tz-IR700C10SE was synthesized according to general procedure of synthesis of succinimidyl ester compounds. HRMS (ESI-) m / z: calcd for CyeHsyBrNuNasOgiSsSis: 995.1711 [M-2Na]% found: 995.1746.Example 14

[0439] In this example, compounds comprising two linker groups and two X groups were prepared according to the method described below and summarized in Scheme 47.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 47

[0440] Compound 137: Compound 137 was synthesized according to general procedure of synthesis of substituted 1 ,3-diiminoisoindohne derivatives. Yield 99%.1H NMR (400 MHz, CD3OD): 5 1.18 (S, 42H), 8.04 (s, 2H). HRMS (ESH) m / z: calcd for CsoHpvNsNaSis: 528.3201 [M+Na]‘; found: 528.3189.

[0441] Compound 138: Compound 138 was synthesized according to general procedure of synthesis of AsB-type silicon phthalocyanine dihydroxide derivatives (compound 46, 67, 85).

[0442] Compound 139.' Compound 139 was synthesized according to general procedure of addition reaction of axial ligands to AsB-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0443] Compound 140; A crude compound 139 (0.217 g), 1 ,3-propanesultone (1 .1 1 g, 9.05 mmol) and / PrgEtN (1 .45 g, 1 1 .2 mmol) were dissolved in MeOH (10 mL) and the mixture was stirred at 50°C under an Ar atmosphere for 24 h. Then, AgF (224 mg, 1 .76 mmol) was added to the reaction mixture and the mixture was stirred at room temperature under an Ar atmosphere in the dark for 3.5 h. Saturated NH4Claq (1 mL) was added to the mixture and the mixture was stirred at room temperature in the dark far 10 min. The reaction solution was concentrated and the residue was purified with reverse-phase HPLC (eluent A: 0.1 M triethylamine acetate solution, eluent B: CH3CN). The product was desalted with a Sep-Pak Cl 8 cartridge and cation-exchange resin, affording the pure product as a sodium salt (5.3 mg, 3.17 pmol, 1.4% (5 steps)). ' H NMR (400 MHz, CD3OD): 6 -2.76 (s, 12H), -2.21 it, J- 8.4 Hz, 4H), -0.76—0.67 (m, 4H), 1.66-1.73 (m, 12H), 2.03 (t, J= 8.2 Hz, 4H), 2.71 (t, J = 6.7 Hz, 12H), 2.78-2.82 (m, 12H), 3.35 (s, 2H), 8.48 (dd, J = 2.9, 5.8 Hz, 1 H), 8.51-8.55 (m, 5H), 9.75-9.80 (m, 6H), 9.82 (s, 2H). HRMS (ESI") m / >: calcd for CwHysNioNaaOsoSsSis: 813.1338 [M~2Na]2~: found: 813.1367.

[0444] p-diTzdR700CWCOOH: p-diTz-IR700C10COOH was synthesized according to general procedure of click reaction. Yield 51%. ’ H NMR (400 MHz, CD3OD): 6 -2.74 (s, 12H), -2.13 (t, J = 8.3 Hz, 4H), -0.89—0.81 (m, 4H), 1.40-1.46 (m, 12H), 1 .49-1.54 (m, 8H), 1.64—1 .75 (m, 16H), 2.03 (t, J = 8.1 Hz, 4H), 2.07-2.14 (m, 4H), 2.21 (t, J = 7.6 Hz, 4H), 2.74 (t, J - 6.7 Hz, 12H). 2.78-2.82 (m, 12H), 4.60 (t, J = 7.3 Hz, 4H), 8.32 (s, 2H), 8.51- 8.55 (m, 6H). 9.77-9.82 (m, 6H), 10.0 (s, 2H). HRMS (ESI") m / z: calcd for CB4H1 | 2Ni6Na4O24S6Si3: 1048.2635 [M-2Na]2"; found: 1048.2675.

[0445] &-diTz-IR700C10SE: p-diTz-IR700C10SE was synthesized according to general procedure of synthesis of succinimidyl ester compounds. HRMS (ESI") m / z: calcd forCgsHijoNisNajOjgSsSis: 1 123.2979 [M-2Na]2"; round: 1123.3022.Example 15

[0446] In this example, compounds comprising ethyl-substituted silyl groups within the phthalocyanine core were prepared according to the method described below and summarized in Scheme 48.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 48

[0447] Compound 142: Compound 141 (2.01 g, 8.26 mmol) was dissolved in tetrahydrofuran (30 mL) under an Ar atmosphere. EtMgBr (3 M in EtsO, 6.9 mL, 20.7 mmol) was added to the solution and the mixture was stirred at 60°C for 3 h. AcOEt was added to the reaction mixture and the organic layer was washed with H2O and saturated NaClaq, dried over NazSCU, filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (1 .25 g, 5.23 mmol, 63%).1H NMR (400 MHz, CDCIs): 5 0.60-0.66 (m, 4H), 0.71-0.76 (m, 2H), 0.97 (t, J= 7.9 Hz, 6H). 1.87-1.954239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025(m, 2H), 3.41 (t, J = 7.0 Hz, 2H), 3.47 (s, 3H). HRMS (ESP) m / z: calcd for CsHi9BrNaOSi: 261.0281 [M+Na]‘; found: 261.0272.

[0448] Compound 143: Compound 143 was synthesized according io general procedure of synthesis of azido fatty acid compounds (compound 57, 59, 73). Yield 92%,1H NMR (400MHz, CDCI3): 5 0.60-0.68 (m, 6H), 0.98 (t, 4 = 7.9 Hz, 6H), 1.62-1.70 (m, 2H), 3.26 (t, 4 =7.0 Hz, 2H), 3.47 (s, 3H). HRMS (ESP) m / z: calcd for C8H19N3NaOSi: 224.1195 [M+Na]+: found: 224.1181.

[0449] Compound 144 / Compound 143 (0.752 g, 3.73 mmol) was dissolved in MeOH (8 mL) and tetrahydrofuran (2.5 mL). NIC!? (0.147 g, 1.13 mmol) was added to the solution at 0°C. Then, NaBH4 (0.276 g, 7.30 mmol) was added portionwise to the mixture and the reaction mixture was stirred at 0°C for 20 min and room temperature for 40 min under an Ar atmosphere. The mixture was filtered and the filtrate was evaporated. The residue was suspended with CH2CI2 and the mixture was filtered again. The filtrate was evaporated and dried to afford the pure product (0.503 g, 2.87 mmol, 77%).!H NMR (400 MHz, CDCI3): 5 0.59-0.65 (m, 6H), 0.97 (t, J = 7.9 Hz, 6H), 1 ,45-1.53 (m, 2H), 2.68 (t, 4 = 6.9 Hz, 2H), 3.47 (s, 3H). HRMS (ESIj m / z: calcd for C8H22NOSi: 176.1465 [M+H]+; found: 176.1457.

[0450] Compound 145: Compound 145 was synthesized according to general procedure of addition reaction of axial ligands to A3B-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86) except that compound 144 was used instead of (3- aminopropyl)dimethylethoxysilane.

[0451] Compound 146: Compound 146 was synthesized according to general procedure of alkyl sulfonation of A3B-type silicon phthalocyanine derivatives (compound 48, 69, 87). Yield 8.2% (4 steps).1H NMR (400 MHz, CD3OD): 6 -2.39—2.21 (m, 12H), -1.20— 1.15 (m, 12H), -0.75—0.67 (m, 4H), 1.37 (s, 21 H), 1.72-1.80 (m, 12H), 2.07 (t, 4= 8.1 Hz, 4H), 2.76 (t, J = 6.7 Hz, 12H), 2.85-2.89 (m, 12H), 8.49-8.55 (m, 7H), 9.69-9.75 (m, 2H), 9.77-9.81 (m, 6H). HRMS (ESI ) m / z: calcd for CysHwNioNaaOaoSeSi.*: 907.2318 [M-2Na]2~; found: 907.2349.

[0452] Compound 147: Compound 147 was synthesized according to general procedure of deprotection reaction of triisopropylsilyl group. Yield 61%.1H NMR (400 MHz, CD3OD): 6 -2.39—2.24 (m, 12H), -1.18 (dt, 4= 2.1 , 7.9 Hz, 12H), -0.76—0.68 (m, 4H), 1.73-1.81 (m, 12H), 2.06 (t, J= 8.2 Hz, 4H), 2.76 (t, 4= 6.8 Hz, 12H), 2.85-2.89 (m, 12H), 4.09 (s, 1H), 8.51-8.55 (m, 7H), 9.75 (dd, 4 = 0.6, 7.9 Hz, 1 H), 9.76-9.80 (m, 7H). HRMS (ESI j m / z: calcd for CeeHeaNioNaaC^oSeSis: 829.1651 [M-2Na]2~; found: 829.1683.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0453] si-Tz-iFi / ’OOCIOCOOH-diEtSl: p-Tz-IR700C1 OCOOH-diEtSI was synthesized according to general procedure of click reaction. Yield 83%.!H NMR (400 MHz, CD3OD): 0 -2.41—2.22 (m, 12H), -1.15 (dt, J= 1.3, 8.0 Hz, 12H), -0.84—0.75 (m, 4H), 1.39-1.45 (m, 6H), 1.50-1.58 (m, 4H), 1.61-1.69 (m, 2H), 1.73-1.81 (m, 12H), 2.06 (t, J - 8.2 Hz, 4H), 2.14-2.22 (m, 4H), 2.77 (t,6.9 Hz, 12H), 2.85-2.89 (m, 12H), 4.68 (I, J- 7.4 Hz, 2H),8.52-8.56 (m, 6H), 9.03 (dd, J= 1.4, 8.0 Hz, 1 H), 9.18 (s, 1 H), 9.79-9.81 (m, 5H), 9.82-9.87 (m, 2H) , 10.2 (dd, J = 0.8, 1 .2 Hz, 1 H). HRMS (ESI j m / z\ calcd for CzeH^NiaNasOsjSsSig: 946.7299 [M-2Nap~; found: 946.7336.

[0454] $-Tz-IR700C10SE-diEtSi: p-Tz-IR700C1 OSE-diEtSi was synthesized according to general procedure of synthesis of succinimidyl ester compounds. HRMS (ESI”) m / z: calcd for CsoHioeNnNazC^SeSis: 984.2471 [M-2Na]2”; found: 984.2508.Example 16

[0455] In this example, compounds comprising iso-propyl-substituted silyl groups within the phthalocyanine core were prepared according to the method described below and summarized in Scheme 49.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 49

[0456] Compound 14.9: Compound 148 (2.58 g, 17.1 mmol), allyl bromide (1.68 g, 13.9 mmol) and HaPtCL (4.4 mg, 8.50 pmol) were dissolved in cyclohexane (15 mL) and the mixture was stirred at 100°C under an Ar atmosphere for 11 h. The reaction mixture was evaporated and dried. The crude product was used as is for the next step without further purification.

[0457] Compound 150: Compound 149 was dissolved in pyridine (10 rnL) at 0°C and MeOH (1 .6 mL, 39 mmol) was added dropwise to the solution. The reaction mixture was stirred at4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 room temperature under an Ar atmosphere for 6.5 h. The precipitate was filtered and the filtrate was evaporated. The residue was azeotropic dried with toluene, and the crude product was purified with silica gel column chromatography to afford the product (0.883 g). Compound 150 still contained unknown impurities, but was used for the next step. In some examples, the fallowing characterization data were obtained: HRMS (ESI*) m / z: calcd for CioHsaBrNaOSi: 289.0594 [M+Na]+; found: 289.0587.

[0458] Compound 151: Compound 151 was synthesized according to general procedure of synthesis of azido fatty acid compounds (compound 57, 59, 73). Yield 14% (3 steps).1H NMR (400 MHz, CDCIa): 0 0.67-0.71 (m, 2H), 1.03-1.05 (m, 14H), 1.66-1.73 (m, 2H), 3.26 (t, J= 6.9 Hz, 2H), 3.52 (s, 3H). HRMS (ESI*) m / z: calcd for CwHaNsNaOSi: 252.1503 [M+Na]+; found: 252.1496.

[0459] Compound 152: Compound 151 (442 mg, 1 .93 mmol) was dissolved in MeOH (4.5 mL) and tetrahydrofuran (1 .5 mL). NiCI? (84.6 mg, 0.653 mmol) was added to the solution at 0°C. NaBH4 (161 mg, 4.25 mmol) was added portionwise to the mixture and the reaction mixture was stirred at 0°C for 20 min and room temperature for 40 min under an Ar atmosphere. Then, the mixture was filtered and the filtrate was evaporated. The residue was suspended with CH2CI2 was the mixture was filtered again. The filtrate was evaporated and dried to afford the product (0.319 g, 1 .57 mmol, 81 %).1H NMR (400 MHz, CDCI3): 5 0.62- 0.66 (m, 2H), 1.04 (s, 14H), 1 .54 (br, 2H), 2.71 (br, 2H), 3.52 (s, 3H). HRMS (ESH) m / z: calcd for C^NOSi: 204.1778 [M+H]+: found: 204.1751.

[0460] Compound 153; Compound 153 was synthesized according to general procedure of addition reaction of axial ligands to AsB-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86 of Examples 2, 4, and 7, respectively) except that compound 152 was used instead of (3-aminopropyl)dimethylethoxysilane.

[0461] Compound 154: Compound 154 was synthesized according to general procedure of alkyl sulfonation of AaB-type silicon phthalocyanine derivatives (compound 48, 69, 87, Examples 2, 4, and 7, respectively). Yield 9.7% (4 steps). ^H NMR (400 MHz, CD3OD): 5 -2.70—2.65 (m, 4H), -1.81—1.73 (m, 4H), -1.28 (dd, J = 1.3, 7.4 Hz, 12H), -1.18 (dd, J = 1.3, 7.4 Hz, 12H), -0.25—0.16 (m, 4H), 1.30 (t, 3 = 7.3 Hz, 3H), 1.37 (s, 18H), 1.76-1.83 (m, 12H), 2.02-2.09 (m, 4H), 2.72 (t, 3= 6.6 Hz, 12H), 2.97-3.01 (m, 12H), 8.48 (dd, 3 = 1.3, 8.0 Hz, 1 H), 8.49-8.53 (m, 6H), 9.66-9.70 (m, 2H), 9.72-9.76 (m, 6H). HRMS (ESI*) m / z: calcd for CioHagNOSi: 204.1778 [M-t-H]+: found: 204.1751 .4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0462] Compound 155: Compound 155 was synthesized according to general procedure of deprotection reaction of triisopropylsilyl group (such as shown in Examples 2, 4, and 7).Yield 56%.1H NMR (400 MHz, CDSOD): 5 -2.69 (t, J = 8.5 Hz, 4H), -1.81—1.74 (m, 4H), -1.28 (d, J - 7.4 Hz, 12H), -1.19 (d, J - 7.4 Hz, 12H), -0.25—0.17 (m, 4H), 1.77-1.84 (m, 12H), 2.05 (t, J= 8.1 Hz, 4H), 2.73 (t, J = 6.7 Hz, 12H), 2.98-3.02 (m, 12H), 4.10 (s, 1 H), 8.51-8.53 (m, 7H), 9.70 (dd, J= 0.7, 8.0 Hz, 1 H), 9.72-9.76 (m, 7H). HRMS (ESI") m / z: calcd for CToHsgNioNa^SeSia: 857.1964 [M-2Na]2~; found: 857.1994.

[0463] fi-TzdR700C10COOH-diPrSi: p-Tz-IR700C1 OCOOH-diPrSi was synthesized according to general procedure of click reaction (such as shown in Examples 2, 4, and 7), Yield 74%.1H NMR (400 MHz, CD3OD): 6 -2.63 (t, J- 8.5 Hz, 4H), -1.82—1.75 (m, 4H), -1.25 (dd, J- 1.1 , 7.4 Hz, 12H), -1.17 (d, J = 7.4 Hz, 12H), -0.30—0.21 (m, 4H), 1.39-1.45 (m, 6H), 1.51-1.58 (m, 4H), 1.62-1.69 (m, 2H), 1.76-1.83 (m, 12H), 2.05 (t, J= 8.0 Hz, 4H), 2.16-2.22 (m, 4H), 2.72 (t, 7 - 6.7 Hz, 12H), 2.97-3.01 (m, 12H), 4.68 (t, J - 7.4 Hz, 2H), 8.52 (dd, J= 2.9, 5.8 Hz, 6H), 8.99 (dd, 5 - 1.4, 8.0 Hz, 1 H), 9.13 (s, 1 H), 9.75 (dd, J - 2.9, 5.8 Hz, 5H), 9.78-9.82 (m, 2H), 10.2 (dd, J= 0.8, 1.2 Hz, 1 H). HRMS (ESI-) m / z: calcd for CsoHnohkNagOasSeSis: 974.7612 [M-2Na]2~; found: 974.7650.

[0464] / 3-TZ-IR700C1 OSE-diPrSi: f>-Tz-IR700C1 OSE-diPrSi was synthesized according to general procedure of synthesis of succinimidyl ester compounds, such as shown in Examples 2, 4, and 7). HRMS (ESI-) m / z: calcd for C^HmNuNasOgASeSis: 1012.2784 [M-2Na]2"; found: 1012.2823.Example 17

[0465] In this example, compounds comprising phenyl-substituted silyl groups within the phthalocyanine core were prepared according to the method described below and summarized in Scheme 50.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 50

[0466] Compound 156: Compound 141 (2.99 g, 12.3 mmol) was dissolved in tetrahydrofuran (25 mL) under an Ar atmosphere. PhMgBr (3 M in EtaO, 9 mL, 27 mmol) was added to the solution and the mixture was stirred at 60°C for 3 h. AcOEt was added to the reaction mixture and the organic layer was washed with H2O and saturated NaClaq, dried over NasSCU filtered and evaporated. The crude product was purified with silica gel column chromatography to afford the pure product (3.38 g, 10.1 mmol, 82%).1H NMR (400 MHz, CDCI3): 6 1.26-1.30 (m, 2H), 1.93-2.00 (m, 2H), 3.41 (t, 6.8 Hz, 2H), 3.54 (s, 3H), 7.37-4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20257.46 (m, 6H), 7.57-7.59 (m, 4H). HRMS (ESI+) m / z: calcd for CisHigBrNaOSI: 357.0281 [M+Na]* ; found: 357.0269.

[0467] Compound 157: Compound 157 was synthesized according io general procedure of synthesis of azido fatty acid compounds (compound 57, 59, 73, such as in Examples 2 and 4). Yield quant.1H NMR (400 MHz, CDCh): 5 1 .17-1 .21 (m, 2H), 1.67-1.75 (m, 2H), 3.26 (t, J - 6.9 Hz, 2H), 3.54 (s, 3H), 7.37-7.44 (m, 6H), 7.57-7.59 (m, 4H). HRMS (ESI+) m / z: calcd for Ci6Hi9N3NaOSi: 320.1 190 [M+Na]+; found: 320.1 179.

[0468] Compound 158.' Compound 157 (904 mg, 3.04 mmol) was dissolved in MeOH (9 mL) and tetrahydrofuran (3 mL). NiCI2(127 mg, 0.976 mmol) was added to the solution at 0°C. NaBH4(234 mg, 6.1 mmol) was added portionwise to the mixture and the reaction mixture was stirred at 0c’C for 20 min and room temperature for 40 min under an Ar atmosphere. Then, the mixture was filtered and the filtrate was evaporated. The residue was suspended with CH2CI2 was the mixture was filtered again. The filtrate was evaporated and dried to afford the product (576 mg, 2.12 mmol, 70%).!H NMR (400 MHz, CDCI3): 6 1.15 (t, J = 8.4 Hz, 2H), 1.52-1 .59 (m, 2H), 2.69 (br, 2H), 3.54 (s, 3H), 7.36-7.43 (m, 6H), 7.57-7.60 (m, 4H). HRMS (ESI+) m / z: calcd for Ci6H22NOSi: 272.1465 [M+H]+; found: 272.1456.

[0469] Compound 159: Compound 159 was synthesized according to general procedure of addition reaction of axial ligands to A3B-type silicon phthalocyanine dihydroxide derivatives (compound 47, 68, 86, such as in Examples 2, 4, and 7, respectively) except that compound 179 was used instead of (3-aminopropyl)dlmethylethoxysilane.

[0470] Compound 16’0: Compound 160 was synthesized according to general procedure of alkyl sulfonation of A3B-type silicon phthalocyanine derivatives (compound 48, 69, 87, such as in Examples 2, 4, and 7, respectively). Yield 4.5% (4 steps).NMR (400 MHz, CD3OD): 5 -1 .73—1.64 (m, 4H), -0.85—0.65 (m, 4H), 1.39 (s, 21 H), 1 .42-1.50 (m, 12H), 2.52-2.61 (m, 24H), 4.80 (t, J = 6.6 Hz, 8H), 6.36-6.41 (m, 8H), 6.74-6.81 (m, 4H), 8.47-8.56 (m, 7H), 9.52 (s, 1 H), 9.55—9.58 (m, 1 H), 9.62—9. 46 (m, 2H), 9.66—9.69 (m, 1 H), 9.71—9.78 (m, 3H). HRMS (ESI-) m / z: calcd for Cgi HWlioNaaOajSeSh: 1003.2318 [M-2Na]2-; found: 1003.2354.

[0471] Compound 161. ' Compound 161 was synthesized according to general procedure of deprotection reaction of tri isopropylsilyl group, such as shown in Examples 2, 4, and 7, respectively. Yield 55%.1H NMR (400 MHz, CD3OD): 6 -1.70—1.65 (m, 4H), -0.83—0.75 (m, 4H), 1 .43-1.51 (m, 12H), 1 .72 (t, J = 8.3 Hz, 4H), 2.53-2.57 (m, 12H), 2.60 (t, J - 6.8 Hz, 12H), 4.11 (s, 1 H), 4.80 (td, J= 1.6, 7.7 Hz, 8H), 6.38 (dt, J = 1.1 , 7.7 Hz, 8H), 6.75-6.804239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025(m, 4H), 8.50-8.56 (m, 7H), 9.59 (dd, J= 0.6, 7.9 Hz, 1 H), 9.63-9.75 (m, 7H). HRMS (ESI-) m / z: calcd for C82H64NioNa2020S6Si3: 925.1651 [M-2Na]2~: found: 925.1687.

[0472] p~Tz~IFl700C1 OCOOH-diPhSi: p-Tz-IR700C1 OCOOH-diPhSi was synthesized according to general procedure of click reaction, such as shown in Examples 2, 4, and 7, respectively. Yield 96%.1H NMR (400 MHz, CD3OD): 5 -1.63 (t, J= 7.3 Hz, 4H), -0.88- “0.75 (m, 4H), 1.43-1.50 (m, 18H), 1.53-1.62 (m, 4H), 1.63-1.72 (m, 6H), 2.17-2.21 (m, 4H), 2.51-2.56 (m, 12H), 2.61 (t, J - 6.9 Hz. 12H), 4.69 (t. J = 7.4 Hz, 2H), 4.80 (Id, J- 1.2, 7.8 Hz, 8H), 6.38 (dt, J= 1.0, 7.8 Hz, 8H), 6.73-6.79 (m, 4H), 8.51-8.55 (m, 6H), 9.01 (dd, J = 1.4, 8.0 Hz, 1 H), 9.19 (s, 1 H), 9.67-9.73 (m, 7H), 10.1 (dd, J= 0.8, 1.2 Hz, 1H). HRMS (ESI”) m / z: calcd for CgzHiosNnNasO^SsSis: 1042.7299 [M-2Na]2-; found: 1042.7340.

[0473] 0-Tz-IR7OOC1OSE-diPhSi: p-Tz-IR700C1 OSE-diPhSi was synthesized according to general procedure of synthesis of succinimidyl ester compounds, such as shown in Examples 2, 4, and 7, respectively. HRMS (ESI j m / z: calcd for CgeHioGNuNagO^SeSis: 1080.2471 [M~2Na]2”; found: 1080.2514.Example 18

[0474] In this example, compounds comprising a pyridyl-containing linker group were prepared using a Heck reaction with p-Br SiPc-NH?. and a pyridine comprising a linker as detailed below and summarized in Scheme 51.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 51

[0475] Procedure for making Compound 163: Compound 162 (2-bromo-5-hydroxypiridine, 2.10 g, 12.1 mmol), methyl 6-bromohexanoate (2.32 g, 11.1 mmol) and potassium carbonate (4.51 g, 32.7 mmol) were dissolved in acetone (20 mL), and the mixture was refluxed for 14 hours. After the addition of 1 M HCI and brine, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over NasSCh, filtered and evaporated. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate, 3 / 1 to 2 / 1 ) to give compound 163 (3.19 g, 10.6 mmol, y. 95%) as a colorless oil.SH NMR (400 MHz,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025CDCh) 6 8.03 (d, J = 3.0 Hz, 1 H) , 7.35 (d, J = 8.7 Hz, 1 H), 7.09 (dd, J = 8.7, 3.0 Hz, 1 H) , 3.98 (t, J- 6.4 Hz, 2H), 3.67 (s, 3H), 2.35 (t, J - 7.4 Hz, 2H), 1.85-1 .78 (m, 2H), 1.74-1.67 (m, 2H), 1 .54-1 .47 (m, 2H). LRMS (ESP) m / z: [M+H]+calcd for CiaHieBrNOs 302.0392; found 302. HRMS (ESH) m / z: calcd for C?H-GBrNO3: 302.0386found: 302.0382.

[0476] Procedure for making Compound 164: Compound 163 (1 .52 g, 5.1 mmol}, vinylboronic acid pinacol ester (1 .25 g, 8.1 mmol), cesium fluoride (2.29 g, 15.1 mmol) and bis(triphenylphosphine)palladium(ll) dichloride (76 mg, 506 pmmol) were dissolved in dioxane / HgO (10 mL / 5 mL), and the mixture was stirred at 80 °C under an Ar atmosphere for 21 hours. After the addition of brine, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over NaaSCu, filtered and evaporated. The residue was purified by silica gel column chromatography (eluent: hexane / ethy! acetate, 1 / 0 to 3 / 1 ) to give compound 164 (565 mg, 2.27 mmol, y. 45%) as a colorless oil. ' H NMR (400 MHz, CDCh) 5 8.23 (d, J - 2.8 Hz, 1 H), 7.28 (d, J- 8.6 Hz, 1 H), 7.13 (dd, J- 8.6, 2.8 Hz, 1 H), 6.77 (dd, J- 17.5, 10.9 Hz, 1 H), 6.02 (dd, J - 17.5, 1.3 Hz, 1 H), 5.35 (dd, J == 10.9, 1 .3 Hz, 1 H), 4.01 (t, J - 6.4 Hz, 2H), 3.68 (s, 3H), 2.36 (t, J = 7.4 Hz, 2H), 1.86-1.78 (m, 2H), 1.75-1.67 (m, 2H), 1 .55-1 .47 (m, 2H). LRMS (ESI4) m / z: [M+H]+calcd tor CuHx.NCh 250.1443; found 250. HRMS (ESI+) m / z: calcd for C-H20NO3: 250.1438 [M+H]T found: 250.1449.

[0477] Compound 165: Compound 165 was synthesized by the same method as compound 76.

[0478] Compound 166: Compound 166 was synthesized by the same method as compound 77. LRMS (ESI): m / z calc, for C74H95N: ■0,<<S;-.S:i[M+2H-4Na]2", 890.71225; found, 891 . HRMS (ESI") m / z: calcd for Cy.HceNu NaaOasSsSis: 912.6942 [M-2Na]2~; found: 912.6976.

[0479] Pyr-IR700 C6COOH: Pyr-IR700 C6COOH was synthesized by the same method as Styrl -I R700 C6COOH (y. 0.26% in 5 steps). " H NMR (400 MHz, CD3OD): 5 9.83 (s, 1 H), 9.75-9.73 (m. 1 H), 9.69-9.66 (m, 5H), 9.64 (d, J - 8.1 Hz, 1 H), 8.63 (d, J - 8.1 Hz, 1 H), 8.44-8.40 (m, 6H), 8.26 (d, J = 2.9 Hz, 1 H), 8.09 (d, J= 16.1 Hz, I N), 7.87 (d, J = 16.1 Hz, 1 H), 7.87 (d, J - 8.7 Hz, 1 H), 7.44 (d, J- 8.7, 2.9, 1 H), 4.08 (t, J - 6.5 Hz, 2H), 2.69-2.64 (m, 24H), 2.15 (t, J = 7.5 Hz, 2H), 1.93-1 .89 (m, 4H), 1.84-1 .78 (m, 2H), 1.68-1.58 (m, 14H), 1.53-1.45 (m, 2H), -1.01 —1.03 (m, 4H), -2.21—2.25 (m, 4H), -2.87 (s, 12H). LRMS (ESI): m / z calc, for C / sHgsN^OaaSeSis [M-r3H-5Na]2", 884.70445; found, 884. HRMS (ESI") m / z: calcd for CysHsoNnNasCfeSeSis: 916.6774 [M-2Na]2"; found: 916.6810.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0480] Pyr-IR700 C6SE: Pyr-IR700 C6SE was synthesized by the same method as Styrl- IR700 C6SE. LRMS (ESI): m / z calc, for Cy / HgeN^C^SeSis [M+2H~4Na]2", 932.21265; found,933. HRMS (ESI“) m / z: calcd for CTsHgoNnNasOzsSsSia: 916.6774 [M-2Na]?-; found:916.6810.Example 19

[0481] In this example, compounds comprising an amide-containing linker group were prepared using a Heck reaction with p-Br SiPc-NHg and an amide-terminated linker group as detailed below and summarized in Scheme 52.Scheme 524239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0482] Procedure for making Compound 168: Thionyl chloride (6 mL, 82.2 mmol) was added dropwise to a stirred solution of compound 167 (7-aminoheptanoid acid, 2.31 mg, 15.9 mmol) and methanol (17 mL) at 0 °C. The resulting solution was then warmed to room temperature and stirred for 3 hours. The solvent and thionyl chloride were then removed under reduced pressure. Compound 168 (3.05 g, 15.6 mmol, y. 98%) were isolated as a white solid.1H NMR (400 MHz, MeOD) 5 3.67 (s, 3H), 2.82 (t, J = 7.5 Hz, 2H), 2.25 (t, J = 7.3 Hz, 2H), 1 .59-1.50 (m, 4H), 1 .36-1 .24 (m, 4H). LRMS (ESP) m / z: [M-CI]+calcd for CaHisNOz 160.1338; found 160. HRMS (ESH) m / z: calcd for C8H18NO2: 160.1332 [M-CI]+; found: 160.1339.

[0483] Procedure for making Compound 169: Acryloyl chloride (10.2 g, 1 1 .1 mmol) was added dropwise to the stirred ice-cold dispersion of compound 168 (1 .08 g, 5.5 mmol) and triethylamine (2.54 g, 25.1 mmol) in CH3CN (7.5 mL). The resulting solution was then warmed to room temperature and stirred overnight. After the addition of brine, the reaction mixture was extracted with CH2CI2. The organic layer was dried over NajSOi, filtered and evaporated to give compound 169 (1 .05 g, 4.92 mmol, y. 89%) as a yellow oil.1H NMR (400 MHz, MeOD) 8 6.23 (d, J - 8.3 Hz, 1 H), 6.22 (d, J - 3.7 Hz, 1 H), 5.65 (dd, J - 8 3. 3.7 Hz, 1 H), 3.67 (s, 3H), 3.29-3.22 (m, 2H), 2.34 (d, 7.4, 2H), 1 .67-1 .52 (m, 4H), 1 .42-1 .31 (m,4H). LRMS (ESH) m / z: [M+H]~ calcd for C11 H20NO2 214.1443; found 214. HRMS (ESH) m / z: calcd for C- H?,NO:;. 214.1438 [M+Hp ; found: 214.1434.

[0484] Compound 170: Compound 170 was synthesized by the same method as compound 101.

[0485] Compound 171: Compound 171 was synthesized by the same method as compound 102. LRMS (ESI") m / z: [M*2H-4Na]z- calcd for C71 H95N, ■C%ScS;3. 872.71225; found, 873. HRMS (ESH) m / z: calcd for C71 H93N H NaaOaSeSfo 894.6942 [M-2Na]2": found: 894.6982.

[0486] IR700-Amd-COOH: IR / OO-Amd-COOH was synthesized by the same method as IR700-alkene-COOH (y. 0.32% in 5 steps). " H NMR (400 MHz, CD3OD): 6 9.90 (s, 1 H), 9.76-9.74 (m, 1 H), 9.70-9.65 (m, 6H), 8.61 (d, J - 8.1 Hz, 1 H), 8.47-8.40 (m, 6H), 8.13 (d, J = 15.7 Hz, 1 H), 7.39 (d, J = 15.7, 1 H), 3.36 (t, J = 7.7 Hz, 2H), 2.70-2.65 (m, 24H), 2.14 (t, J = 7.6 Hz, 2H), 1 .93-1 .89 (m, 4H), 1 .66-1 .60 (m, 16H), 1 .47-1 .37 (m, 4H), -1 .02 (m, 4H), -2.21—2.25 (m, 4H), -2.87 (s, 12H), LRMS (ESI") m / z: [M+3H-5Na]2" calcd for C70H93N1 lOasSsSis, 865.7045; found, 866. HRMS (ESI-) m / z: calcd for C / oHgoNii NasOasSeSis: 898.6774 [M-2Na]2“; found: 898.6816.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0487] IR700-Amd-SE: IR700-Amd-SE was synthesized by the same method as IR700- alkene-SE. LRMS (ESI") m / z: [M+2H-4Na]2’ calcd for Cy^HgeNiaOasSoSis, 914.21265; found,915. HRMS (ESI“) m / z: calcd for Cj^NuNazOssSeSis: 936.1946 [M-2Na]?-; found:936.1991 .Example 20

[0488] In this example, compounds comprising a sulfanamide-containing linker group were prepared using a Heck reaction with p-Br SiPc-NIHs and a sulfonamide-terminated linker group as detailed below and summarized in Scheme 53.Scheme 534239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0489] Procedure for making Compound 172: The solution of 2-chloroethanesulfonyl chloride (795 mg, 4.9 mmol) in CH2CI2(10 mL) was added dropwise to the stirred ice-cold dispersion of compound 168 (597 mg, 3.1 mmol) and triethylamine (1.15 g, 11.4 mmol) in CH2CI2 (20 mL). The resulting solution was then warmed to room temperature and stirred overnight. Then it was evaporated at reduced pressure, the residue was triturated with water, acidified to pH 3, and extracted with ethyl acetate. The organic layer was dried over NapSCL, filtered and evaporated. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate, 1 / 0 to 2 / 1 ) to give compound 172 (678 mg, 2.72 mmol, y. 89%).!H NMR (400 MHz, MeOD) 5 6.64 (dd, J - 16.6, 10.0 Hz, 1 H), 6.13 (d, J = 16.6 Hz, 1 H). 5.96 (d, J = 16.6 Hz, 1 H), 3.67 (s, 3H), 2.94 (t, 7.0 Hz, 2H), 2.34 (t, 7.4 Hz, 2H), 1.67-1.60 (m, 2H), 1.58-1.51 (m, 2H), 1.43-1.31 (m, 4H). LRMS (ESP) m / z: [M+H]+calcd for CioH^NCuS 250.1113; found 250. HRMS (ESP) m / z. calcd for C10H20NO4S: 250.1108 [M+H]+; found: 250.1 107.

[0490] Compound 173: Compound 173 was synthesized by the same method as compound 101.

[0491] Compound 174: Compound 174 was synthesized by the same method as compound 102. LRMS (ESI—) m / z: [M+2H~4Na]2- calcd for CzoHssNnOaSzSis, 890.69575; found, 891 . HRMS (ESI ) m / z: calcd for CyoHseNnNagO^SzSis: 912.6777 [M-2Na]2; found: 912.6820.

[0492] IR700-SA-COQH: IH700-SA-COOH was synthesized by the same method as IR700-alkene-COOH (y. 0.08% in 5 steps).!H NMR (400 MHz, CD3OD): 59.90 (s, 1 H), 9.75-9.66 (m, 7H), 8.61 (d, J - 8.2 Hz, 1 H), 8.45-8.41 (m, 6H), 8.05 (d, J = 15.5 Hz, 1 H), 7.71 (d, J= 15.5, 1 H), 2.70-2.62 (m, 26H), 2.25 (t,7.4 Hz, 2H), 1.94-1.90 (m, 4H), 1.63-1.34 (m, 20H), -0.94—0.99 (m, 4H), -2.25—2.29 (m, 4H), -2.88 (s, 12H). LRMS (ESH) m / z: [M+3H-5Na]2~ calcd for C69H93N11O24S7S13, 883.6880; found, 884. HRMS (ESI”) m / z: calcd for CegHsoNiiNasC^SzSis: 916.6609 [M-2Na]2~; found: 916.6649.

[0493] IR700-SA-SE: 1P700-SA-SE was synthesized by the same method as IR700-alkene- SE. LRMS (ESI-) m / z: [M+2H-4Na]2- calcd for932.1961 ; found, 933.HRMS (ESL) m / z: calcd for C73H94Ni2Na2O26S7Si3: 954.1781 [M-2Na]2”; found: 954.1826.Example 21

[0494] In this example, compounds comprising a PEG linker group were prepared using a Heck reaction with p-Br SiPc-NH?. and a PEG linker group as detailed below and summarized in Scheme 54.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 54

[0495] Procedure for making Compound 176: Compound 175 (PEG3-carboxylic acid tertbutyl ester, 2.35 g, 10.0 mmol) was slowly added to a stirred suspension of NaH (90%; 325 mg, 12.2 mmol) in dry THF (17 mL) under an Ar atmosphere at 0 °C. after stirring for 30 min, the solution was allowed to warm up to room temperature. Allyl bromide (1 .89 g, 15.6 mmol) was added dropwise, and the resulting suspension was stirred at room temperature for 2 hours. The reaction was quenched by adding water and the organic layer was dried over NasSCXi, filtered and evaporated. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate, 10 / 1 ) to give compound 176 (1.05 g, 3.81 mmol, y. 38%).1H NMR (400 MHz, CDCh) 5 5.92 (ddt, J = 17.2, 10.4, 5.7 Hz, 1 H), 5.27 (ddt, J = 17.2, 1.7, 1.4 Hz, 1 H), 5.18 (ddt, J - 10.4, 1.7, 1.4, 1 H), 4.02 (dt, J = 5.7, 1.4 Hz, 2H),4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20253.71 (t, J= 6.6 Hz, 2H), 3.67-3.59 (m, 8H), 2.50 (t, J = 6.6 Hz, 2H), 1.45 (s, 9H). LRMS (ESI4) m / z: [M+Na]* calcd for C14H26NaO5297.1678; found 297. HRMS (ESI") m / z: calcd for C73H94N12Na2O26S7Si3: 954.1781 [M-2Na]?"; found: 954.1826.

[0496] Procedure for making Compound 177: Compound 176 (290 mg, 1 .06 mmol) was dissolved in CH2CI2 (7 mL). Trifluoroacetic acid (2.6 mL) was added and the solution was stirred at room temperature for 3 hours. Once the reaction was finished, the solution was coevaporated with toluene three times (20 mL each) to remove trifluoroacetic acid and solvent. After drying under vacuum, compound 177 (231 mg, 1 .06 mmol, y. quant) was directly used in next step without further purification.1H NMR (400 MHz, CDCh) 6 5.92 (ddt, J = 17.2, 10.4, 5.8 Hz, 1 H), 5.28 (ddt, J= 17.2, 1 .6, 1.4 Hz, 1 H), 5.17 (ddt, J= 10.4, 1 .6, 1.4, 1 H), 4.04 (dt, J - 5.8, 1 .4 Hz, 2H), 3.79 (t, J - 6.1 Hz, 2H), 3.70-3.61 (m, 8H), 2.66 (t, J - 6.1 Hz, 2H). LRMS (ESH) m / z: [M+H]+calcd for CI0HI9O5219.1232; found 219. HRMS (ESH) m / z: calcd for CI0HI9O5: 219.1227 [M+H]+; found: 219.1221 .

[0497] Procedure for making Compound 178: T o the compound 177 (653 mg, 3.0 mmol) were added CHaGL (8 mL), ethanol (350 pL, 6 mmol) and DMAP (48 mg, 393 pmol). After cooling the solution to 0 °C, DCC (710 mg, 3.4 mmol) was added. The mixture was stirred at 0 °C for 5 min and then at room temperature for 4 hours. The reaction mixture was extracted with CH2CI2, washed with 0.5 M HCI and saturated NaHCOs solution sequentially. The organic layer was dried over NapSCk, filtered and evaporated. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate, 10 / 1 to 10 / 2) to give compound 178 (690 mg, 2.80 mmol, y. 94%).1H NMR (400 MHz, CDCh) 6 5.92 (ddt, , / = 17.2, 10.4, 5.7 Hz, 1 H), 5.27 (ddt, J - 17.2, 1 .7, 1.5 Hz, 1 H), 5.18 (ddt, J = 10.4, 1 .7, 1.5, 1 H), 4.15 (q, J= 7.1 Hz, 2H), 4.02 (dt, J = 5.7, 1 .5 Hz, 2H), 3.76 (t, J = 6.5 Hz, 2H), 3.67- 3.59 (m, 8H), 2.59 (t, 6.5 Hz, 2H), 1.26 (t, J= 7.1 Hz, 3H). LRMS (ESH) m / z: [M+H]+calcd for C247.1545; found 247. HRMS (ESH) m / z: calcd for C12H23O5: 247.1540 [M+H]+: found: 247.1534.

[0498] Compound 179: Compound 179 was synthesized by the same method as compound 101.

[0499] Compound 180: Compound 180 was synthesized by the same method as compound 102. LRMS (ESI") m / z: [M+2H-4Na]2~ calcd for CraHosNioChsSeSb , 889.2174; found, 890.

[0500] IR700-PEG-COOH: 1R700-PEG-COOH was synthesized by the same method asIR700-alkene-COOH (y. 0.15% in 5 steps).9.66 (m,4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20257H), 9.61 (d, J = 8.1 Hz, 1 H), 8.52 (dd, J= 8.1 , 1.2 Hz, 1 H), 8.46-8.40 (m, 6H), 7.36 (d, J = 16.0 Hz, 1 H), 7.05 (dt, J - 16.0, 5.8 Hz, 1 H), 4.44 (d, J = 5.8 Hz, 2H), 3.80-3.61 (m, 10H), 2.74-2.64 (m, 24H), 2.42 (t, J = 6.8 Hz, 2H), 1 .94-1.90 (m, 4H), 1 .64-1 .60 (m, 12H), -1.00- -1.03 (m, 4H), -2.21—2.25 (m, 4H), -2.87 (s, 12H). LRMS (ESH) m / z: [M+3H-5Na]2- calcd for C7oH94Nio025S6Sis [M+3H-5Na]2~ 875.20175; found, 876. HRMS (ESI") m / z: calcd for C7oH9i NwNa3025S6Sl3: 908.1747 [M-2Na]z~; found: 908.1784.

[0501] IR700-PEG-SE: SR700-PEG-SE was synthesized by the same method as IR700- alkene-SE. LRMS (ESI-) m / z: [M+2H-4Na]2~ calcd for CyaHgyNnO^SsSis, 923.7099: found, 924. HRMS (ESI") m / z: calcd for Cy^Nii NaaOsySeSis: 945.6919 [M-2Na]2~; found: 945.6963.Example 22

[0502] In this example, compounds comprising an amide PEG linker group were prepared using a Heck reaction with p-Br SiPc-NH2and an amide PEG linker group as detailed below and summarized in Scheme 55.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Scheme 55

[0503] Procedure for making Compound 182: Compound 181 ((Boc-amino)-PEG3-C2- carboxylic acid, 282 mg, 0.9 mmol) was dissolved in CH2CI2 (4.5 mL). Trifluoroacetic acid (2.2 mL) was added and the solution was stirred at room temperature for 2 hours. Once the reaction was finished, the solution was co-evaporated with toluene three times (20 mL each) to remove trifluoroacetic acid and solvent. After drying under vacuum, crude compound 182 (361 mg) was directly used in next step without further purification. LRMS (ESI*) m / z: [M+H]+calcd for C9H20NO5222.1341 ; found 222. HRMS (ESP) m / z: calcd for C9H20NO5: 222.1336 [M+H]+; found: 222.1317.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0504] Procedure for making Compound 183: Thionyl chloride (4.1 mL, 56.2 mmol) was added dropwise to a stirred solution of crude compound 182 (1 .56 g) and methanol (6 mL) at 0 °C. The resulting solution was then warmed to room temperature and stirred for 4 hours. The solvent and thionyl chloride were then removed under reduced pressure. Compound 183 (1010 mg, 3.72 mmol, y. 97.8% (2 steps)) were isolated as a white solid.NMR (400 MHz, MeOD) 6 3.80-3.66 (m, 12H), 3.65 (s, 3H), 3.15 (t, 5.06 Hz, 2H), 2.62 (t, J= 6.10Hz, 2H). LRMS (ESI4) m / z: [M-CI]4calcd for C10H22NO5236.1498; found 236. HRMS (ESI4) m / z: calcd for C10H22NO5: 236.1425 [M-Ci]+; found: 236.1469.

[0505] Procedure for making Compound 184: Acryloyl chloride (791 mg, 8.7 mmol) was added dropwise to the stirred ice-cold dispersion of compound 183 (982 mg, 3.6 mmol) and triethylamine (1.79 g, 17.7 mmol) in CH3CN (6 mL). The resulting solution was then warmed to room temperature and stirred overnight. After the addition of brine, the reaction mixture was extracted with GH2CI2. The organic layer was dried over NaaSOa, filtered and evaporated to give compound 184 (430 mg, 1.49 mmol, y. 41%) as a yellow oil.1H NMR (400 MHz, CDCh) 8 6.42 (br, 1 H), 6.30 (dd, J= 17.0, 1.6 Hz, 1 H), 6.14 (dd, J= 17.0, 10.2 Hz, 1 H), 5.63 (dd, J - 10.2, 1.6 Hz, 1 H), 3.77 (t, J = 6.4 Hz, 2H), 3.69 (s, 3H), 3.64-3.51 (m, 12H), 2.61 (t, 2H). LRMS (ESI*) m / z: [M+Hp calcd for Ci3H24NO6290.1604: found 290. HRMS (ESI+) m / z: calcd for C;3H24NO6: 290.1598 [M+H]+; found: 290.1593.

[0506] Compound 185: Compound 185 was synthesized by the same method as compound 101.

[0507] Compound 186: Compound 186 was synthesized by the same method as compound 102. LRMS (ESI") m / z: [M+2H-4Na]2” calcd for CzaRggN-OseScSis, 910.7203; found, 911 . HRMS (ESI j m / z: calcd for C73H37NiiNa2O26S6Si3: 932.7022 [M-2Na]z~; found: 932.7067.

[0508] IR700-.Amd-PEG~COOH: IR700-Amd-PEG-COOH was synthesized by the same method as IR700-alkene-COOH (y. 0.10% in 5 steps).1H NMR (400 MHz, CD3OD): 69.91 (s, 1 H), 9.75-9.73 (m, 1 H), 9.67-9.63 (m, 6H), 8.53 (d, J = 8.2 Hz, 1 H), 8.43-8.39 (m, 6H), 8.12 (d, J = 15.7 Hz, 1 H), 7.44 (d, J- 15.7, 1 H), 3.68-3.51 (m, 14H), 2.67-2.60 (m, 24H), 2.38 (t, J= 6.7 Hz, 2H), 1 .92-1 .87 (m, 4H), 1 .64-1 .58 (m, 12H), -1.04—1 .06 (m, 4H), -2.24—2.28 (m, 4H), -2.89 (s, 12H). LRMS (ESI") m / z: [M+3H-5Na]2" calcd for C72H97Ni,O26S6Si3, 903.71245; found, 904. HRMS (ESI") m / z: calcd for C72H94Ni!Na3O26S6Si3: 936.6854 [M-2Na]2~; found: 936.6897.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0509] :R700- Amd- PEG SE: IF!70Cr-Amd-PEG-SE was synthesized by the same method as IR700-alkene-SE. LRMS (ESI") m / z: [M+2H~4Na]2" calcd for CzeHiooNiaOasSsSis, 952.22065; found, 953. HRMS (ESI") m / z: calcd for C76H98N12Na2O28S6Si3: 974.2026 [M-2Na]2~: found: 974.2068.Example 23

[0510] In this example, dimer precursor compounds were made. The compounds were made according to the method detailed below and summarized in Schemes 56 and 57.Results from analyzing these compounds using IR spectroscopy are shown in FIG. 1 .Scheme 56

[0511] Procedure for making Compound 96: Compound 95 (1 ,2,4,5-tetracyanobenzene, 1 .00 g, 5.61 mmol) and NaOMe (128 mg, 2.37 mmol) was stirred at room temperature in 2 mol / L ammonia methanol solution (50 mL) for 1 hour. The product was insoluble in methanol and precipitated out to afford compound 96 (843 mg, y, 71 %), and dried in vacuo.1H NMR (400 MHz, CDaOD): 5 7.83 (s, 2H), LRMS (ESI j m / z: [M+H]+calcd for CIOH9N6, 213; found, 213.

[0512] Procedure for making Compound 97: Compound 96 (103 mg, 484 pmol), SiCk (833 mg, 4.90 mmol) and 1 ,3-diiminoisoindo!ine (686 mg, 4.72 mmol) were dissolved in quinoline (10 mL), and the mixture was refluxed for 2 hours under an Ar atmosphere. After the mixture was cooled to room temperature, 1 mol / L NaOHaq (10 mL) was added, and the mixture was refluxed for 1 hour. The product was recovered by filtration, washed with MeOH, and dried in vacuo to afford compound 97 (591 mg). The crude product was used for the next step without further purification.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025

[0513] Procedure for making Compound 98: Compound 97 (199 mg) and 3- aminopropyldimethylethoxysilane (327 mg, 2.03 mmol) were dissolved in pyridine (80 mL), and the mixture was refluxed for 6 hours under Ar atmosphere. The reaction mixture was concentrated by rotary evaporation. The residue was diluted, filtered, washed with a HaO / EtOH solution (2:1 ), and dried in vacuo to afford compound 98 (205 mg). The crude product was used for the next step without further purification.

[0514] Procedure for making Di-SiPc (Xdye-2): Compound 98 (101 mg), 1 ,3- propanesultone (978 mg, 8.01 mmol), and A / ,A / -diisopropylethylamine (1.13 g, 8.74 mmol) were dissolved in MeOH (6 mL), and the mixture was stirred at 50 °C for 48 hours under an Ar atmosphere. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent B (CH3CN) (A / B = 70 / 30 to 50 / 50 in 40 min, 50 / 50 to 0 / 100 in 5 min. The product was desalted with a Sep-Pak Cl 8 cartridge and cation-exchange resin, affording the product (3.4 mg, 1.1 pmol, y. 1 .4% in 3 steps as a sodium salt).5H NMR (400 MHz, CD3OD): 5 11.76 (s, 2H), 10.06 (d, J= 7.5 Hz, 12H), 9.74-9.69 (m, 8H), 8.56 (t, J= 7.5 Hz, 4H), 8.48 (t, J = 7.7 Hz, 4H), 8.43 (dd, J= 8.5, 2.9 Hz, 4H), 2.70-2.66 (m, 24H), 2.59 (t, J - 6.7 Hz, 24H), 1 .97-1 .93 (m, 8H), 1 .57-1 .55 (m, 24H), -0.77—0.78 (m, 8H), -2.16—2.21 (m, 8H), -2.72 (s, 24H). HRMS (ESI”) m / z: calcd for CiuHueNsoNa^oS^SIs: 769.6221 [M-4Na]4-; found: 769.6166.Scheme 57

[0515] Procedure for making Compound 99: Compound 96 (101 mg, 475 pmoi), SiCk (670 mg, 3.94 mmoi) and 1 ,3-diiminobenz[f|isoindoline (737 mg, 3.78 mmol) were dissolved in4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025 quinoline (10 mL), and the mixture was refluxed for 2 hours under an Ar atmosphere. After the mixture was cooled to room temperature, 1 mol / L NaOHaq (10 mL) was added, and the mixture was refluxed for 1 hour. The product was recovered by filtration, washed with MeOH, and dried in vacuo to afford compound 99 (801 mg). The crude product was used for the next step without further purification.

[0516] Procedure for making Compound WO: Compound 99 (396 mg) and 3- aminopropyldimethyleihoxysilane (480 mg, 2.97 mmol) were dissolved in pyridine (100 mL), and the mixture was refluxed for 8 hours under Ar atmosphere. The reaction mixture was concentrated by rotary evaporation. The residue was diluted, filtered, washed with a FfeO / EtOH solution (1 :1), and dried in vacuo to afford compound 100 (333 mg). The crude product was used for the next step without further purification.

[0517] Procedure for making Di-SiNPc (Xdye-3): Compound 100 (204 mg), 1 ,3- propanesultone (1.64 g, 13.4 mmol), and A / ,A / -diisopropylethylamine (1 .88 g, 14,5 mmol) were dissolved in MeOH (10 mL), and the mixture was stirred at 50 °C for 48 hours under an Ar atmosphere. The product was purified by an HPLC system with a reverse-phase column, using eluent A (H2O, 0.1 M triethylammonium acetate) and eluent 8 (CH3CN) (A / B = 70 / 30 to 50 / 50 in 40 min, 50 / 50 to 0 / 100 in 5 min. The product was desalted with a Sep-Pak C18 cartridge and cation-exchange resin, affording the product (2,8 mg, 0.8 pmol, y. 0.6% in 3 steps as a sodium salt).NMR (400 MHz, CD3OD): 3 11 .64 (s, 2H), 10.59 (s, 4H), 10.30 (s, 4H), 10.28 (s, 4H), 9.07 (d, J - 8.1 Hz, 4H), 8.85-8.81 (m, 8H), 8.04-7.96 (m, 8H), 2.61- 2.53 (m. 48H), 2.04-2.00 (m, 8H). 1.53-1 ,45 (m, 24H), -0.57—0.63 (m, 8H), -1.77—1.81 (m, 8H), -2.36 (s, 24H). HRMS (ESI”) m / z: calcd for CissHissNsoNa^oS^Sia: 844.6455 [M-4Na]4": found: 844.6400.Example 24

[0518] in this example, compound p-Tz IR700C10SE was conjugated to cetuximab, an antibody for EGFR, to obtain an antibody-compound conjugate, / n vitro PIT was then performed with this antibody-compound conjugate using A431 cells.

[0519] A431 cells were incubated in DMEM on a 3.5 cm glass bottom dish Next day, cells were washed with DMEM phenol red (-) and incubated with 5 ug / mL (final) p-TzIR700C10SE or IR700 in DMEM phenol red (■) for 1 hour at 37 °C. Then, cells were washed with DMEM phenol red (-) and set on an upright microscope. Cells were irradiated with 690 nm LED light for 5 minutes (0.026 W / cm2, 7.8 J / cm2) and microscopic images were taken (see FIG. 2) after 5 minutes, 15 minutes, and 30 minutes. As can be seen by the results in4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025FIG. 2, particularly the zoomed images in the bottom row, blebs were formed to induce cell death using the bicmoiecule-compound conjugate within 5...

Claims

1. 4239-111829-02 09 / 03 / 25 E- t37-2G24-*>POGt FILED ELECTRONICALLY ON SEPTEMBER 3, 2025We claim:1 . A compound having a structure according to Formula I or Formula IIFormula II wherein:X is a biomolecule-binding moiety or a precursor thereto; the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p[O(CR2)tJq-{X}, wherein{Core; represents attachment to the phthalocyanine core and {X} represents attachment to X; each R, independently for each occurrence, is selected from hydrogen, halogen, aliphatic, heteroaliphatic, or aromatic;Y is selected from (i) a functional group produced from a reaction between two clickable functional groups; (ii) -CH=CH-[Q1]S-, wherein s is 1 or 0 and Q1is selected from aromatic, -C(=O)Y’-, or -S(=O)2Y’, wherein Y’ is NR” or O, wherein4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025R” is H, -GN, CF3, or a sulfonyl group; or (iii) -C^C-Q2wherein Q2is - (CH2)UC(=O)Y’-, wherein u is an integer selected from 1 to 10, Y’ is NR” or O, wherein R” is H, -CN, CF3, or a sulfonyl group;Z is a heteroatom; m is 1 or 0; each of n, p, and t independently is selected from an integer ranging from 0 to 50; and q is an integer selected from 0 to 50;G, if present, is selected from halogen or Linker-X, wherein the linker group and the X group are as defined above; each of Ria, R2a, R3a, R1b, R2b, and R3bindependently is selected from hydrogen, aliphatic, halogen, heteroaliphatic, aromatic, thiol, hydroxyl, or amine; or(I) R1aand R1bjoin together, with the carbon atoms to which they are attached, to form a 6-membered aromatic ring,(ii) R2aand R2bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring,(iii) R3aand R3bjoin together, with the carbon atoms to which they are attached, to form a six-membered aromatic ring, or(iv) any combination of two or more of (i)-(iii); andL is selected from -(CHs),--, -Si(R5)2(CH2)r-, -C(=O)(CH2)r, or -PhfCHs)-, wherein each R5independently is aliphatic or aryl, r is an integer selected from 1 to 5 and wherein any CH2group of the L group is attached to the quaternary amine of Formula I or Formula II.

2. The compound of claim 1 , wherein the compound has a structure according to Formula IA or Formula IBFormula IA4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IB.

3. The compound of claim 1 or claim 2, wherein the compound has a structure according to Formula IA(i) - Formula I A(iv)Formula IA(li)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IA(lv) wherein ring A is a ring system selected from a phenyl ring, a pyridyl ring, a triazole, a cycloocta[d|pyridazine, a cycloocta[d|triazolesor a triazole-funciionalized DBCO.

4. The compound of any one of claims 1-3, wherein the compound has a structure according to one of Formulas IA(i)(a), IA(i)(b), IA(l)(c), IA(i)(d), I A(i)(e), IA(i)(f), I A(i)(g), I A(i)(h), or IA(i)(i)Formula !A(i)(a)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IA(i)(d)Formula I A(l)(e)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20255. The compound of claim 1 , wherein the compound has a structure according to Formula I B(i) or Formula IB(ii)Formula IB(H) wherein ring A is a ring system selected from a phenyl ring, a triazole, a cycloocta[djpyridazine, a cyclooctafr^triazole, or a trlazole-functionalized DBCO.

6. The compound according to claim 1 or claim 5, wherein the compound has a structure according io one of Formulas IB(i)(a), IB(i)(b), IB(i)(c), or IB(i)(d)Formula IB(l)(a)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IB(s)(d).

7. The compound according to any one of claims 1-6, wherein G is present and is selected from chloro, bromo, fluoro, iodo, or Linker-X, wherein the linker and X groups of Linker-X are as defined for claim 1 .

8. The compound according to any one of claims 1-7, wherein G is positioned ortho io the Linker-X group of Formula I.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20259. The compound according to any one of claims 1 -8, wherein L is -(CH2)4, -Si(Me)2(CH2)3-Si(Et)2(CH2)3-, -Si( / Pr)2(CH2)3-, or -Si(Ph)2(CH2)3-.

10. The compound according to claim 1 , wherein the compound has a structure according to Formula HA, Formula IIB, or Formula IICFormula IIB4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula liC wherein ring A is a ring system selected from a phenyl ring, a triazole, a cycloocta[a]pyridazine, a cyclooctafc^triazole, or a triazole-functionaiized DBCO.1 1 , The compound according to claim 1 or claim 10, wherein the compound has a structure according to one of Formulas ll(A)(i), IIA(ii), IIB(i), IIB(ii), IIC(i), HC(ii), I IC(iii), or IIC(iv)Formula IIA(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula ilB(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula iSC(i)4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IIC(iv).4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 202512. The compound of any one of claims 1 -1 1 , wherein X is a biomolecule-binding moiety comprising an activated ester group.

13. The compound of claim 12, wherein the activated ester is an NHS ester.

14. The compound of any one of claims 1 -1 1 , wherein X is a biomolecule-binding moiety precursor.

15. The compound of claim 14, wherein the biomolecule-binding moiety precursor is a carboxylic acid or a carboxylate.

16. The compound of any one of claims 1 -1 1 , wherein X is a clickable functional group configured to react with a separate clickable functional group present on a bacteria- speciflc protein.

17. The compound of claim 16, wherein the clickable functional group is an alkyne or an azide.

18. The compound of any one of claims 1 or 2, wherein Y comprises a ring formed between (i) an alkyne and an azide; (ii) a tetrazine and a trans-cyclooctene; (ill) an azide and a dibenzocyclooctyne (DBCO); or (iv) an azide and a bicyclo[6.1.0]nonyne.

19. The compound of any one of claims 1 , 2, or 18, wherein Y comprises a ring formed between an alkyne and an azide.

20. The compound of claim 19, wherein the ring formed between the alkyne and the azide is a triazole.21 . The compound of any one of claims 1 , 2, or 12-17, wherein m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR?)p-{X} or {Core}-(CR2)n-Y- (CR2)p[O(CRz)t]q-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , t is 2, q is an integer selected from 1 to 6, and Y is a 1 ,2,3- triazole.

22. The compound of any one of claims 1 , 2, or 12-17, wherein m is 1 and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p-{X}, wherein each4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , Y is -CH-CH-Ph- or -CH-CH-Pyridyl-, and m is 0.

23. The compound of any one of claims 1 , 2, or 12-17, wherein m is 1 and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(Z)m-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , Y is -CH-CH-Ph- or -CH=CH-Pyridyl-, Z is O, and m is 1 .

24. The compound of any one of claims 1 , 2, or 12-17, wherein m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3. p is an integer selected from zero to 21 , and wherein ’ wherein Y’ is O or -NH, -N(CN), -NCF3, -NSO2M25. The compound of any one of claims 1 , 2, or 12-17, wherein m is zero and the Linker has a structure according to a formula {Core}-(CR2)n-Y-(CR2)p-{X}, wherein each R is H, n is an integer selected from 0, 1 , 2, or 3, p is an integer selected from zero to 21 , and wherein Y is -C^C(CH2)2C(=O)NH-(CH2)r, wherein t is an integer selected from 1 to 10.

26. The compound of any one of claims 1 , 2, or 12-17, wherein each of n and m is zero and the Linker has a structure according to -CH=CH-(CR2)P-, -CH==CH-C(O)O-(CR2)P, or -CH=CH-C(O)NR"-(CR2)P-.

27. The compound of any one of claims 1 -4 or 12-20, wherein the compound isFILED ELECTRONICALLY ON SEPTEMBER 3, 202528. The compound of any one of claims 1-4, 12-15, 19-26, wherein the compoundted from4239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 20254239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025; or4239-111829-02 08 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 202529. The compound of any one of claims 1-26 or 28, wherein the compound is conjugated to a biomolecule through the X group.

30. A conjugate formed by coupling a biomolecule with a compound according to any one of claims 1 -26 or 28, wherein the biomolecule becomes bound to the compound upon reaction between a functional group of the biomolecule and the X group of the compound.31 . The conjugate of claim 30, wherein the biomolecule is an antibody.

32. The conjugate of claim 30, wherein antibody is a humanized antibody that specifically binds to a surface protein on a cancer cell.

33. A method for treating a subject or sample using NIR-PIT, the method comprising: administering a compound according to any one of claims 1-4, 16-20, or 27, or a conjugate according to any one of claims 30-32, or a pharmaceutically acceptable composition thereof, to the subject or the sample: and irradiating the conjugate by application of light to a targeted portion of the subject or the sample.4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 202534. The method of claim 33, wherein the light is applied (i) in a quantity sufficient to produce fluorescence of the conjugate, (ii) in a quantity sufficient to induce killing of a target or a target cell present in the subject or the sample, or a combination of (I) and (ii).

35. The method of claim 33 or claim 34, wherein the light is light of a wavelength ranging from 650 nm to 1100 nm.

36. The method of any one of claims 33-35, wherein the light is applied at a dose of at least 1 J / cm2.

37. The method of any one of claims 33-36, wherein administering is carried out using intravenous administration.

38. The method of any one of claims 33-36, wherein the biomolecule of the conjugate is an antibody.

39. The method of any one of claims 33-38, wherein the subject or the sample comprises a cell comprising a surface protein selected from a tumor-specific protein or an immune cell-specific protein.

40. The method of any one of claims 33-39, wherein the subject or the sample comprises a bacterial species.41 . A method of making a compound according to any one of claims 1-28, comprising: converting a phthalocyanine core precursor having a structure according to Formula III to the compound by performing a click chemistry reaction or a palladium-catalyzed carbon-carbon cross coupling reaction; wherein Formula III is4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula III; andR4is selected from halogen or a group having a structure according to a formula {Core}- (GRaJn-CFG, wherein CFG is a clickable functional group and “{Core}” represents attachment of R':to the phthalocyanine core precursor.42, The method of claim 41 , wherein the phthalocyanine core precursor has a structure according to Formula IIIA, 11 IB, or IIICFormula IIIB4239-111829-02 09 / 03 / 25 FILED ELECTRONICALLY ON SEPTEMBER 3, 2025Formula IHC.

43. The method of claim 41 or 42, wherein the click chemistry reaction comprises a copper- catalyzed azide-alkyne cycloaddition.

44. The method of claim 41 or 42, wherein the palladium-catalyzed carboncarbon cross coupling is a Heck reaction or a Sonogashira reaction.

Images