Radionuclide compositions for the detection of tumor cells and methods of use thereof

Abstract

The present invention relates to a compound having the structure: [Formula 1] The present invention provides a compound having the formula TIFF2025530298000209.tif51170, or a salt or ester thereof.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 62 / 481,517, filed January 25, 2023, and U.S. Provisional Patent Application No. 63 / 375,159, filed September 9, 2022, the entire contents of which are incorporated herein by reference.

[0002] Throughout this application, various publications are referenced, including those referenced within parentheses. The disclosures of all publications mentioned in this application are incorporated by reference in their entireties to provide further description of the art to which this invention pertains and features in that art that may be used in conjunction with the present invention.

[0003] [STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT] This invention was made with government support under Grant No. EB027982 awarded by the National Institutes of Health. The government has certain rights in this invention. [Background technology]

[0004] Pretargeting positron emission tomography (PET) provides quantitative, non-invasive, whole-body in vivo profiling of macromolecules with an overall lower whole-body radiation dose compared to directly radiolabeled macromolecules (Non-Patent Documents 1 and 2). Pretargeting is a two-step strategy that involves the administration of a target-bound macromolecule, which accumulates at the target site over several days while the unbound macromolecule is excreted from non-target tissues. In the second step, a bioorthogonal small molecule radioligand is administered (Figure 1). Due to the low molecular weight of the radioligand, its accumulation and excretion from the target occur more rapidly than the initial macromolecule. The present invention utilizes host-guest complexation as a specific pretargeting interaction between the macromolecule and the radioligand. The selected host-guest pair, cucurbit[7]uril-adamantane (CB7-Adma, K a about 10 14 M -1) have been hypothesized to make an ideal interaction pair for pretargeting PET due to their high in vivo stability, modularity, and low immunogenicity (Non-Patent Documents 3, 4, and 5). When an Adma guest bearing adjacent positively charged moieties binds to the carbonyl framework cavity of a macrocyclic CB7 host molecule through multiple van der Waals and ion-dipole interactions, a strong complex is formed between the two molecules. To date, medical imaging applications utilizing host-guest chemistry have been limited to preformed host-guest complexes to enhance the stability and / or sensitivity of the imaging agent (Non-Patent Documents 6, 7, and 8). In nuclear medicine, high-affinity non-covalent binding between CB7 and Adma molecules has remained minimally explored (Non-Patent Document 9).

[0005] Three copper-64-labeled Adma guest molecules [ 64 Cu]Cu-NOTA-Adma(1), [ 64 Cu]Cu-NOTA-PEG3-Adma(2) and [ 64 [Cu]Cu-NOTA-PEG7-Adma (3) was synthesized and characterized (Figure 2A). The in vivo profile of the pretargeting ligand was evaluated using a CB7-modified carcinoembryonic antigen (CEA)-targeting humanized full-length antibody (CB7-M5A) as a secondary pretargeting agent. To explore the potential of this platform, two pretargeting time lag schedules, 72 and 144 hours, were investigated. Pretargeting studies were performed in BxPC3 (CEA+) and MIAPaCa-2 (CEA-) human pancreatic cancer mouse xenografts (Non-Patent Documents 10, 11, and 12).

[0006] The biodistribution and dosimetry of the pretargeting Adma radioligand were compared with that of directly Zr-89-labeled M5A. The high stability, mutual affinity, and human compatibility of the proposed CB7-Adma pretargeting agent provide an excellent basis for a broadly applicable pretargeting platform. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Altai, 2017 [Non-patent document 2] Jallinoja, 2021 [Non-patent document 3] Assaf K.I., 2015 [Non-patent document 4] Shetty D, 2015 [Non-patent document 5] Wanka L, 2013 [Non-patent document 6] Zhao, 2022 [Non-Patent Document 7] Sembo-Backonly, 2021 [Non-patent document 8] Wu 2021 [Non-Patent Document 9] Strebl MG, 2018 [Non-Patent Document 10] Girgis 2011 [Non-Patent Document 11] Yunis 1977 [Non-Patent Document 12] Tan 1986 Summary of the Invention

[0008] The present invention relates to a compound having the structure: [ka]

[0009] (wherein Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N( alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH), wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0010] The present invention relates to a compound having the structure: [ka]

[0011] (wherein Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H), alkyl-N (alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4), alkyl-N(alkylaryl-OH)2, alkyl-N(alkylheteroaryl-OH)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO2H), alkyl-P(O)(OH)2, alkylaryl-P(O)(OH)2 or alkylheteroaryl-P(O)(OH)2; wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0012] The present invention relates to a compound having the structure: [ka]

[0013] (wherein Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H), alkyl-N (alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4), alkyl-N(alkylaryl-OH)2, alkyl-N(alkylheteroaryl-OH)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO2H), alkyl-P(O)(OH)2, alkylaryl-P(O)(OH)2 or alkylheteroaryl-P(O)(OH)2; wherein R4 is independently at each occurrence -H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof. [Brief explanation of the drawings]

[0014] [Figure 1A] FIG. 1 shows a two-step cucurbit[7]uril-adamantane pretargeting approach. [Figure 1B] FIG. 1 shows a two-step cucurbit[7]uril-adamantane pretargeting approach. [Figure 2] (A) Chemical structures of [64Cu]Cu-NOTA-Adma (1), [64Cu]Cu-NOTA-PEG3-Adma (2), and [64Cu]Cu-NOTA-PEG7-Adma (3), as well as their respective partition coefficients (log D) and blood half-lives. (B) In vitro stability and plasma protein binding of 1–3 in phosphate-buffered saline (PBS pH=7.4) and bovine plasma at 37 °C. [Figure 3] Figure 1 shows the in vivo biodistribution of pretargeted [64Cu]Cu-NOTA-Adma;1, [64Cu]Cu-NOTA-PEG3-Adma;2, and [64Cu]Cu-NOTA-PEG7-Adma;3 in nude mice bearing BxPC3 tumors. %ID / g; percentage of injected dose; ns; not significant; *p<0.05. [Figure 4]Maximum intensity projection PET images of pretargeted [64Cu]Cu-NOTA-Adma;1, [64Cu]Cu-NOTA-PEG3-Adma;2, and [64Cu]Cu-NOTA-PEG7-Adma;3 in BxPC3 tumor-bearing nude mice 4, 8, and 24 hours after radioligand injection on a 72-hour time-lag pretargeting schedule. The location of the tumor on the right shoulder is highlighted by a red circle. [Figure 5] Figure 1 shows the in vivo profiles of [89Zr]Zr-DFO-M5A 72 hours after injection and pretargeting 2 24 hours after injection in female nude mice bearing BxPC3 and MIAPaCa-2 tumors. Maximum intensity projection PET images of [89Zr]Zr-DFO-M5A (A) and pretargeting 2 (B), as well as the in vivo biodistribution of [89Zr]Zr-DFO-M5A (C) and pretargeting 2 (D). Mice treated with 2 were injected with CB7-M5A 72 hours prior. The location of the tumor on the right shoulder is highlighted by a red circle. [Figure 6] FIG. 1 shows the reaction scheme for the synthesis of 4 and 5. I. Triethylamine, methanol; II. Sodium triacetoxyborohydride; III. Iodomethane, sodium hydroxide; IV. Trifluoroacetic acid, dichloromethane; Vp-SCN-Bn-NOTAx3HCl, N,N-diisopropylethylamine and dimethyl sulfoxide. [Figure 7] FIG. 1 shows the reaction scheme for the synthesis of 6 and 7. I. Triethylamine, methanol; II. Sodium triacetoxyborohydride; III. Iodomethane, sodium hydroxide, triethylamine; IV. Trifluoroacetic acid, dichloromethane; Vp-SCN-Bn-NOTAx3HCl, N,N-diisopropylethylamine, dimethyl sulfoxide. [Figure 8]FIG. 1 shows a reaction scheme for the synthesis of 8 and 9. I. Triethylamine, methanol; II. Sodium triacetoxyborohydride; III. Iodomethane, sodium hydroxide; IV. Trifluoroacetic acid, dichloromethane; Vp-SCN-Bn-NOTAx3HCl, N,N-diisopropylethylamine, dimethyl sulfoxide. [Figure 9] UV-Vis HPLC chromatograph of NOTA-Adma (5) monitoring absorbance at 254 nm. [Figure 10] UV-Vis HPLC chromatograph of NOTA-PEG3-Adma (7) monitoring absorbance at 254 nm. [Figure 11] UV-Vis HPLC chromatograph of NOTA-PEG7-Adma (9) monitoring absorbance at 254 nm. [Figure 12] Radio-HPLC chromatograph of [64Cu]Cu-NOTA-Adma (1). [Figure 13] 1 shows the radio-HPLC chromatograph of [64Cu]Cu-NOTA-PEG3-Adma (2). [Figure 14] 1 shows the radio-HPLC chromatograph of [64Cu]Cu-NOTA-PEG7-Adma (3). [Figure 15] FPLC chromatographs of unmodified M5A (A), CB7-M5A (B) and DFO-M5A (C) with absorbance detection at 280 nm. [Figure 16] FIG. 1 shows the percentage of internalized and membrane-bound [64Cu]CuCl2 and [64Cu]Cu-NOTA-PEG3-Adma(2) relative to the total added activity over 6 hours in BxPC3 cells. [Figure 17] Figure 1 shows biphasic decay curves based on %ID / g of blood samples as a function of time for [Cu]Cu-NOTA-Adma (A), [Cu]Cu-NOTA-PEG3-Adma (B), and [Cu]Cu-NOTA-PEG7-Adma (C). [Figure 18]Figure 1 shows Western blotting of carcinoembryonic antigen (CEA) in BxPC3 and MIAPaCa-2 cell lysates, using two CEA-targeting antibodies, hT84.66-M5A and H.426.3. [Figure 19] Maximum intensity projection PET images of pretargeted [64Cu]Cu-NOTA-PEG3-Adma;2 in nude mice bearing BxPC3 tumors 4, 8, and 24 hours after radioligand injection. Mice were administered CB7-M5A 144 hours before radioligand injection. The location of the tumor on the right shoulder is highlighted by a red circle. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention relates to a compound having the structure:

[0016] [ka]

[0017] (wherein Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N( alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH), wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, or tetramethylenedisulfotetramine), or a salt or ester thereof.

[0018] The present invention relates to a compound having the structure:

[0019] [ka]

[0020] (wherein Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H), alkyl-N (alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4), alkyl-N(alkylaryl-OH)2, alkyl-N(alkylheteroaryl-OH)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO2H), alkyl-P(O)(OH)2, alkylaryl-P(O)(OH)2 or alkylheteroaryl-P(O)(OH)2; wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0021] The present invention relates to a compound having the structure:

[0022] [ka]

[0023] (wherein Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N( alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH), wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, or tetramethylenedisulfotetramine), or a salt or ester thereof.

[0024] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0025] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0026] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0027] In some embodiments, n and m are each independently 1, 2, or 3.

[0028] In some embodiments, n and m are each independently 1.

[0029] In some embodiments, n is 1, 2, or 3.

[0030] In some embodiments, m is 1, 2, or 3.

[0031] In some embodiments, n is 1 or 2.

[0032] In some embodiments, m is 1 or 2.

[0033] In some embodiments, n is 1.

[0034] In some embodiments, m is 1.

[0035] In some embodiments, n and m are the same.

[0036] In some embodiments, n and m are different.

[0037] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0038] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0039] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0040] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0041] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0042] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0043] In some embodiments, R1 and R2 are methyl.

[0044] In some embodiments, R1 and R2 are ethyl.

[0045] In some embodiments, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, or an alkenyl-heteroaryl-thiourea.

[0046] In some embodiments, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, or an alkyl-cycloalkyl-thiourea.

[0047] In some embodiments, X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea.

[0048] In some embodiments, X is an alkyl-aryl-thiourea.

[0049] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0050] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0051] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0052] In some embodiments, the chemical linker L is PEG.

[0053] In some embodiments, the chemical linker L has the following structure: [ka]

[0054] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0055] In some embodiments of the chemical linker L, m is 1, 2, 3, 4, 5, 6, or 7.

[0056] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0057] In some embodiments of the chemical linker, L, m is 3.

[0058] In some embodiments, the chemical linker L has the following structure: [ka]

[0059] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0060] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0061] In some embodiments of the chemical linker, L, m is 3.

[0062] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0063] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0064] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0065] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0066] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0067] In some embodiments, R4 is -OH.

[0068] In some embodiments, R4 is -NH2.

[0069] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0070] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0071] In some embodiments, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0072] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[0073] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[0074] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[0075] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[0076] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[0077] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[0078] In some embodiments, at least two of Y1, Y2, Y3, and Y4 are the same.

[0079] In some embodiments, at least three of Y1, Y2, Y3, and Y4 are the same.

[0080] In some embodiments, Y1, Y2, Y3, and Y4 are the same.

[0081] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0082] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0083] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0084] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0085] In some embodiments, Y 1 , Y 2 , and Y 3 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0086] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2H.

[0087] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2NH2.

[0088] In some embodiments, at least one of Y 1 , Y 2 , and Y 3 is alkyl-N(alkyl-CO 2 H) 2 .

[0089] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-CO2H.

[0090] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-CO2NH2.

[0091] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-N(alkyl-CO2H)2.

[0092] In some embodiments, at least two of Y1, Y2, and Y3 are the same.

[0093] In some embodiments, Y1, Y2 and Y3 are the same.

[0094] In some embodiments, at least one of Y 1 , Y 2 , and Y 3 is H.

[0095] In some embodiments, none of Y 1 , Y 2 and Y 3 is H.

[0096] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0097] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0098] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0099] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0100] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] or is.

[0101] In some embodiments, Y and Y are [ka] and Y2 and / or Y4 are [ka] is.

[0102] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0103] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0104] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0105] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0106] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0107] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0108] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0109] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0110] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0111] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0112] In some embodiments, the guest molecule A is a substituted adamantane.

[0113] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0114] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0115] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0116] In some embodiments, the guest molecule A is a substituted diamantane.

[0117] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0118] In some embodiments, guest molecule A is a substituted ferrocene.

[0119] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0120] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0121] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0122] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0123] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0124] In some embodiments, the present invention provides a compound having the structure: [ka]

[0125] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0126] In some embodiments, the present invention provides a compound having the structure: [ka]

[0127] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0128] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0129] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0130] In some embodiments, the compound is [ka] It's surprising.

[0131] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0132] In some embodiments, n and m are each independently 1, 2, or 3.

[0133] In some embodiments, n and m are 1.

[0134] In some embodiments, n is 1, 2, or 3.

[0135] In some embodiments, m is 1, 2, or 3.

[0136] In some embodiments, n is 1 or 2.

[0137] In some embodiments, m is 1 or 2.

[0138] In some embodiments, n is 1.

[0139] In some embodiments, m is 1.

[0140] In some embodiments, n and m are the same.

[0141] In some embodiments, n and m are different.

[0142] In some embodiments, o is 0, 1, 2, 3, 4, 5, or 6.

[0143] In some embodiments, o is 0, 1, 2, or 3.

[0144] In some embodiments, o is 1 or 2.

[0145] In some embodiments, o is 1.

[0146] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0147] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0148] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0149] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0150] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0151] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0152] In some embodiments, R1 and R2 are methyl.

[0153] In some embodiments, R1 and R2 are ethyl.

[0154] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0155] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0156] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0157] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0158] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0159] In some embodiments, R4 is -OH.

[0160] In some embodiments, R4 is -NH2.

[0161] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0162] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0163] In some embodiments, Y 1 , Y 2 , and Y 3 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0164] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2H.

[0165] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2NH2.

[0166] In some embodiments, at least one of Y 1 , Y 2 , and Y 3 is alkyl-N(alkyl-CO 2 H) 2 .

[0167] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-CO2H.

[0168] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-CO2NH2.

[0169] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-N(alkyl-CO2H)2.

[0170] In some embodiments, at least two of Y1, Y2, and Y3 are the same.

[0171] In some embodiments, Y1, Y2 and Y3 are the same.

[0172] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0173] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0174] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0175] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0176] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0177] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0178] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0179] In some embodiments, Y and Y are [ka] and Y2 and / or Y4 are [ka] is.

[0180] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0181] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0182] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0183] In some embodiments, the chemical linker L is PEG.

[0184] In some embodiments, the chemical linker L has the following structure: [ka]

[0185] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0186] In some embodiments, the chemical linker L has the following structure: [ka]

[0187] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0188] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0189] In some embodiments of the chemical linker, L, m is 3.

[0190] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0191] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0192] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0193] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0194] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0195] In some embodiments, R4 is -OH.

[0196] In some embodiments, R4 is -NH2.

[0197] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0198] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0199] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0200] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0201] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0202] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0203] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0204] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0205] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0206] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0207] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0208] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0209] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0210] In some embodiments, the guest molecule A is a substituted adamantane.

[0211] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0212] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0213] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0214] In some embodiments, the guest molecule A is a substituted diamantane.

[0215] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0216] In some embodiments, guest molecule A is a substituted ferrocene.

[0217] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0218] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0219] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0220] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0221] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0222] In some embodiments, the present invention provides a compound having the structure: [ka]

[0223] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl-CO2H), alkyl-N(aryl- alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0224] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0225] In some embodiments, n and m are each independently 1, 2, or 3.

[0226] In some embodiments, n and m are 1.

[0227] In some embodiments, n is 1, 2, or 3.

[0228] In some embodiments, m is 1, 2, or 3.

[0229] In some embodiments, n is 1 or 2.

[0230] In some embodiments, m is 1 or 2.

[0231] In some embodiments, n is 1.

[0232] In some embodiments, m is 1.

[0233] In some embodiments, n and m are the same.

[0234] In some embodiments, n and m are different.

[0235] In some embodiments, o is 0, 1, 2, 3, 4, 5, or 6.

[0236] In some embodiments, o is 0, 1, 2, or 3.

[0237] In some embodiments, o is 1 or 2.

[0238] In some embodiments, o is 1.

[0239] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0240] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0241] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0242] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0243] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0244] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0245] In some embodiments, R1 and R2 are methyl.

[0246] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0247] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0248] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0249] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0250] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0251] In some embodiments, R4 is -OH.

[0252] In some embodiments, R4 is -NH2.

[0253] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0254] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0255] In some embodiments, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0256] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[0257] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[0258] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[0259] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[0260] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[0261] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[0262] In some embodiments, at least two of Y1, Y2, and Y3, Y4 are the same.

[0263] In some embodiments, at least three of Y1, Y2, Y3, and Y4 are the same.

[0264] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0265] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0266] In some embodiments, Y1, Y2, Y3, and Y4 are the same.

[0267] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0268] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0269] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0270] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0271] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0272] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0273] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0274] In some embodiments, Y and Y are [ka] and Y2 and / or Y4 are [ka] is.

[0275] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0276] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0277] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0278] In some embodiments, the chemical linker L is PEG.

[0279] In some embodiments, the chemical linker L has the following structure: [ka]

[0280] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0281] In some embodiments, the chemical linker L has the following structure: [ka]

[0282] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0283] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0284] In some embodiments of the chemical linker, L, m is 3.

[0285] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0286] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0287] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0288] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0289] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0290] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0291] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0292] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0293] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0294] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0295] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0296] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0297] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0298] In some embodiments, the guest molecule A is a substituted adamantane.

[0299] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0300] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0301] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0302] In some embodiments, the guest molecule A is a substituted diamantane.

[0303] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0304] In some embodiments, guest molecule A is a substituted ferrocene.

[0305] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0306] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0307] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0308] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0309] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0310] The present invention relates to a compound having the structure: [ka]

[0311] wherein L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; preferably, R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH2.

[0312] The present invention relates to a compound having the structure: [ka]

[0313] wherein L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; preferably, R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH2.

[0314] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0315] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0316] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0317] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0318] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0319] In some embodiments, R4 is -OH.

[0320] In some embodiments, R4 is -NH2.

[0321] In some embodiments, the compound is [ka] It's surprising.

[0322] The present invention relates to a compound having the structure: [ka]

[0323] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0324] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0325] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0326] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0327] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0328] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0329] In some embodiments, R4 is -OH.

[0330] In some embodiments, R4 is -NH2.

[0331] The present invention relates to a compound having the structure: [ka]

[0332] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0333] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0334] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0335] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0336] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0337] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0338] In some embodiments, R4 is -OH.

[0339] In some embodiments, R4 is -NH2.

[0340] The present invention relates to a compound having the structure: [ka]

[0341] wherein L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; preferably, R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH2.

[0342] The present invention relates to a compound having the structure: [ka]

[0343] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0344] The present invention relates to a compound having the structure: [ka]

[0345] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0346] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0347] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0348] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0349] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0350] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0351] In some embodiments, R4 is -OH.

[0352] In some embodiments, R4 is -NH2.

[0353] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0354] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0355] The present invention relates to a compound having the structure:

[0356] [ka]

[0357] wherein L is alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, or polyethylene glycol (PEG); n and m are each independently 0, 1, 2, or 3; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, or 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; R4, at each occurrence, is independently -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0358] In some embodiments, the compound is [ka] It's surprising.

[0359] The present invention relates to a compound having the structure: [ka]

[0360] wherein L is alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, or polyethylene glycol (PEG); n and m are each independently 0, 1, 2, or 3; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, or 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; R4, independently in each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; preferably, R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH2.

[0361] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0362] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0363] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0364] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0365] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0366] In some embodiments, R4 is -OH.

[0367] In some embodiments, R4 is -NH2.

[0368] In some embodiments, n and m are each independently 1, 2, or 3.

[0369] In some embodiments, n and m are 1.

[0370] In some embodiments, n is 1, 2, or 3.

[0371] In some embodiments, m is 1, 2, or 3.

[0372] In some embodiments, n is 1 or 2.

[0373] In some embodiments, m is 1 or 2.

[0374] In some embodiments, n is 1.

[0375] In some embodiments, m is 1.

[0376] In some embodiments, n and m are the same.

[0377] In some embodiments, n and m are different.

[0378] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0379] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0380] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0381] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0382] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0383] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0384] In some embodiments, R1 and R2 are methyl.

[0385] In some embodiments, alkyl is C 1~6 It is alkyl.

[0386] In some embodiments, alkyl is C 1~3 It is alkyl.

[0387] In some embodiments, the alkyl is methyl.

[0388] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[0389] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.

[0390] In some embodiments, the aryl is phenyl.

[0391] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0392] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0393] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0394] In some embodiments, the chemical linker L is PEG.

[0395] In some embodiments, the chemical linker L has the following structure: [ka]

[0396] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0397] In some embodiments, the chemical linker L has the following structure: [ka]

[0398] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0399] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0400] In some embodiments of the chemical linker, L, m is 3.

[0401] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0402] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0403] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0404] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0405] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0406] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0407] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), or -N-(alkyl).

[0408] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0409] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0410] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0411] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0412] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0413] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0414] In some embodiments, the guest molecule A is a substituted adamantane.

[0415] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0416] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0417] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0418] In some embodiments, the guest molecule A is a substituted diamantane.

[0419] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0420] In some embodiments, guest molecule A is a substituted ferrocene.

[0421] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0422] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), or —NH—(C1-C6 alkyl).

[0423] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl or -alkyl-N-(C1-C6 alkyl).

[0424] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0425] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0426] The present invention relates to a compound having the structure: [ka]

[0427] wherein L is alkyl, alkenyl, alkynyl, alkyl ether, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH.

[0428] In some embodiments, the compound is [ka] It's surprising.

[0429] The present invention relates to a compound having the structure: [ka]

[0430] wherein L is alkyl, alkenyl, alkynyl, alkyl ether, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH.

[0431] In some embodiments, n and m are each independently 1, 2, or 3.

[0432] In some embodiments, n and m are 1.

[0433] In some embodiments, n is 1, 2, or 3.

[0434] In some embodiments, m is 1, 2, or 3.

[0435] In some embodiments, n is 1 or 2.

[0436] In some embodiments, m is 1 or 2.

[0437] In some embodiments, n is 1.

[0438] In some embodiments, m is 1.

[0439] In some embodiments, n and m are the same.

[0440] In some embodiments, n and m are different.

[0441] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0442] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0443] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0444] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0445] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0446] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0447] In some embodiments, R1 and R2 are methyl.

[0448] In some embodiments, R1 and R2 are ethyl.

[0449] The present invention relates to a compound having the structure: [ka] The present invention provides a compound having the formula:

[0450] The present invention provides a metal complex comprising a compound according to the present invention, wherein the compound is coordinated to a metal.

[0451] The present invention relates to a compound having the structure: [ka]

[0452] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0453] The present invention relates to a compound having the structure: [ka]

[0454] (wherein M is a metal, Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl-CO2H), alkyl-N(aryl- alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0455] The present invention relates to a compound having the structure: [ka]

[0456] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0457] In some embodiments, the metal complex is [ka] It's surprising.

[0458] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0459] In some embodiments, n and m are each independently 1, 2, or 3.

[0460] In some embodiments, n and m are 1.

[0461] In some embodiments, n is 1, 2, or 3.

[0462] In some embodiments, m is 1, 2, or 3.

[0463] In some embodiments, n is 1 or 2.

[0464] In some embodiments, m is 1 or 2.

[0465] In some embodiments, n is 1.

[0466] In some embodiments, m is 1.

[0467] In some embodiments, n and m are the same.

[0468] In some embodiments, n and m are different.

[0469] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0470] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0471] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0472] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0473] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0474] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0475] In some embodiments, R1 and R2 are methyl.

[0476] In some embodiments, R1 and R2 are ethyl.

[0477] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0478] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0479] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0480] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0481] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0482] In some embodiments, R4 is -OH.

[0483] In some embodiments, R4 is -NH2.

[0484] In some embodiments, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, or an alkenyl-heteroaryl-thiourea.

[0485] In some embodiments, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, or an alkyl-cycloalkyl-thiourea.

[0486] In some embodiments, X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea.

[0487] In some embodiments, X is an alkyl-aryl-thiourea.

[0488] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0489] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0490] In some embodiments, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0491] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[0492] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[0493] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[0494] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[0495] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[0496] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[0497] In some embodiments, at least two of Y1, Y2 and Y3, Y4 are the same.

[0498] In some embodiments, at least three of Y1, Y2, Y3, and Y4 are the same.

[0499] In some embodiments, Y1, Y2, Y3 and Y4 are the same.

[0500] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0501] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0502] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0503] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0504] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0505] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0506] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0507] In some embodiments, Y and Y are [ka] and Y2 and / or Y4 are [ka] is.

[0508] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0509] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0510] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0511] In some embodiments, the chemical linker L is PEG.

[0512] In some embodiments, the chemical linker L has the following structure: [ka]

[0513] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0514] In some embodiments, the chemical linker L has the following structure: [ka]

[0515] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0516] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0517] In some embodiments of the chemical linker, L, m is 3.

[0518] In some embodiments, the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0519] In some embodiments, the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0520] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0521] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0522] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0523] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0524] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0525] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0526] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0527] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0528] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0529] In some embodiments, the guest molecule A is a substituted adamantane.

[0530] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0531] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0532] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0533] In some embodiments, the guest molecule A is a substituted diamantane.

[0534] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0535] In some embodiments, guest molecule A is a substituted ferrocene.

[0536] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0537] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0538] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0539] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0540] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0541] In some embodiments, the present invention provides a compound having the structure: [ka]

[0542] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; o is 0, 1, 2, 3, 4, 5 or 6; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0543] In some embodiments, the present invention provides a compound having the structure: [ka]

[0544] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; o is 0, 1, 2, 3, 4, 5 or 6; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0545] In some embodiments, the metal complex is [ka] It's surprising.

[0546] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0547] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0548] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0549] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0550] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0551] In some embodiments, R4 is -OH.

[0552] In some embodiments, R4 is -NH2.

[0553] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0554] In some embodiments, n and m are each independently 1, 2, or 3.

[0555] In some embodiments, n and m are 1.

[0556] In some embodiments, n is 1, 2, or 3.

[0557] In some embodiments, m is 1, 2, or 3.

[0558] In some embodiments, n is 1 or 2.

[0559] In some embodiments, m is 1 or 2.

[0560] In some embodiments, n is 1.

[0561] In some embodiments, m is 1.

[0562] In some embodiments, n and m are the same.

[0563] In some embodiments, n and m are different.

[0564] In some embodiments, o is 0, 1, 2, 3, 4, 5, or 6.

[0565] In some embodiments, o is 0, 1, 2, or 3.

[0566] In some embodiments, o is 1 or 2.

[0567] In some embodiments, o is 1.

[0568] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0569] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0570] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0571] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0572] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0573] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0574] In some embodiments, R1 and R2 are methyl.

[0575] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0576] In some embodiments, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0577] In some embodiments, Y 1 , Y 2 , and Y 3 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0578] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2H.

[0579] In some embodiments, at least one of Y1, Y2, and Y3 is alkyl-CO2NH2.

[0580] In some embodiments, at least one of Y 1 , Y 2 , and Y 3 is alkyl-N(alkyl-CO 2 H) 2 .

[0581] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-CO2H.

[0582] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-CO2NH2.

[0583] In some embodiments, at least one of Y1, Y2, and Y3 is -CH2-N(alkyl-CO2H)2.

[0584] In some embodiments, at least two of Y1, Y2, and Y3 are the same.

[0585] In some embodiments, at least three of Y1, Y2, Y3, and Y4 are the same.

[0586] In some embodiments, Y1, Y2 and Y3 are the same.

[0587] In some embodiments, at least one of Y 1 , Y 2 , and Y 3 is H.

[0588] In some embodiments, none of Y 1 , Y 2 and Y 3 is H.

[0589] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0590] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0591] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0592] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0593] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0594] In some embodiments, Y and Y are [ka] and Y2 and / or Y4 are [ka] is.

[0595] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0596] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0597] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0598] In some embodiments, the chemical linker L is PEG.

[0599] In some embodiments, the chemical linker L has the following structure: [ka]

[0600] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0601] In some embodiments, the chemical linker L has the following structure: [ka] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0602] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0603] In some embodiments of the chemical linker, L, m is 3.

[0604] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0605] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0606] In some embodiments, the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0607] In some embodiments, the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0608] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0609] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0610] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0611] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0612] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0613] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0614] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0615] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0616] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0617] In some embodiments, the guest molecule A is a substituted adamantane.

[0618] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0619] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0620] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0621] In some embodiments, the guest molecule A is a substituted diamantane.

[0622] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0623] In some embodiments, guest molecule A is a substituted ferrocene.

[0624] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0625] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0626] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0627] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0628] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0629] In some embodiments, the present invention provides a compound having the structure: [ka]

[0630] (wherein M is a metal, Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl-CO2H), alkyl-N(aryl- alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0631] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0632] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0633] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0634] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0635] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0636] In some embodiments, R4 is -OH.

[0637] In some embodiments, R4 is -NH2.

[0638] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0639] In some embodiments, n and m are each independently 1, 2, or 3.

[0640] In some embodiments, n and m are 1.

[0641] In some embodiments, n is 1, 2, or 3.

[0642] In some embodiments, m is 1, 2, or 3.

[0643] In some embodiments, n is 1 or 2.

[0644] In some embodiments, m is 1 or 2.

[0645] In some embodiments, n is 1.

[0646] In some embodiments, m is 1.

[0647] In some embodiments, n and m are the same.

[0648] In some embodiments, n and m are different.

[0649] In some embodiments, o is 0, 1, 2, 3, 4, 5, or 6.

[0650] In some embodiments, o is 0, 1, 2, or 3.

[0651] In some embodiments, o is 1 or 2.

[0652] In some embodiments, o is 1.

[0653] In some embodiments, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0654] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0655] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0656] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0657] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0658] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0659] In some embodiments, R1 and R2 are methyl.

[0660] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH-COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0661] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0662] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0663] In some embodiments, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0664] In some embodiments, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0665] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[0666] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[0667] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[0668] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[0669] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[0670] In some embodiments, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[0671] In some embodiments, at least two of Y1, Y2 and Y3, Y4 are the same.

[0672] In some embodiments, at least three of Y1, Y2, Y3, and Y4 are the same.

[0673] In some embodiments, Y1, Y2, Y3 and Y4 are the same.

[0674] In some embodiments, Y1, Y2, Y3, and Y4 are each independently -H, [ka] is.

[0675] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0676] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0677] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0678] In some embodiments, Y1, Y2, Y3, and Y4 are each independently: [ka] is.

[0679] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0680] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0681] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0682] In some embodiments, the chemical linker L is PEG.

[0683] In some embodiments, the chemical linker L has the following structure: [ka]

[0684] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0685] In some embodiments, the chemical linker L has the following structure: [ka]

[0686] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0687] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0688] In some embodiments of the chemical linker, L, m is 3.

[0689] In some embodiments, the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0690] In some embodiments, the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0691] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0692] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0693] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0694] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0695] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0696] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0697] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0698] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0699] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0700] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0701] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0702] In some embodiments, the guest molecule A is a substituted adamantane.

[0703] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0704] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0705] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0706] In some embodiments, the guest molecule A is a substituted diamantane.

[0707] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0708] In some embodiments, guest molecule A is a substituted ferrocene.

[0709] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0710] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0711] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0712] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0713] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0714] The present invention relates to a compound having the structure: [ka]

[0715] (wherein M is a metal, L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[0716] The present invention relates to a compound having the structure: [ka]

[0717] (wherein M is a metal, L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[0718] The present invention relates to a compound having the structure: [ka]

[0719] (wherein M is a metal, L is an alkyl linker, an alkyne linker, an alkynal linker, or a polyethylene glycol (PEG), or a combination thereof; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; A is a guest molecule that is adamantane, ferrocene, or diamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[0720] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0721] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0722] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0723] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0724] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0725] In some embodiments, R4 is -OH.

[0726] In some embodiments, R4 is -NH2.

[0727] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0728] In some embodiments, n and m are each independently 1, 2, or 3.

[0729] In some embodiments, n and m are 1.

[0730] In some embodiments, n is 1, 2, or 3.

[0731] In some embodiments, m is 1, 2, or 3.

[0732] In some embodiments, n is 1 or 2.

[0733] In some embodiments, m is 1 or 2.

[0734] In some embodiments, n is 1.

[0735] In some embodiments, m is 1.

[0736] In some embodiments, n and m are the same.

[0737] In some embodiments, n and m are different.

[0738] In some embodiments, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0739] In some embodiments, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0740] In some embodiments, R1 and R2 are each independently C1-C6 alkyl.

[0741] In some embodiments, R1 and R2 are C 1~5 It is alkyl.

[0742] In some embodiments, R1 and R2 are C 1~3 It is alkyl.

[0743] In some embodiments, R1 and R2 are methyl.

[0744] In some embodiments, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0745] In some embodiments, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0746] In some embodiments, the chemical linker L is alkyl or PEG, or a combination thereof.

[0747] In some embodiments, the chemical linker L is PEG.

[0748] In some embodiments, the chemical linker L has the following structure: [ka]

[0749] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0750] In some embodiments, the chemical linker L has the following structure: [ka]

[0751] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0752] In some embodiments of the chemical linker, L, m is 1, 3, or 7.

[0753] In some embodiments of the chemical linker, L, m is 3.

[0754] In some embodiments, alkyl is C 1~6 It is alkyl.

[0755] In some embodiments, alkyl is C 1~3 It is alkyl.

[0756] In some embodiments, the alkyl is methyl.

[0757] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[0758] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.

[0759] In some embodiments, the aryl is phenyl.

[0760] In some embodiments, the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0761] In some embodiments, the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0762] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0763] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0764] In some embodiments, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0765] In some embodiments, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0766] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0767] In some embodiments, the guest molecule A is a substituted or unsubstituted adamantane.

[0768] In some embodiments, the guest molecule A is a substituted or unsubstituted diamantane.

[0769] In some embodiments, the guest molecule A is a substituted or unsubstituted ferrocene.

[0770] In some embodiments, the guest molecule A is an unsubstituted adamantane.

[0771] In some embodiments, the guest molecule A is a substituted adamantane.

[0772] In some embodiments, guest molecule A is 4,9-diaminodiamantane.

[0773] In some embodiments, guest molecule A is unsubstituted ferrocene.

[0774] In some embodiments, the guest molecule A is unsubstituted diamantane.

[0775] In some embodiments, the guest molecule A is a substituted diamantane.

[0776] In some embodiments, the following structure: [ka] Substituted diamantane having the formula:

[0777] In some embodiments, guest molecule A is a substituted ferrocene.

[0778] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0779] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0780] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0781] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0782] In some embodiments, the following structure: [ka] Substituted ferrocenes having the formula:

[0783] The present invention relates to a compound having the structure: [ka]

[0784] (wherein M is a metal, L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2).

[0785] The present invention relates to a compound having the structure: [ka] (In the formula, [ka] is a metal,

[0786] n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0787] The present invention relates to a compound having the structure: [ka] (In the formula, [ka] is a metal,

[0788] n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4, independently at each occurrence, is -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0789] The present invention relates to a compound having the structure: [ka]

[0790] (wherein M is a metal, L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 in each occurrence is independently -OH, -NH2, -O-(C1-C6 alkyl) or -NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2.

[0791] The present invention relates to a compound having the structure: [ka]

[0792] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4 is independently -H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl); X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0793] The present invention relates to a compound having the structure: [ka]

[0794] wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; R4 is, independently in each occurrence, -OH, -NH2, -O-(C1-C6 alkyl), or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH2; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0795] In some embodiments, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0796] In some embodiments, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0797] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0798] In some embodiments, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0799] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0800] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0801] In some embodiments, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0802] The present invention relates to a compound having the structure: [ka]

[0803] (In the formula, [ka] wherein R is a metal.

[0804] In some embodiments, the metal is copper 62( 62 Cu), Copper 64 ( 64 Cu), Copper 67( 67 Cu), Gallium-68( 68 Ga), Scandium-44 ( 44 Sc), Scandium-47( 47 Sc), Scandium-43( 43 Sc), lead 203( 203 Pb), lead 212( 212Pb), Lanthanum 132( 132 La), Lanthanum 135 ( 135 La), Yttrium-86 ( 86 Y), Yttrium 90 ( 90 Y), lutetium-177( 177 Lu), terbium-149 ( 149 Tb), terbium-152( 152 Tb), terbium-155( 155 Tb) or terbium-161( 161 Tb).

[0805] In some embodiments, the metal is copper 62( 62 Cu), Copper 64 ( 64 Cu), Copper 67( 67 Cu), Scandium-44( 44 Sc), Scandium-47( 47 Sc) or scandium-43( 43 Sc).

[0806] In some embodiments, the metal is copper 64( 64 Cu).

[0807] The present invention provides a pharmaceutical composition comprising a metal complex according to the present invention and a marker bound to a host molecule.

[0808] In some embodiments, the marker is a biological marker.

[0809] In some embodiments, the marker is modified.

[0810] In some embodiments, the marker is unmodified.

[0811] In some embodiments, the marker is a tumor marker or a cancer marker.

[0812] In some embodiments, the tumor marker is prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 27-29 (CA 27-29), lactate dehydrogenase (LDH), or neuron-specific enolase (NSE).

[0813] In some embodiments, the tumor marker is prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), or cancer antigen 27-29 (CA 27-29).

[0814] In some embodiments, the tumor marker is prostate-specific antigen (PSA) or carcinoembryonic antigen (CEA).

[0815] In some embodiments, the tumor marker is carcinoembryonic antigen (CEA).

[0816] In some embodiments, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, cucurbit

[10] uril, cucurbit

[14] uril, cyclodextrin, or calix[5]arene.

[0817] In some embodiments, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, or cucurbit

[10] uril.

[0818] In some embodiments, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, or cucurbit[8]uril.

[0819] In some embodiments, the host molecule comprises cucurbit[7]uril or cucurbit[8]uril.

[0820] In some embodiments, the host molecule is cucurbit[7]uril.

[0821] In some embodiments, the interaction between the host molecule and the guest molecule is a non-covalent interaction.

[0822] In some embodiments, the non-covalent interaction is an ion-ion interaction, an ion-dipole interaction, a dipole-dipole interaction, a hydrogen bond, a cation-π interaction, a π-π interaction, a van der Waals interaction, or a hydrophobic interaction.

[0823] In some embodiments, the non-covalent interaction is an ion-ion interaction or an der Waals interaction.

[0824] In some embodiments, a metal complex described in the present invention and a host molecule described in the present invention form a high affinity host-guest complex.

[0825] The present invention provides a method for detecting cells in a subject, comprising administering to the subject a marker bound to a host molecule the structure: [ka]

[0826] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; and A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0827] The present invention provides a method for detecting cells in a subject, comprising administering to the subject a marker bound to a host molecule the structure: [ka]

[0828] (wherein M is a metal, Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl-CO2H), alkyl-N(aryl- alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; and A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0829] The present invention provides a method for detecting cells in a subject, comprising administering to the subject a marker bound to a host molecule the structure: [ka]

[0830] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; X is an alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl-thiourea, alkenyl-heteroaryl-thiourea, alkenyl-cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl-heteroaryl-thiourea or alkynyl-cycloalkyl-thiourea; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; and A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane, or a salt or ester thereof.

[0831] In some embodiments of the method, the metal complex comprises: [ka] It's surprising.

[0832] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0833] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0834] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0835] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0836] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0837] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0838] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0839] In some embodiments of the method, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0840] In some embodiments of the method, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0841] In some embodiments of the method, Y 1 , Y 2 , and Y 3 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0842] In some embodiments of the method, at least one of Y1, Y2, Y3 is alkyl-CO2H.

[0843] In some embodiments of the method, at least one of Y1, Y2, Y3 is alkyl-CO2NH2.

[0844] In some embodiments of the method, at least one of Y 1 , Y 2 , and Y 3 is alkyl-N(alkyl-CO 2 H) 2 .

[0845] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-CO2H.

[0846] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-CO2NH2.

[0847] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2.

[0848] In some embodiments of the method, at least two of Y1, Y2 and Y3 are the same.

[0849] In some embodiments of the method, Y1, Y2 and Y3 are the same.

[0850] In some embodiments of the method, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0851] In some embodiments of the method, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0852] In some embodiments of the method, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0853] In some embodiments of the method, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0854] In some embodiments of the method, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0855] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[0856] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[0857] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[0858] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[0859] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[0860] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[0861] In some embodiments of the method, at least two of Y1, Y2, Y3, Y4 are the same.

[0862] In some embodiments of the method, at least three of Y1, Y2, Y3, and Y4 are the same.

[0863] In some embodiments of the method, Y1, Y2, Y3, and Y4 are the same.

[0864] In some embodiments of the method, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0865] In some embodiments of the method, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0866] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independently -H, [ka] is.

[0867] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0868] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0869] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0870] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0871] In some embodiments of the method, Y1 and Y3 are [ka] and Y2 and / or Y4 are [ka] is.

[0872] In some embodiments of the method, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0873] In some embodiments of the method, n and m are each independently 1, 2, or 3.

[0874] In some embodiments of the method, n and m are 1.

[0875] In some embodiments of the method, n is 1, 2, or 3.

[0876] In some embodiments of the method, m is 1, 2, or 3.

[0877] In some embodiments of the method, n is 1 or 2.

[0878] In some embodiments of the method, m is 1 or 2.

[0879] In some embodiments of the method, n is 1.

[0880] In some embodiments of the method, m is 1.

[0881] In some embodiments of the method, n and m are the same.

[0882] In some embodiments of the method, n and m are different.

[0883] In some embodiments of the method, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; and n is 1, 2, 3, 4, 5, or 6.

[0884] In some embodiments of the method, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0885] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0886] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl.

[0887] In some embodiments of the method, R1 and R2 are C 1~5 It is alkyl.

[0888] In some embodiments of the method, R1 and R2 are C 1~3 It is alkyl.

[0889] In some embodiments of the method, R1 and R2 are methyl.

[0890] In some embodiments of the method, R1 and R2 are ethyl.

[0891] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, or an alkenyl-heteroaryl-thiourea.

[0892] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, or an alkyl-cycloalkyl-thiourea.

[0893] In some embodiments of the method, X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea.

[0894] In some embodiments of the method, X is an alkyl-aryl-thiourea.

[0895] In some embodiments of the method, alkyl is C 1~6 It is alkyl.

[0896] In some embodiments of the method, alkyl is C 1~3 It is alkyl.

[0897] In some embodiments of the method, the alkyl is methyl.

[0898] In some embodiments of the method, the alkyl is ethyl.

[0899] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[0900] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.

[0901] In some embodiments of the method, the aryl is phenyl.

[0902] In some embodiments of the method, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0903] In some embodiments of the method, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0904] In some embodiments of the method, the chemical linker L is alkyl or PEG, or a combination thereof.

[0905] In some embodiments of the method, the chemical linker L is PEG.

[0906] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[0907] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0908] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[0909] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[0910] In some embodiments of the method, the chemical linker L is 1, 3, or 7.

[0911] In some embodiments of the method, the chemical linker L is 3.

[0912] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[0913] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[0914] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[0915] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0916] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[0917] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[0918] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[0919] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane.

[0920] In some embodiments of the method, guest molecule A is a substituted or unsubstituted diamantane.

[0921] In some embodiments of the method, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[0922] In some embodiments of the method, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[0923] In some embodiments of the method, guest molecule A is a substituted or unsubstituted ferrocene.

[0924] In some embodiments of the method, the guest molecule A is an unsubstituted adamantane.

[0925] In some embodiments of the method, the guest molecule A is a substituted adamantane.

[0926] In some embodiments of the method, guest molecule A is 4,9-diaminodiamantane.

[0927] In some embodiments of the method, guest molecule A is unsubstituted ferrocene.

[0928] In some embodiments of the method, guest molecule A is unsubstituted diamantane.

[0929] In some embodiments of the method, guest molecule A is a substituted diamantane.

[0930] In some embodiments of the method, the compound has the following structure: [ka] Substituted diamantane having the formula:

[0931] In some embodiments of the method, guest molecule A is a substituted ferrocene.

[0932] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[0933] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[0934] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[0935] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[0936] In some embodiments of the method, the compound has the following structure: [ka] Substituted ferrocenes having the formula:

[0937] In some embodiments of the method, the structure: [ka]

[0938] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[0939] In some embodiments of the method, the metal complex comprises: [ka] It's surprising.

[0940] In some embodiments of the method, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[0941] In some embodiments of the method, n and m are each independently 1, 2, or 3.

[0942] In some embodiments of the method, n and m are 1.

[0943] In some embodiments of the method, n is 1, 2, or 3.

[0944] In some embodiments of the method, m is 1, 2, or 3.

[0945] In some embodiments of the method, n is 1 or 2.

[0946] In some embodiments of the method, m is 1 or 2.

[0947] In some embodiments of the method, n is 1.

[0948] In some embodiments of the method, m is 1.

[0949] In some embodiments of the method, n and m are the same.

[0950] In some embodiments of the method, n and m are different.

[0951] In some embodiments of the method, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; and n is 1, 2, 3, 4, 5, or 6.

[0952] In some embodiments of the method, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[0953] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[0954] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl.

[0955] In some embodiments of the method, R1 and R2 are C 1~5 It is alkyl.

[0956] In some embodiments of the method, R1 and R2 are C 1~3 It is alkyl.

[0957] In some embodiments of the method, R1 and R2 are methyl.

[0958] In some embodiments of the method, R1 and R2 are ethyl.

[0959] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0960] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[0961] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[0962] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[0963] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[0964] In some embodiments of the method, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0965] In some embodiments of the method, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[0966] In some embodiments of the method, Y 1 , Y 2 , and Y 3 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[0967] In some embodiments of the method, at least one of Y1, Y2, Y3 is alkyl-CO2H.

[0968] In some embodiments of the method, at least one of Y1, Y2, Y3 is alkyl-CO2NH2.

[0969] In some embodiments of the method, at least one of Y 1 , Y 2 , and Y 3 is alkyl-N(alkyl-CO 2 H) 2 .

[0970] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-CO2H.

[0971] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-CO2NH2.

[0972] In some embodiments of the method, at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2.

[0973] In some embodiments of the method, at least two of Y1, Y2 and Y3 are the same.

[0974] In some embodiments of the method, at least three of Y1, Y2, Y3, and Y4 are the same.

[0975] In some embodiments of the method, Y1, Y2 and Y3 are the same.

[0976] In some embodiments of the method, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[0977] In some embodiments of the method, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[0978] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independently -H, [ka] is.

[0979] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0980] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0981] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0982] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[0983] In some embodiments of the method, Y1 and Y3 are [ka] and Y2 and / or Y4 are [ka] is.

[0984] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, or an alkenyl-heteroaryl-thiourea.

[0985] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, or an alkyl-cycloalkyl-thiourea.

[0986] In some embodiments of the method, X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea.

[0987] In some embodiments of the method, X is an alkyl-aryl-thiourea.

[0988] In some embodiments of the method, alkyl is C 1~6 It is alkyl.

[0989] In some embodiments of the method, alkyl is C 1~3 It is alkyl.

[0990] In some embodiments of the method, the alkyl is methyl.

[0991] In some embodiments of the method, the alkyl is ethyl.

[0992] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[0993] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.

[0994] In some embodiments of the method, the aryl is phenyl.

[0995] In some embodiments of the method, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[0996] In some embodiments of the method, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[0997] In some embodiments of the method, the chemical linker L is alkyl or PEG, or a combination thereof.

[0998] In some embodiments of the method, the chemical linker L is PEG.

[0999] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1000] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1001] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1002] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1003] In some embodiments of the method, the chemical linker L is 1, 3, or 7.

[1004] In some embodiments of the method, the chemical linker L is 3.

[1005] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[1006] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[1007] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[1008] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[1009] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[1010] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[1011] In some embodiments of the method, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[1012] In some embodiments of the method, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[1013] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[1014] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane.

[1015] In some embodiments of the method, guest molecule A is a substituted or unsubstituted diamantane.

[1016] In some embodiments of the method, guest molecule A is a substituted or unsubstituted ferrocene.

[1017] In some embodiments of the method, the guest molecule A is an unsubstituted adamantane.

[1018] In some embodiments of the method, the guest molecule A is a substituted adamantane.

[1019] In some embodiments of the method, guest molecule A is 4,9-diaminodiamantane.

[1020] In some embodiments of the method, guest molecule A is unsubstituted ferrocene.

[1021] In some embodiments of the method, guest molecule A is unsubstituted diamantane.

[1022] In some embodiments of the method, guest molecule A is a substituted diamantane.

[1023] In some embodiments of the method, the compound has the following structure: [ka] Substituted diamantane having the formula:

[1024] In some embodiments of the method, guest molecule A is a substituted ferrocene.

[1025] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[1026] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[1027] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[1028] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[1029] In some embodiments of the method, the compound has the following structure: [ka] Substituted ferrocenes having the formula:

[1030] In some embodiments of the method, the structure: [ka]

[1031] (wherein M is a metal, Y1, Y2, Y3, and Y4 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl-CO2H), alkyl-N(aryl- alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[1032] In some embodiments of the method, the structure: [ka]

[1033] (wherein M is a metal, Y1, Y2, and Y3 each independently represent -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(aryl) alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkylaryl-OH), alkyl-N(alkylheteroaryl-OH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), alkyl-P(O)(OH), alkylaryl-P(O)(OH) or alkylheteroaryl-P(O)(OH); wherein R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; L is a chemical linker; R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; n and m are each independently 0, 1, 2, 3, 4, 5, or 6, preferably n and m are each independently 1, 2, or 3, more preferably n and m are 1; o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane), or a salt or ester thereof.

[1034] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1035] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1036] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[1037] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[1038] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[1039] In some embodiments of the method, R4 is -OH.

[1040] In some embodiments of the method, R4 is -NH2.

[1041] In some embodiments of the method, n and m are each independently 0, 1, 2, 3, 4, 5, or 6.

[1042] In some embodiments of the method, n and m are each independently 1, 2, or 3.

[1043] In some embodiments of the method, n and m are 1.

[1044] In some embodiments of the method, n is 1, 2, or 3.

[1045] In some embodiments of the method, m is 1, 2, or 3.

[1046] In some embodiments of the method, n is 1 or 2.

[1047] In some embodiments of the method, m is 1 or 2.

[1048] In some embodiments of the method, n is 1.

[1049] In some embodiments of the method, m is 1.

[1050] In some embodiments of the method, n and m are the same.

[1051] In some embodiments of the method, n and m are different.

[1052] In some embodiments of the method, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3; and n is 1, 2, 3, 4, 5, or 6.

[1053] In some embodiments of the method, R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.

[1054] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl or C1-C6 alkenyl.

[1055] In some embodiments of the method, R1 and R2 are each independently C1-C6 alkyl.

[1056] In some embodiments of the method, R1 and R2 are C 1~5 It is alkyl.

[1057] In some embodiments of the method, R1 and R2 are C 1~3 It is alkyl.

[1058] In some embodiments of the method, R1 and R2 are methyl.

[1059] In some embodiments of the method, R1 and R2 are ethyl.

[1060] In some embodiments of the method, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-COR, alkylaryl-NH—COR, alkylaryl-COR, alkylheteroaryl-COR, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkylaryl-COR), alkyl-N(alkylheteroaryl-COR), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[1061] In some embodiments of the method, Y, Y, Y, and Y are each independently alkyl-COH, alkyl-N—(COR), alkyl-N—(alkyl-COR), alkylaryl-COH, alkylheteroaryl-COH, alkyl-N(alkylaryl-COH), alkyl-N(alkylheteroaryl-COH), alkyl-N(alkyl-COH), alkyl-N(alkylaryl-OH)(alkyl-COH), alkyl-N(alkylheteroaryl-OH)(alkyl-COH), or alkylheteroaryl-P(O)(OH).

[1062] In some embodiments of the method, Y 1 , Y 2 , Y 3 , and Y 4 are each independently alkyl-CO 2 H or alkyl-CO 2 NH 2 or alkyl-N(alkyl-CO 2 H) 2 .

[1063] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.

[1064] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.

[1065] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.

[1066] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.

[1067] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.

[1068] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2.

[1069] In some embodiments of the method, at least two of Y1, Y2, Y3, Y4 are the same.

[1070] In some embodiments of the method, at least three of Y1, Y2, Y3, and Y4 are the same.

[1071] In some embodiments of the method, Y1, Y2, Y3, and Y4 are the same.

[1072] In some embodiments of the method, at least one of Y 1 , Y 2 , Y 3 , and Y 4 is H.

[1073] In some embodiments of the method, none of Y 1 , Y 2 , Y 3 and Y 4 is H.

[1074] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independently -H, [ka] is.

[1075] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[1076] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[1077] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[1078] In some embodiments of the method, Y1, Y2, Y3, and Y4 are each independently [ka] is.

[1079] In some embodiments of the method, Y1 and Y3 are [ka] and Y2 and / or Y4 are [ka] is.

[1080] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, or an alkenyl-heteroaryl-thiourea.

[1081] In some embodiments of the method, X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, or an alkyl-cycloalkyl-thiourea.

[1082] In some embodiments of the method, X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea.

[1083] In some embodiments of the method, X is an alkyl-aryl-thiourea.

[1084] In some embodiments of the method, alkyl is C 1~6 It is alkyl.

[1085] In some embodiments of the method, alkyl is C 1~3 It is alkyl.

[1086] In some embodiments of the method, the alkyl is methyl.

[1087] In some embodiments of the method, the alkyl is ethyl.

[1088] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[1089] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.

[1090] In some embodiments of the method, the aryl is phenyl.

[1091] In some embodiments of the method, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[1092] In some embodiments of the method, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[1093] In some embodiments of the method, the chemical linker L is alkyl or PEG, or a combination thereof.

[1094] In some embodiments of the method, the chemical linker L is PEG.

[1095] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1096] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1097] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1098] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1099] In some embodiments of the method, the chemical linker L is 1, 3, or 7.

[1100] In some embodiments of the method, the chemical linker L is 3.

[1101] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[1102] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[1103] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[1104] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[1105] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[1106] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[1107] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[1108] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[1109] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[1110] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane.

[1111] In some embodiments of the method, guest molecule A is a substituted or unsubstituted diamantane.

[1112] In some embodiments of the method, guest molecule A is a substituted or unsubstituted ferrocene.

[1113] In some embodiments of the method, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[1114] In some embodiments of the method, the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N-(alkyl).

[1115] In some embodiments of the method, the guest molecule A is an unsubstituted adamantane.

[1116] In some embodiments of the method, the guest molecule A is a substituted adamantane.

[1117] In some embodiments of the method, guest molecule A is 4,9-diaminodiamantane.

[1118] In some embodiments of the method, guest molecule A is unsubstituted ferrocene.

[1119] In some embodiments of the method, guest molecule A is unsubstituted diamantane.

[1120] In some embodiments of the method, guest molecule A is a substituted diamantane.

[1121] In some embodiments of the method, the compound has the following structure: [ka] Substituted diamantane having the formula:

[1122] In some embodiments of the method, guest molecule A is a substituted ferrocene.

[1123] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[1124] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl).

[1125] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).

[1126] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).

[1127] In some embodiments of the method, the compound has the following structure: [ka] Substituted ferrocenes having the formula:

[1128] In some embodiments of the method, the structure: [ka]

[1129] (wherein M is a metal, L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[1130] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1131] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1132] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[1133] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[1134] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[1135] In some embodiments of the method, R4 is -OH.

[1136] In some embodiments of the method, R4 is -NH2.

[1137] In some embodiments of the method, the structure: [ka]

[1138] (wherein M is a metal, L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[1139] In some embodiments of the method, the structure: [ka]

[1140] (wherein M is a metal, L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[1141] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1142] In some embodiments of the method, R4 is, independently at each occurrence, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.

[1143] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amido, aryl, heteroaryl, or alkyl-CF3.

[1144] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amido.

[1145] In some embodiments of the method, R4 is, independently at each occurrence, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.

[1146] In some embodiments of the method, R4 is -OH.

[1147] In some embodiments of the method, R4 is -NH2.

[1148] In some embodiments of the method, alkyl is C 1~6 It is alkyl.

[1149] In some embodiments of the method, alkyl is C 1~3 It is alkyl.

[1150] In some embodiments of the method, the alkyl is methyl.

[1151] In some embodiments of the method, the alkyl is ethyl.

[1152] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl.

[1153] In some embodiments of the method, the chemical linker L is an alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof.

[1154] In some embodiments of the method, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker, or polyethylene glycol (PEG), or a combination thereof.

[1155] In some embodiments of the method, the chemical linker L is alkyl or PEG, or a combination thereof.

[1156] In some embodiments of the method, the chemical linker L is PEG.

[1157] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1158] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1159] In some embodiments of the method, the chemical linker L has the following structure: [ka]

[1160] wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, preferably m is 1, 2, 3, 4, 5, 6 or 7, more preferably m is 1, 3 or 7.

[1161] In some embodiments of the method, the chemical linker L is 1, 3, or 7.

[1162] In some embodiments of the method, the chemical linker L is 3.

[1163] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[1164] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[1165] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.

[1166] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.

[1167] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, or ferrocene.

[1168] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane or diamantane.

[1169] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.

[1170] In some embodiments of the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.

[1171] In some embodiments of the method, guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.

[1172] In some embodiments of the method, guest molecule A is substituted with halogen, alkyl, -O-(alkyl), or -N-(alkyl).

[1173] In some embodiments of the method, the guest molecule A is a substituted or unsubstituted adamantane.

[1174] In some embodiments of the method, guest molecule A is a substituted or unsubstituted diamantane.

[1175] In some embodiments of the method, guest molecule A is a substituted or unsubstituted ferrocene.

[1176] In some embodiments of the method, the guest molecule A is an unsubstituted adamantane.

[1177] In some embodiments of the method, the guest molecule A is a substituted adamantane.

[1178] In some embodiments of the method, guest molecule A is 4,9-diaminodiamantane.

[1179] In some embodiments of the method, guest molecule A is unsubstituted ferrocene.

[1180] In some embodiments of the method, guest molecule A is unsubstituted diamantane.

[1181] In some embodiments of the method, guest molecule A is a substituted diamantane.

[1182] In some embodiments of the method, the compound has the following structure: [ka] Substituted diamantane having the formula:

[1183] In some embodiments of the method, guest molecule A is a substituted ferrocene.

[1184] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), —NH—(C1-C6 alkyl), —CHF2, —CF3, —OCHF2, or —OCF3.

[1185] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N—(C1-C6 alkyl), —OH, —O—(C1-C6 alkyl), or —NH—(C1-C6 alkyl).

[1186] In some embodiments of the method, the substituted ferrocene is substituted with C1-C6 alkyl or -alkyl-N-(C1-C6 alkyl).

[1187] In some embodiments of the method, the compound has the following structure: [ka] Substituted ferrocenes having the formula:

[1188] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1189] L is alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, or 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[1190] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1191] L is alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is a substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, or 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; R4, independently in each occurrence, is -H, -OH, -NH, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF, -CF, -OCHF, -OCF, amido, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF, or -Si(alkyl); preferably, R4 is -OH, -NH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl); more preferably, R4 is -OH or -NH.

[1192] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1193] L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2.

[1194] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1195] L is a chemical linker; n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH.

[1196] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1197] L is alkyl, alkenyl, alkynyl, alkyl ether, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2.

[1198] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal,

[1199] L is alkyl, alkenyl, alkynyl, alkyl ether, or polyethylene glycol (PEG); n and m are each independently 1, 2, or 3; A is a guest molecule which is adamantane, ferrocene, or diamantane; R4 is -OH, -NH2, -O-(C1-C6 alkyl) or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2.

[1200] In some embodiments of the method, the structure: [ka] A metal complex having the formula:

[1201] In some embodiments of the method, the structure: [ka] (In the formula, [ka] is a metal).

[1202] In some embodiments of the method, the metal is copper 62( 62 Cu), Copper 64 ( 64 Cu), Copper 67( 67 Cu), Gallium-68( 68 Ga), Scandium-44 ( 44 Sc), Scandium-47( 47 Sc), Scandium-43( 43 Sc), lead 203( 203 Pb), lead 212( 212 Pb), Lanthanum 132( 132 La), Lanthanum 135 ( 135La), Yttrium-86 ( 86 Y), Yttrium 90 ( 90 Y), lutetium-177( 177 Lu), terbium-149 ( 149 Tb), terbium-152( 152 Tb), terbium-155( 155 Tb) or terbium-161( 161 Tb).

[1203] In some embodiments of the method, the metal is copper 62( 62 Cu), Copper 64 ( 64 Cu), Copper 67( 67 Cu), Scandium-44( 44 Sc), Scandium-47( 47 Sc) or scandium-43( 43 Sc).

[1204] In some embodiments of the method, the metal is copper 64( 64 Cu).

[1205] The present invention provides a method for detecting cells in a subject, comprising administering an effective amount of a pharmaceutical composition comprising a metal complex according to the present invention and a marker bound to a host molecule.

[1206] In some embodiments of the methods, the marker is a biological marker.

[1207] In some embodiments of the method, the marker is a tumor marker or a cancer marker.

[1208] In some embodiments of the method, the tumor marker is prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 27-29 (CA 27-29), lactate dehydrogenase (LDH), or neuron-specific enolase (NSE).

[1209] In some embodiments of the method, the tumor marker is prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), or cancer antigen 27-29 (CA 27-29).

[1210] In some embodiments of the method, the tumor marker is prostate-specific antigen (PSA) or carcinoembryonic antigen (CEA).

[1211] In some embodiments of the method, the tumor marker is carcinoembryonic antigen (CEA).

[1212] In some embodiments of the method, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, cucurbit

[10] uril, cucurbit

[14] uril, cyclodextrin, or calix[5]arene.

[1213] In some embodiments of the method, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, or cucurbit

[10] uril.

[1214] In some embodiments of the method, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, or cucurbit[8]uril.

[1215] In some embodiments of the method, the host molecule comprises cucurbit[7]uril or cucurbit[8]uril.

[1216] In some embodiments of the method, the host molecule is cucurbit[7]uril.

[1217] In some embodiments of the method, the interaction between the host molecule and the guest molecule is a non-covalent interaction.

[1218] In some embodiments of the method, the non-covalent interaction is an ion-ion interaction, an ion-dipole interaction, a dipole-dipole interaction, a hydrogen bond, a cation-π interaction, a π-π interaction, a van der Waals interaction, or a hydrophobic interaction.

[1219] In some embodiments of the method, the non-covalent interaction is an ion-ion interaction or a van der Waals interaction.

[1220] In some embodiments of the method, a metal complex described in the present invention and a host molecule described in the present invention form a high affinity host-guest complex.

[1221] The present invention provides a method for detecting cells in a subject, comprising administering to the subject containing a guest molecule an effective amount of a marker modified by a host molecule according to the present invention.

[1222] The present invention provides a method for detecting cells in a subject, the method comprising administering to the subject an effective amount of a pharmaceutical composition described in the present invention, and imaging the subject with a molecular imaging device to detect the composition in the subject.

[1223] The present invention provides a method for imaging cells in a subject, comprising: 1) administering to a subject an effective amount of a composition described herein; wherein the composition specifically accumulates in cells in the subject; 2) detecting the location of the composition in the subject; and 3) obtaining an image of a cell in the subject based on the location of the composition in the subject; and The present invention provides a method comprising:

[1224] The present invention provides a method for detecting the presence of a cell in a subject, the method comprising determining whether an amount of a composition described in the present invention is present in the subject a certain time after administering the composition to the subject, thereby detecting the presence of the cell based on the amount of the composition determined to be present in the subject.

[1225] In some embodiments of the method, the metal complex and the host molecule are applied simultaneously, or the host molecule is applied first and the metal complex is applied after a period of time.

[1226] In some embodiments of the method, the period of time is 24 hours, 48 ​​hours, 72 hours, 96 hours, 120 hours, or 144 hours.

[1227] In some embodiments of the method, the period of time is 72 hours.

[1228] In some embodiments of the method, the cell is a cancer cell or a tumor cell.

[1229] In some embodiments of the method, the cancer or tumor cells have elevated levels of a protein or antigen, or both.

[1230] In some embodiments of the method, the cancer is lung cancer, breast cancer, prostate cancer, cervical cancer, pancreatic cancer, colon cancer, ovarian cancer, stomach cancer, esophageal cancer, skin cancer, heart cancer, liver cancer, bronchial cancer, testicular cancer, kidney cancer, bladder cancer, spleen cancer, thymus cancer, thyroid cancer, brain cancer, or gallbladder cancer.

[1231] In some embodiments of the method, the cancer is pancreatic cancer.

[1232] In some embodiments of the method, the tumor is a bone tumor, a brain tumor, a malignant soft tissue tumor, an organ tumor, an ovarian germ cell tumor, a glandular tumor, a lymphatic tumor, or a skin tumor.

[1233] In some embodiments of the methods, the subject is a mammal.

[1234] In some embodiments of the methods, the subject is a human.

[1235] In some embodiments of the method, the molecular imaging device is a PET imaging device.

[1236] The present invention provides the use of an effective amount of a metal complex according to the present invention for detecting a cell in a subject, wherein the subject comprises a host molecule.

[1237] The present invention provides the use of an effective amount of a marker bound to a host molecule according to the present invention for detecting a cell in a subject, wherein the subject comprises a guest molecule.

[1238] The present invention provides the use of an effective amount of a composition according to the present invention for imaging a subject with a molecular imaging device and detecting cells in the subject.

[1239] The compounds of the present invention include all hydrates, solvates, and complexes of the compounds used in the present invention. When a chiral or otherwise isomeric center is present in a compound of the present invention, all forms of such isomer(s), including enantiomers and diastereomers, are intended to be encompassed herein. Compounds containing chiral centers may be used as racemic mixtures, enantiomerically enriched mixtures, or racemic mixtures may be separated using known techniques and individual enantiomers used separately. The compounds described in the present invention exist in racemic form or as individual enantiomers. Enantiomers can be separated using known techniques, such as those described in Pure and Applied Chemistry 69, 1469-1474, (1997) IUPAC. When a compound contains an unsaturated carbon-carbon double bond, both the cis (Z) and trans (E) isomers are within the scope of the present invention.

[1240] Exemplary functional groups for Y1, Y2, Y3, and Y4 are described in U.S. Patent Application Publication No. 2021 / 0276971, International Application No. US / 2022 / 078389, and International Application No. PCT / US2023 / 064637, the contents of which are incorporated herein by reference.

[1241] The compounds and metal complexes disclosed and tested in U.S. Patent Application Publication No. 2021 / 0276971, International Application No. US / 2022 / 078389, and International Application No. PCT / US2023 / 064637 can be used to bind guest molecules as disclosed herein, the contents of which are incorporated herein by reference.

[1242] The compounds and metal complexes disclosed and tested in U.S. Patent Application Publication No. 2021 / 0276971, International Application No. US / 2022 / 078389, and International Application No. PCT / US2023 / 064637 can be used to bind guest molecules as disclosed herein for PET imaging in subjects, the contents of which are incorporated herein by reference.

[1243] The compounds of the present invention may have spontaneous tautomeric forms. Where the compounds can exist in tautomeric forms, such as keto-enol tautomers, each tautomeric form, whether existing in equilibrium or predominating in one form, is contemplated as being included in the present invention.

[1244] In the compound structures depicted herein, hydrogen atoms are not shown for carbon atoms having fewer than four bonds to non-hydrogen atoms, however, it is understood that sufficient hydrogen atoms are present on such carbon atoms to satisfy the octet rule.

[1245] The present invention also relates to a method for producing a compound in which an isotope atom is 2 H, and / or the isotope atom 13 Isotopic variants of the compounds disclosed herein are provided, including when C is C. Accordingly, in the compounds provided herein, hydrogen may be enriched with deuterium isotopes. It is understood that the present invention encompasses all such isotopic forms.

[1246] It is understood that the structures described in the above method embodiments may be the same as the structures of the compounds described above.

[1247] Where numerical ranges are recited herein, unless otherwise stated, it is understood that the invention contemplates every integer between the upper and lower limits, inclusive.

[1248] Unless otherwise specified, when the structure of a compound of the present invention contains an asymmetric carbon atom, it is understood that the compound occurs as a racemate, a racemic mixture, and an isolated single enantiomer. All such isomeric forms of these compounds are expressly included in the present invention. Unless otherwise specified, each asymmetric carbon may be in either the R or S configuration. It is therefore understood that isomers arising from such asymmetry (e.g., all enantiomers and diastereomers) are included within the scope of the present invention, unless otherwise indicated. Such isomers can be obtained in substantially pure form by classical separation techniques and stereochemically controlled synthesis, such as that described in "Enantiomers, Racemates and Resolutions" by J. Jacques, A. Collet and S. Wilen, Pub. John Wiley & Sons, NY, 1981. For example, resolution can be achieved by preparative chromatography on a chiral column.

[1249] The present invention is also intended to include all isotopes of atoms found on the compounds disclosed herein.Isotopes include atoms with the same atomic number but different mass numbers.By way of general example and without limitation, hydrogen isotopes include tritium and deuterium.Carbon isotopes include C-13 and C-14.

[1250] Throughout this application, any designation of a carbon in a structure, when used without further designation, is 12 C. 13 C or 14 Note that all isotopes of carbon, such as C, are intended to represent. 13 C or 14 Any compound containing C can specifically have the structure of any of the compounds disclosed herein.

[1251] Also, throughout this application, any designation of hydrogen in a structure, when used without further designation, is 1 H, 2 H or 3 It should be noted that all isotopes of hydrogen, such as H, are intended to represent. 2 H or 3 Any compound containing H may specifically have the structure of any of the compounds disclosed herein.

[1252] Isotopically labeled compounds can generally be prepared by conventional techniques known to those skilled in the art, substituting an appropriate isotopically labeled reagent for an unlabeled reagent.

[1253] In the compounds used in the methods of the present invention, the substituents may be substituted or unsubstituted, unless specifically defined otherwise.

[1254] In the compounds used in the methods of the present invention, the alkyl, heteroalkyl, monocyclic, bicyclic, aryl, heteroaryl, and heterocyclic groups can be further substituted by replacing one or more hydrogen atoms with alternative non-hydrogen groups, including, but not limited to, halo, hydroxy, mercapto, amino, carboxy, cyano, carbamoyl, and aminocarbonyl and aminothiocarbonyl.

[1255] It is understood that the substituents and substitution patterns on the compounds used in the methods of the present invention can be selected by one skilled in the art to provide compounds that are chemically stable and can be easily synthesized from readily available starting materials by techniques known in the art. When a substituent is itself substituted with more than one group, it is understood that these multiple groups can be on the same carbon or on different carbons, so long as a stable structure results.

[1256] In selecting compounds for use in the methods of the present invention, one of skill in the art will recognize that the various substituents, i.e., R1, R2, etc., should be selected according to known principles of chemical structure connectivity.

[1257] As used herein, the term "biological marker" refers to a broad subcategory of medical signs, i.e., objective signs of a medical condition observed externally from the patient that can be accurately and reproducibly measured. Medical signs are in contrast to medical symptoms, which are limited to the patient's own perceived signs of health or illness. In 1998, the Biomarker Definitions Working Group of the U.S. National Institutes of Health defined a biomarker as "a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to therapeutic interventions." The International Programme on Chemical Safety, a collaborative initiative on chemical safety led by the World Health Organization (WHO) in collaboration with the United Nations and the International Labour Organization, defines a biomarker as "any substance, structure, or process that can be measured in the body or its products and that affects or predicts the incidence of an outcome or disease." A broader definition takes into account not only disease incidence and outcome, but also the effects of treatments, interventions, and even unintentional environmental exposures to chemicals, nutrients, etc. In a report on the effectiveness of biomarkers in environmental risk assessment, the WHO states that the true definition of a biomarker "includes almost any measurement that reflects the interaction of a biological system with a potential hazard, which may be chemical, physical, or biological. The response measured may be a functional physiological interaction, a biochemical interaction at the cellular level, or a molecular interaction." Examples of biomarkers include everything from pulse rate and blood pressure to more complex laboratory tests of basic chemistry, blood, and other tissues.

[1258] As used herein, the term "guest-host" refers to a host-guest interaction involving two molecules or substances that can form a complex through unique structural relationships and non-covalent bonds. This type of interaction is also referred to as molecular recognition and is commonly found in biorecognition processes such as enzyme-inhibitor interactions and antigen-antibody interactions.

[1259] As used herein, the term "prostate-specific antigen (PSA)" is normally present in low concentrations in the blood of adult men. Elevated PSA levels in the blood can be an indicator of prostate cancer, but other conditions, such as benign prostatic hyperplasia (BPH) and prostatitis, can also increase PSA levels. PSA levels are used to assess how patients respond to treatment and to identify tumor recurrence.

[1260] As used herein, the term "prostatic acid phosphatase (PAP)" is derived from the prostate gland and is normally present in small amounts in the blood. In addition to prostate cancer, elevated levels of PAP may be an indicator of testicular cancer, leukemia and non-Hodgkin's lymphoma, as well as some non-cancerous conditions.

[1261] As used herein, ovarian cancer is the most common cause of elevated CA 125, but cancers of the uterus, cervix, pancreas, liver, colon, breast, lung, and gastrointestinal tract can also elevate CA 125 levels. Some non-cancerous conditions can also elevate CA 125. CA 125 is primarily used to monitor the treatment of ovarian cancer.

[1262] As used herein, "carcinoembryonic antigen (CEA)" is normally found in small amounts in the blood. Colorectal cancer is the most common cancer that elevates this tumor marker. Several other cancers may also elevate carcinoembryonic antigen levels.

[1263] As used herein, "alpha-fetoprotein (AFP)" is produced by the fetus and is therefore normally elevated in pregnant women. However, AFP is not normally found in the blood of adults. In men and non-pregnant women, elevated levels of AFP may be an indicator of liver cancer, or ovarian or testicular cancer. Non-cancerous conditions may also cause elevated AFP levels.

[1264] As used herein, "human chorionic gonadotropin (HCG)" is another substance normally found during pregnancy and produced by the placenta. If pregnancy is ruled out, HCG can be an indicator of cancer of the testes, ovaries, liver, stomach, pancreas, and lung. Marijuana use can also increase HCG levels.

[1265] As used herein, the "CA 19-9" marker is associated with cancer of the colon, stomach, and bile duct. Elevated levels of CA 19-9 may be an indicator of advanced pancreatic cancer, but are also associated with non-cancerous conditions, including gallstones, pancreatitis, cirrhosis, and cholecystitis.

[1266] As used herein, the "CA 15-3" marker is most useful in assessing the effectiveness of treatment for women with advanced breast cancer. Elevated levels of CA 15-3 are also associated with ovarian, lung, and prostate cancer, as well as non-cancerous conditions such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation can also increase CA 15-3 levels.

[1267] As used herein, the "CA 27-29" marker, like CA 15-3, is used to track the progress of treatment in women with advanced breast cancer. Cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver may also elevate CA 27-29 levels. Non-cancerous conditions associated with this substance include first trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease.

[1268] As used herein, "lactate dehydrogenase (LDH)" is a protein normally found in small amounts throughout the body. Many cancers can increase LDH levels, so it is not useful for identifying specific types of cancer. Measuring LDH levels can be useful for monitoring cancer treatment. Non-cancerous conditions that can increase LDH levels include heart failure, hypothyroidism, anemia, and lung or liver disease.

[1269] As used herein, "neuron-specific enolase (NSE)" is associated with several cancers, but is most often used to monitor the treatment of patients with neuroblastoma or small cell lung cancer.

[1270] As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. Thus, "C1-C n C1-C such as alkyl n is defined to include groups having 1, 2..., n-1 or n carbons in a linear or branched arrangement, specifically including methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, isopropyl, isobutyl, sec-butyl, etc. One embodiment is a C1-C 12 Alkyl, C2-C 12 Alkyl, C3-C 12 Alkyl, C4-C 12 It may be alkyl, etc. "Alkoxy" represents an alkyl group as defined above attached through an oxygen bridge.

[1271] The term "alkenyl" refers to a linear or branched non-aromatic hydrocarbon radical containing at least one carbon-carbon double bond, and up to the maximum possible number of non-aromatic carbon-carbon double bonds may be present. Thus, C2 to C n Alkenyl is defined to include groups having 1, 2...., n-1, or n carbons. For example, "C2-C6 alkenyl" refers to an alkenyl radical having 2, 3, 4, 5, or 6 carbon atoms, respectively, and at least one carbon-carbon double bond, e.g., up to three carbon-carbon double bonds in the case of C6 alkenyl. Alkenyl groups include ethenyl, propenyl, butenyl, and cyclohexenyl. As noted above for alkyl, the straight, branched, or cyclic portion of the alkenyl group may contain double bonds and may be substituted if a substituted alkenyl group is indicated. One embodiment is a C2-C6 alkenyl. 12 Alkenyl, C3-C 12 Alkenyl, C4-C 12It can be alkenyl, and the like.

[1272] The term "alkynyl" refers to a linear or branched hydrocarbon radical containing at least one carbon-carbon triple bond, and up to the maximum possible number of non-aromatic carbon-carbon triple bonds may also be present. Thus, C2-C n Alkynyl is defined to include groups having 1, 2...., n-1, or n carbons. For example, "C2-C6 alkynyl" means an alkynyl radical having 2 or 3 carbon atoms and 1 carbon-carbon triple bond, or 4 or 5 carbon atoms and up to 2 carbon-carbon triple bonds, or 6 carbon atoms and up to 3 carbon-carbon triple bonds. Alkynyl groups include ethynyl, propynyl, and butynyl. As discussed above with respect to alkyl, the straight or branched portion of the alkynyl group may contain triple bonds and may be substituted if a substituted alkynyl group is indicated. One embodiment is a C2-C6 alkynyl radical. n It can be alkynyl. One embodiment is C2-C 12 Alkynyl, C3-C 12 Alkynyl, C4-C 12 It can be alkynyl and the like.

[1273] "Alkylene," "alkenylene," and "alkynylene" are intended to mean divalent alkane, alkene, and alkyne radicals, respectively. It is understood that alkylene, alkenylene, and alkynylene can be linear or branched. Alkylene, alkenylene, and alkynylene can be unsubstituted or substituted.

[1274] As used herein, "heteroalkyl" includes both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms and at least one heteroatom in the chain or branch.

[1275] As used herein, "heterocycle" or "heterocyclyl," as used herein, is intended to mean a 5- to 10-membered non-aromatic ring containing from 1 to 4 heteroatoms selected from the group consisting of O, N, and S, and includes bicyclic groups. Thus, "heterocyclyl" includes, but is not limited to: imidazolyl, piperazinyl, piperidinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, dihydropiperidinyl, tetrahydrothiophenyl, and the like. If the heterocycle contains a nitrogen, it is understood that the corresponding N-oxide thereof is also encompassed by this definition.

[1276] As used herein, "cycloalkyl" is intended to mean a cyclic ring of alkanes containing from 3 to 8 total carbon atoms, or any number within this range (i.e., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl).

[1277] As used herein, "monocyclic ring" includes any stable polyatomic carbon ring of up to 10 atoms, which may be unsubstituted or substituted. Examples of such non-aromatic monocyclic elements include, but are not limited to, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. Examples of such aromatic monocyclic elements include, but are not limited to, phenyl.

[1278] As used herein, a "bicycle" includes any stable polyatomic carbon ring of up to 10 atoms fused to a polyatomic carbon ring of up to 10 atoms, each ring being independently unsubstituted or substituted. Examples of such non-aromatic bicyclic elements include, but are not limited to, decahydronaphthalene. Examples of such aromatic bicyclic elements include, but are not limited to, naphthalene.

[1279] As used herein, "aryl" is intended to mean any stable monocyclic, bicyclic, or polycyclic carbon ring of up to 10 atoms in each ring, in which at least one ring is aromatic and may be unsubstituted or substituted. Examples of such aryl elements include phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydro-naphthyl, indanyl, biphenyl, phenanthryl, anthryl, or acenaphthyl. When the aryl substituent is bicyclic and one ring is non-aromatic, it is understood that attachment is via the aromatic ring.

[1280] As used herein, the term "polycyclic" refers to an unsaturated or partially unsaturated multiple fused ring structure, which may be unsubstituted or substituted.

[1281] The term "arylalkyl" refers to an alkyl group, as defined above, in which one or more bonds to a hydrogen atom therein have been replaced with a bond to an aryl group, as defined above. It is understood that the "arylalkyl" group is linked to a core molecule via a bond from the alkyl group, with the aryl group serving as a substituent on the alkyl group. Examples of arylalkyl moieties include, but are not limited to, benzyl (phenylmethyl), p-trifluoromethylbenzyl (4-trifluoromethylphenylmethyl), 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylpropyl, and the like.

[1282] The term "heteroaryl," as used herein, refers to a stable monocyclic, bicyclic, or polycyclic ring of up to 10 atoms in each ring, in which at least one ring is aromatic and contains 1 to 4 heteroatoms selected from the group consisting of O, N, and S. Bicyclic aromatic heteroaryl groups include a phenyl, pyridine, pyrimidine, or pyridazine ring (a) fused to a 6-membered aromatic (unsaturated) heterocycle having one nitrogen atom, (b) fused to a 5- or 6-membered aromatic (unsaturated) heterocycle having two nitrogen atoms, (c) fused to a 5-membered aromatic (unsaturated) heterocycle having one nitrogen atom with either one oxygen atom or one sulfur atom, or (d) fused to a 5-membered aromatic (unsaturated) heterocycle having one heteroatom selected from O, N, or S.Heteroaryl groups within this definition include benzimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, and the like. aryl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, aziridinyl, 1,4-dioxanyl, hexahydroazepinyl, dihydrobenzimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzophenone ... dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisoxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrazolyl Examples include, but are not limited to, tetrahydrofuranyl, tetrahydrothienyl, acridinyl, carbazolyl, cinnolinyl, quinoxalinyl, pyrazolyl, indolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, isoxazolyl, isothiazolyl, furanyl, thienyl, benzothienyl, benzofuranyl, quinolinyl, isoquinolinyl, oxazolyl, isoxazolyl, indolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, and tetrahydroquinoline.When a heteroaryl substituent is bicyclic and one ring is non-aromatic or does not contain a heteroatom, it is understood to be attached via the aromatic ring or via the ring containing the heteroatom, respectively. When a heteroaryl contains a nitrogen atom, it is understood that the corresponding N-oxide thereof is also encompassed by this definition.

[1283] The term "alkylheteroaryl" refers to an alkyl group, as defined above, in which one or more bonds to a hydrogen atom therein are replaced with a bond to a heteroaryl group, as defined above. It is understood that the "alkylheteroaryl" group is connected to a core molecule via a bond from the alkyl group, with the heteroaryl group acting as a substituent on the alkyl group. Examples of alkylheteroaryl moieties include, but are not limited to, -CH2-(CH4N), -CH2-CH2-(CH4N), and the like.

[1284] The terms "heterocycle" or "heterocyclyl" refer to a monocyclic or polycyclic ring system that may be saturated or contain one or more degrees of unsaturation and that contains one or more heteroatoms. Preferred heteroatoms include N, O, and / or S, including N-oxides, sulfur oxides, and dioxides. The ring is preferably 3-10 membered and saturated or contains one or more degrees of unsaturation. Heterocycles may be unsubstituted or substituted, with multiple degrees of substitution being permissible. Such rings may be optionally fused to one or more of another "heterocyclic" ring(s), heteroaryl ring(s), aryl ring(s), or cycloalkyl ring(s). Examples of heterocycles include, but are not limited to, tetrahydrofuran, pyran, 1,4-dioxane, 1,3-dioxane, piperidine, piperazine, pyrrolidine, morpholine, thiomorpholine, tetrahydrothiopyran, tetrahydrothiophene, 1,3-oxathiolane, and the like.

[1285] Alkyl, alkenyl, alkynyl, aryl, heteroaryl, and heterocyclyl substituents may be substituted or unsubstituted unless specifically defined otherwise. In the compounds of the present invention, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and heteroaryl groups can be further substituted by replacing one or more hydrogen atoms with alternative non-hydrogen groups. These include, but are not limited to, halo, hydroxy, mercapto, amino, carboxy, cyano, and carbamoyl.

[1286] As used herein, the term "halogen" refers to F, Cl, Br and I.

[1287] The terms "substituted," "substituted," and "substituent" refer to functional groups, as defined above, in which one or more bonds to a hydrogen atom have been replaced with a bond to a non-hydrogen or non-carbon atom, so long as normal valences are maintained and the substitution results in a stable compound. Substituted groups also include groups in which one or more bonds to a carbon atom(s) or hydrogen atom(s) have been replaced with one or more bonds, including double or triple bonds, to a heteroatom. Examples of substituents include the above functional groups, as well as halogens (i.e., F, Cl, Br, and I); alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, and trifluoromethyl; hydroxyl; alkoxy groups such as methoxy, ethoxy, n-propoxy, and isopropoxy; aryloxy groups such as phenoxy; arylalkyloxy groups such as benzyloxy (phenylmethoxy) and p-trifluoromethylbenzyloxy (4-trifluoromethylphenylmethoxy); heteroaryloxy groups; sulfonyl groups such as trifluoromethanesulfonyl, methanesulfonyl, and p-toluenesulfonyl; nitro, nitrosyl; mercapto; sulfanyl groups such as methylsulfanyl, ethylsulfanyl, and propylsulfanyl; cyano; amino groups such as amino, methylamino, dimethylamino, ethylamino, and diethylamino; and carboxyl. When multiple substituent moieties are disclosed or claimed, the substituted compound can be independently substituted singly or multiply with one or more of the disclosed or claimed substituent moieties. By independently substituted, it is meant that the (two or more) substituents can be the same or different.

[1288] It is understood that the substituents and substitution patterns on the compounds of this invention can be selected by one skilled in the art to provide compounds that are chemically stable and can be readily synthesized from readily available starting materials by techniques known in the art and the methods set forth below. When a substituent is itself substituted with more than one group, it is understood that these multiple groups can be on the same carbon or on different carbons, so long as a stable structure results.

[1289] In selecting compounds of the present invention, one of ordinary skill in the art will recognize that the various substituents, ie, R1, R2, etc., should be selected according to known principles of chemical structure connectivity.

[1290] The various R groups attached to the aromatic rings of the compounds disclosed herein can be added to the rings by standard procedures, such as those described in Advanced Organic Chemistry: Part B: Reaction and Synthesis, Francis Carey and Richard Sundberg, (Springer) 5th ed. Edition. (2007), the contents of which are incorporated herein by reference.

[1291] The compounds used in the methods of the present invention can be prepared by techniques known in organic synthesis and familiar to those skilled in the art, however, these may not be the only means to synthesize or obtain the desired compounds.

[1292] The compounds used in the method of the present invention are those described in Vogel's Textbook of Practical Organic Chemistry, AI Vogel, AR Tatchell, BS Furnis, AJ Hannaford, PWG Smith, (Prentice Hall) 5 thEdition (1996), March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Michael B. Smith, Jerry March, (Wiley-Interscience) 5 th Edition (2007) and references therein, which are incorporated herein by reference, however, these may not be the only means for synthesizing or obtaining the desired compounds.

[1293] Another aspect of the present invention includes the compounds used in the methods of the present invention as pharmaceutical compositions.

[1294] In some embodiments, the pharmaceutical composition comprises a compound of the invention and a pharmaceutically acceptable carrier.

[1295] As used herein, the term "pharmaceutically active agent" means any substance or compound that is suitable for administration to a subject and that provides biological activity or other direct effect in the treatment, cure, mitigation, diagnosis, or prevention of disease, or that affects the structure or any function of a subject. Pharmaceutically active agents include those listed in the Physicians' Desk Reference (PDR Network, LLC; 64th edition; November 15, 2009) and "Approved Drug Products with Therapeutic Equivalence Evaluations" (US Department of Health and Human Services, 30 thPharmaceutically active agents having pendant carboxylic acid groups are readily available to those skilled in the art of chemical synthesis and can be modified in accordance with the present invention using known standard esterification reactions and methods. If the pharmaceutically active agent does not have a carboxylic acid group, one skilled in the art could design and incorporate into the pharmaceutically active agent a carboxylic acid group that can then be esterified, so long as the modification does not interfere with the biological activity or effect of the pharmaceutically active agent.

[1296] The compounds used in the methods of the present invention may be in the form of salts. As used herein, a "salt" refers to a salt of the present compound modified by making an acid or base salt of the compound. In the case of compounds used to treat infections or diseases caused by pathogens, the salts are pharmaceutically acceptable. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, and alkali or organic salts of acidic residues such as phenols. Salts can be made with organic or inorganic acids. Such acid salts include chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates, and the like. Phenolate salts are alkaline earth metal salts, sodium, potassium, or lithium. In this regard, the term "pharmaceutically acceptable salts" refers to relatively non-toxic inorganic and organic acid or base addition salts of the compounds of the present invention. These salts can be prepared in situ during the final isolation and purification of the compounds of the present invention, or by separately reacting the compounds of the present invention purified in the free base or free acid form with a suitable organic or inorganic acid or base and isolating the salt thus formed. Representative salts include hydrobromide, hydrochloride, sulfate, hydrogensulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactobionate, and laurylsulfonate (see, e.g., Berge et al. (1977) "Pharmaceutical Salts," J. Pharm. Sci. 66:1-19).

[1297] The compounds of the present invention can also form salts with basic amino acids such as lysine and arginine, basic sugars such as N-methylglucamine and 2-amino-2-deoxyglucose, and any other physiologically non-toxic basic substances.

[1298] As used herein, "administration" of an agent can be achieved using any of a variety of methods or delivery systems known to those skilled in the art, such as orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, via liposomes, by inhalation, vaginally, intraocularly, by topical delivery, subcutaneously, intraadiposally, intraarticularly, intrathecally, intraventricularly, intratumorally, or intraparenchymally.

[1299] The compounds used in the methods of the present invention can be administered in various forms, including those detailed herein. Treatment with the compounds can be a component of combination therapy or adjunctive therapy, i.e., a subject or patient in need of a drug is treated or administered with one or more of the compounds in conjunction with another drug for the disease. This combination therapy can be sequential therapy, where the patient is first treated with one drug and then with the other drug, or the two drugs can be administered simultaneously. They can be administered independently by the same route or by two or more different routes of administration, depending on the dosage form used.

[1300] As used herein, a "pharmaceutically acceptable carrier" is a pharmaceutically acceptable solvent, suspending agent, or vehicle for delivering the compound to an animal or human. The carrier may be liquid or solid and is selected taking into account the intended method of administration. Liposomes are also pharmaceutically acceptable carriers, as are sustained release vehicles.

[1301] The dosage of the compound administered in treatment will vary depending on factors such as the pharmacodynamic properties of the particular chemotherapeutic agent and its mode and route of administration; the age, sex, metabolic rate, absorption efficiency, health, and weight of the recipient; the nature and extent of the symptoms; the type of concurrent treatment administered; the frequency of treatment; and the desired therapeutic effect.

[1302] Dosage units of the compounds used in the methods of the present invention may contain a single compound or a mixture with an additional anti-tumor agent. The compounds can be administered in oral dosage forms such as tablets, capsules, pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. The compounds can also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, or introduced directly or locally at the site of disease or lesion, for example, by injection, topical application, or other methods, all using dosage forms known to those skilled in the pharmaceutical arts.

[1303] The compounds used in the methods of the present invention can be administered in admixture with suitable pharmaceutical diluents, fillers, excipients, or in carriers such as novel programmable sustained-release multi-compartment nanospheres (collectively referred to herein as pharmaceutically acceptable carriers), appropriately selected for the intended administration mode and consistent with conventional pharmaceutical practice. The units are in a form suitable for oral, nasal, rectal, topical, intravenous or direct injection, or parenteral administration. The compounds can be administered alone or in admixture with a pharmaceutically acceptable carrier. The carrier can be solid or liquid, and the type of carrier is generally selected based on the type of administration used. The active agent can be co-administered in the form of a tablet or capsule, liposomes, as an agglomerated powder, or in liquid form. Examples of suitable solid carriers include lactose, sucrose, gelatin, and agar. Capsules or tablets can be easily formulated to be easy to swallow or chew. Other solid forms include granules and bulk powders. Tablets may contain suitable binders, lubricants, diluents, disintegrants, colorants, flavoring agents, flow-inducing agents, and melting agents. Examples of suitable liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable oils, fats, alcohols, or other organic solvents, including esters; emulsions, syrups or elixirs; suspensions; solutions and / or suspensions reconstituted from non-effervescent granules; and effervescent preparations reconstituted from effervescent granules. Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifiers, suspending agents, diluents, sweeteners, thickeners, and melting agents. Oral dosage forms optionally contain flavorings and colorants. Parenteral and intravenous forms may contain minerals and other materials to make them compatible with the type of injection or delivery system selected.

[1304] Techniques and compositions for making dosage forms useful in the present invention are described in the following references: 7 Modern Pharmaceutics, Chapters 9 and 10 (Banker & Rhodes, Editors, 1979); Pharmaceutical Dosage Forms: Tablets (Lieberman et al., 1981); Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976); Remington's Pharmaceutical Sciences, 17th ed. (Mack Publishing Company, Easton, Pa., 1985); Advances in Pharmaceutical Sciences (David Ganderton, Trevor Jones, Eds., 1992); Advances in Pharmaceutical Sciences Vol. 7 (David Ganderton, Trevor Jones, James McGinity, Eds., 1995); Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms (Drugs and the Pharmaceutical Sciences, Series 36 (James McGinity, Ed., 1989), Pharmaceutical Particulate Carriers: Therapeutic Applications: Drugs and the Pharmaceutical Sciences, Vol 61 (Alain Rolland, Ed., 1993), Drug Delivery to the Gastrointestinal Tract (Ellis Horwood Books in the Biological Sciences. Series in Pharmaceutical Technology; JG Hardy, SS Davis, Clive G. Wilson, Eds.), Modern Pharmaceutics Drugs and the Pharmaceutical Sciences, Vol. 40 (Gilbert S. Banker, Christopher T. Rhodes, Eds.). All of the above publications are incorporated herein by reference.

[1305] Tablets may contain suitable binders, lubricants, disintegrants, colorants, flavoring agents, flow-inducing agents, and melting agents. For example, for oral administration in unit dosage form of a tablet or capsule, the active drug ingredient can be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as lactose, gelatin, agar, starch, sucrose, glucose, methylcellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol, etc. Suitable binders include starch, gelatin, natural sugars such as glucose or β-lactose, corn syrup, natural and synthetic gums such as gum arabic, gum tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, etc. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, etc. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, etc.

[1306] The compounds used in the methods of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from various phospholipids, such as lecithin, sphingomyelin, proteolipids, protein-encapsulating vesicles, or cholesterol, stearylamine, or phosphatidylcholine. The compounds can be administered as a component of a tissue-targeting emulsion.

[1307] The compounds used in the methods of the present invention can also be coupled to soluble polymers as targetable drug carriers or prodrugs. Such polymers include polyvinylpyrrolidone, pyran copolymers, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethylene oxide polylysine substituted with palmitoyl residues. Furthermore, the compounds can be coupled to classes of biodegradable polymers useful for achieving controlled drug release, such as polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polyε-caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphiphilic block copolymers of hydrogels.

[1308] Gelatin capsules can contain the active ingredient compound and powdered carriers such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as immediate-release products or sustained-release products that provide sustained release of medication over several hours. Compressed tablets can be sugar-coated or film-coated to mask unpleasant tastes and protect the tablet from the atmosphere, or enteric-coated for selective disintegration in the gastrointestinal tract.

[1309] For oral administration in liquid dosage forms, the oral drug components are combined with any oral, non-toxic, pharmaceutically acceptable inert carrier, such as ethanol, glycerol, water, etc. Examples of suitable liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable oils, fats, alcohols, or other organic solvents, including esters, emulsions, syrups or elixirs, suspensions, solutions and / or suspensions reconstituted from non-effervescent granules, and effervescent preparations reconstituted from effervescent granules. Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifiers, suspending agents, diluents, sweeteners, thickeners, and melting agents.

[1310] Liquid dosage forms for oral administration may contain coloring and flavoring agents to increase patient acceptance. Generally, suitable carriers for parenteral solutions are water, a suitable oil, saline, aqueous dextrose (glucose) and related sugar solutions, and glycols such as propylene glycol or polyethylene glycol. Solutions for parenteral administration preferably contain a water-soluble salt of the active ingredient, suitable stabilizers, and, if necessary, buffer substances. Antioxidants such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are suitable stabilizers. Citric acid and its salts, and sodium EDTA are also used. In addition, parenteral solutions may contain preservatives such as benzalkonium chloride, methylparaben or propylparaben, and chlorobutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field.

[1311] The compounds used in the methods of the present invention can also be administered in intranasal form using suitable intranasal vehicles, or via transdermal routes, using transdermal skin patch forms known to those of ordinary skill in the art. When administered in the form of a transdermal delivery system, the dosage administration will generally be continuous rather than intermittent throughout the dosage regimen.

[1312] Parenteral and intravenous forms may contain minerals and other materials, such as solutol and / or ethanol, to make them compatible with the type of injection or delivery system chosen.

[1313] The compounds and compositions of the present invention can be administered in oral dosage forms such as tablets, capsules, pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. The compounds can also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, or directly introduced into an affected area, such as a wound, including a skin ulcer, for example, by topical application, injection, or other methods, all using dosage forms known to those of ordinary skill in the pharmaceutical arts.

[1314] Specific examples of pharmaceutically acceptable carriers and excipients that can be used to formulate oral dosage forms of the present invention are described in U.S. Pat. No. 3,903,297, issued Sep. 2, 1975 to Robert. Techniques and compositions for making dosage forms useful in the present invention are described in the following references: 7 Modern Pharmaceutics, Chapters 9 and 10 (Banker & Rhodes, Editors, 1979), Pharmaceutical Dosage Forms: Tablets (Lieberman et al., 1981), Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976), Remington's Pharmaceutical Sciences, 17th ed. (Mack Publishing Company, Easton, Pa., 1985), Advances in Pharmaceutical Sciences (David Ganderton, Trevor Jones, Eds., 1992), Advances in Pharmaceutical Sciences Vol. 7 (David Ganderton, Trevor Jones, James McGinity, Eds., 1995), Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms (Drugs and the Pharmaceutical Sciences, Series 36 (James McGinity, Ed., 1989), Pharmaceutical Particulate Carriers: Therapeutic Applications: Drugs and the Pharmaceutical Sciences, Vol 61 (Alain Rolland, Ed., 1993), Drug Delivery to the Gastrointestinal Tract (Ellis Horwood Books in the Biological Sciences.Series in Pharmaceutical Technology, JG Hardy, SS Davis, Clive G. Wilson, Eds.), Modem Pharmaceutics Drugs and the Pharmaceutical Sciences, Vol. 40 (Gilbert S. Banker, Christopher T. Rhodes, Eds.). All of the above publications are incorporated herein by reference.

[1315] The active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, powders, and chewing gum, or in liquid dosage forms, such as elixirs, syrups, and suspensions, including, but not limited to, mouthwashes and toothpastes. The active ingredient can also be administered parenterally in sterile liquid dosage forms.

[1316] Solid dosage forms such as capsules and tablets can be enterically coated to prevent the release of active ingredient compounds before they reach the small intestine. Materials that can be used as enteric coatings include, but are not limited to, sugars, fatty acids, proteinaceous substances such as gelatin, waxes, shellac, cellulose acetate phthalate (CAP), methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP), and methyl methacrylate-methacrylic acid copolymer.

[1317] The compounds and compositions of the present invention can be coated onto stents for temporary or permanent implantation in the cardiovascular system of a subject.

[1318] Variations on these general synthetic methods will be readily apparent to those of skill in the art and are considered within the scope of the present invention.

[1319] Each embodiment disclosed herein is contemplated as being applicable to each of the other embodiments disclosed, and thus all combinations of the various elements described herein are within the scope of the invention.

[1320] The present invention will be better understood by reference to the following Experimental Details, however, those skilled in the art will readily appreciate that the specific experiments detailed are merely illustrative of the invention as more fully described in the appended claims.

[1321] The present invention involves a host-guest chemistry-driven CB7-Adma-driven pretargeting platform. Three copper-64-labeled Adma guest molecules (1–3) were synthesized and characterized. The in vivo profile of the ligands in the pretargeting strategy was evaluated using a humanized full-length antibody (CB7-M5A) targeting CB7-modified carcinoembryonic antigen (CEA) as a secondary pretargeting agent. Pretargeting studies were performed in CEA+ and CEA- human pancreatic cancer mouse xenografts. The biodistribution of the pretargeting Adma radioligand was compared with that of a directly radiolabeled antibody labeled with zirconium-89. Dosimetry of the two antibody-based imaging approaches was compared. It was hypothesized that the high stability, mutual affinity, and human compatibility of the proposed CB7-Adma pretargeting agent would provide an excellent foundation for a pretargeting platform.

[1322] Materials and Methods Three copper-64-labeled adamantane guest radioligands were developed and compared for their in vitro stability, lipophilicity, and in vivo plasma half-life. These adamantane radioligands were analyzed for pretargeting using the cucurbit[7]uril-modified carcinoembryonic antigen-targeting full-length antibody hT84.66-M5A as a macromolecular pretargeting agent under two different dosing schedules. These molecules were evaluated for pretargeting in human pancreatic carcinoma BxPC3 and MIAPaCa-2 mouse xenografts using positron emission tomography and in vivo biodistribution. Dosimetry of the cucurbit[7]uril-adamantane pretargeting approach in human males was calculated and compared with that of directly zirconium-89-labeled hT84.66-M5A.

[1323] reagent All reagents were purchased from Sigma-Aldrich unless otherwise noted. p-SCN-Bn-NOTAx3HCl and p-SCN-Bn-deferoxamine were purchased from Macrocyclics. t-BOC-N-amido-PEG3-amine and t-Boc-N-amido-PEG7-amine were obtained from BroadPharm. Cucurbit[7]uril azide (CB7-N3) was synthesized by the Chemical Synthesis Core at Vanderbilt University, Tennessee, USA. M5A (hT84.66-M5A) antibody was received from Dr. Yazaki, City of Hope, California, USA. 89 Zr]Zr(C2O4)2 and [ 64 Cu]CuCl2 was purchased from the Washington University School of Medicine MIR Cyclotron Facility. All cell culture media solutions were purchased from VWR International unless otherwise noted. Reagents for SDS-PAGE and Western blotting were purchased from ThermoFisher Scientific. PBS7.4 solution was prepared from phosphate-buffered saline powder (pH 7.4).

[1324] device 4–9 were purified using a Luna 5 μm C18(2) 100 Å LC column, 250 × 10 mm (Phenomenex) column on a reversed-phase (RP) HPLC setup including an Agilent HPLC 1260 Infinity II LC System, consisting of a 1260 Quat Pump VL, a 1260 DAD WR, and a LabLogic Flow-RAM radio-HPLC detector equipped with a LabLogic Systems Limited NaI detector. The chemical purity of 5, 7, and 9 and the radiochemical purity of 1–3 were measured on the same HPLC instrument using a Kinetex 5 μm EVO C18 100 Å column, 150 × 4.6 mm (Phenomenex) analytical column. 89 The radiochemical purity of [Zr]Zr-DFO-M5A was analyzed using a BioScan AR-2000 radio-TLC scanner. Quality control of CB7-M5A and DFO-M5A was performed using a Cytiva Superdex 200 Increase 10 / 300GL size-exclusion column (SEC) on a BioRad NGC-Chromatography System with a SystemPump 10 and a Multi UV / Vis-Conductivity detector. The log D, blood half-life, cellular internalization, and in vivo biodistribution of the samples were measured using a Hidex Automatic Gamma Counter. The radioactivity of the radiotracer dose was measured using a Capintec Inc. CRC-55tR dose calibrator. 4–9 were characterized using a 500 MHz Bruker Avance III proton nuclear magnetic resonance spectroscopy and a Q-Exactive HF (Thermo-Fisher) Orbi-trap mass spectrometer for high-resolution mass spectrometry.

[1325] Liquid Chromatography The RP HPLC method used to purify 4–9 used 0.1% trifluoroacetic acid (TFA) in HO and 0.1% TFA in acetonitrile as solvent A and solvent B, respectively. The % solvent B remained at 5 for the first minute, then increased to 95% over a 24-minute gradient at a flow rate of 4 mL / min. The RP HPLC method used to determine the radiochemical or chemical purity of 1–3, 5, 7, and 9 used the same solvents as the previous method. The % solvent B remained at 5 for the first minute of the run, followed by a 17-minute gradient from 5 to 95% at a flow rate of 1 mL / min. The final RP HPLC method was used to analyze in vitro plasma stability samples of 1–3. Solvent A and solvent B were HO and acetonitrile. The % solvent B remained at 0 for the first 5 minutes of the run. The % solvent B was then increased to 95% over a 15-minute gradient.

[1326] The FPLC size exclusion method used to analyze the purity of CB7-M5A and DFO-M5A used PBS7.4 as the sole solvent at a flow rate of 0.7 mL / min for 70 min.

[1327] Synthesis of NBOC-ADMA (4) NBOC-ethylenediamine (287 mg, 1.81 mmol, 1 equiv.), adamantane-1-carbaldehyde (306 mg, 1.87 mmol, 1 equiv.), and triethylamine (14.5 mg, 0.14 mmol, 0.1 equiv.) were dissolved in methanol (50 mL). The reaction was stirred at room temperature for 30 minutes, after which sodium triacetoxyborohydride (596 mg, 2.81 mmol, 1.5 equiv.) was added. The reaction solution was stirred at room temperature for 60 minutes, after which the solvent was evaporated. Water (50 mL) was added to the crude product. The aqueous phase was extracted with diethyl ether (3 × 40 mL), followed by evaporation of the combined diethyl ether phases to give an oil. Iodomethane (30 mL) and sodium hydroxide (119 mg, 2.98 mmol, 1.6 equiv.) were added to the reaction vial. The methylation reaction was stirred for 2 hours, followed by evaporation of iodomethane, addition of fresh iodomethane, and a second cycle. The solvent was evaporated and replaced with dichloromethane. Undissolved sodium hydroxide was filtered off, and the dichloromethane was evaporated. The crude NBOC-Adma material was dissolved in acetonitrile (7 mL). The crude product was purified using a UV-Vis-HPLC chromatography system using a C18 semi-preparative column. The product fractions were combined and concentrated. Reaction yield: 60.0% (366 mg). Chemical purity: 95.8%. HRMS(ESI)(+)m / z C 20 H 37 N2O2 + [M] + Calculated value: 337.2850 and measured value: 337.2849. 1 H NMR (500 MHz, methanol d4): 3.580-3524 (m, 2 H), 3.518-3.472 (m, 2 H), 3.237 (s, 6 H), 3.182 (s, 2 H), 2.053 (s, 3 H), 1.863 (d, 6 H), 1.781 (q, 6 H), 1.454 (s, 9 H).

[1328] Synthesis of NOTA-ADMA (5) 4 (44.6 mg, 0.13 mmol) was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (1 mL) and reacted at room temperature for 20 min. The solvent and acid were evaporated, and the deprotected molecule was redissolved in dimethyl sulfoxide (1 mL). p-SCN-Bn-NOTAx3HCl (38.7 mg, 0.07 mmol, 0.5 equiv.) and N,N-diisopropylethylamine (20.0 mg, 0.16 mmol, 1.2 equiv.) were added to the reaction solution and stirred for 1 h. The product was purified on a C18 semi-preparative column and detected at λ = 254 nm using a UV-Vis-HPLC chromatography system. Reaction yield: 24.25 (11.7 mg). Chemical purity: 97.6%. HRMS(ESI)(+)m / z C 35 H 55 N6O6S + [M] + Calculated value: 687.3898 and measured value: 687.3899. 1 H-NMR (500 MHz, methanol d4); 7.343 (d, 2 H), 7.292 (d, 2 H), 4.142 (t, 2 H), 3.992-3.704 (m, 4 H), 3.673 (t, 2 H), 3.477-3.322 (m, 4 H), 3.279 (s, 6 H), 3.228 (s, 4 H), 3.192-3.139 (m, 2 H), 3.138-3.003 (m, 2 H), 2.999-2.902 (m, 1 H), 2.900-2.745 (m, 2 H), 2.744-2.540 (m, 2 H), 2.046 (s, 3 H), 1.868 (d, 6 H), 1.771 (q, 6 H).

[1329] Synthesis of NBOC-PEG3-ADMA (6) Adamantane-1-carbaldehyde (213 mg, 1.3 mmol, 1 equiv.), t-BOC-N-amido-PEG3-amide (356 mg, 1.2 mmol, 1.1 equiv.), and triethylamine (21.2 mg, 0.2 mmol, 0.2 equiv.) were dissolved in methanol (50 mL). The reaction solution was stirred at room temperature for 30 minutes, followed by the addition of sodium triacetoxyborohydride (509 mg, 2.4 mmol, 1.8 equiv.). The reaction was stirred overnight at room temperature. The solvent was evaporated, followed by the addition of diethyl ether (10 mL). The undissolved material was filtered, and the diethyl ether phase was collected and evaporated. The crude material was dissolved in iodomethane (20 mL) along with triethylamine (21.2 mg, 0.2 mmol, 0.2 equiv.) and sodium hydroxide (110 mg, 2.8 mmol, 2 equiv.). The methylation reaction was stirred at room temperature for 2 hours. The iodomethane was evaporated and replaced twice with fresh iodomethane (20 mL). Finally, the iodomethane was evaporated and replaced with dichloromethane. Undissolved sodium hydroxide was filtered off, and the dichloromethane was evaporated. The crude NBOC-PEG3-Adma material was dissolved in acetonitrile (7 mL) and methanol (3 mL). The dissolved material was injected into a UV-Vis-HPLC chromatography system and purified on a C18 semi-preparative column. The product fractions were combined and concentrated. Reaction yield: 68.0% (388 mg). Chemical purity: 99.8%. HRMS(ESI)(+)m / z C 26 H 49 N2O5 + [M] + Calculated value: 469.3636 and measured value: 469.3639. 1 H NMR (500 MHz, methanol d4); 3.977-3.928 (m, 2 H), 3.718-3.636 (m, 8 H), 3.629-3.595 (m, 2 H), 3.497 (t, 2 H), 3.274-3.237 (m, 6 H), 3.236-3.181 (m, 4 H), 2.048 (m, 3 H), 1.861 (d, 6 H), 1.776 (q, 6 H), 1.440 (s, 9 H).

[1330] Synthesis of NOTA-PEG3-ADMA (7) 6 (52 mg, 0.11 mmol, 1 equiv.) was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (2 mL), and the reaction was stirred at room temperature for 20 min. The solvent and acid were evaporated on a rotary evaporator. The material was redissolved in dimethyl sulfoxide (1 mL). 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA; 17.4 mg, 0.03 mmol, 0.3 equiv.) was added to the reaction vial along with N,N-diisopropylethylamine (18.6 mg, 0.14 mmol, 1.3 equiv.). The reaction was stirred for 3 h. The product was purified by UV-Vis-HPLC chromatography using a C18 semi-preparative column. The product fractions were combined and concentrated. Reaction yield: 53.2% (16.1 mg). Chemical purity: 97.2%. HRMS(ESI)(+)m / z C 41 H 67 N6O9S + [M] + Calculated value: 819.4685 and measured value: 819.4755. 1 H-NMR (500 MHz, methanol d4); 7.378 (d, 2 H), 7.276 (d, 2 H), 4.017-3.916 (m, 4 H), 3.916-3.800 (m, 2 H), 3.699 (s, 2 H), 3.728-3.671 (m, 2 H), 3.670-3.650 (m, 8 H), 3.649-3.612 (m, 2 H), 3.434-3.325 (m, 4 H), 3.236 (s, 6 H), 3.209 (s, 4 H), 3.184-3.133 (m, 2 H), 3.131-2.951 (m, 2H), 2.948-2.885 (m, 1 H), 2.882-2.740 (m, 2 H), 2.738-2.572 (m, 2 H), 2.033 (s, 3 H), 1.842 (d, 6 H), 1.762 (q, 6 H).

[1331] Synthesis of NBOC-PEG7-ADMA (8) Adamantane-1-carbaldehyde (188 mg, 1.1 mmol), t-Boc-N-amido-PEG7-amine (215 mg, 0.46 mmol), and triethylamine (21.8 mg, 0.22 mmol) were dissolved in methanol (30 mL). The solution was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (543 mg, 2.56 mmol) was added to the reaction solution, and stirring was continued for 2 hours. The solvent was evaporated, and the crude material was mixed with diethyl ether (10 mL). Undissolved sodium triacetoxyborohydride was filtered off and washed twice with diethyl ether (2 × 10 mL). The diethyl ether phases were combined and concentrated on a rotary evaporator. The crude material (366 mg) was dissolved in iodomethane (10 mL). NaOH (110 mg, 2.75 mmol) was added to the reaction solution. The methylation reaction mixture was stirred at RT for 2 h, followed by evaporation of iodomethane. Additional fresh iodomethane (10 mL) was added to the reaction vial. The iodomethane exchange was repeated two more times. The iodomethane was evaporated off one last time. The crude product was dissolved in ACN (4 mL) and purified on a RP-HPLC C18 semi-preparative column. Due to the lack of UV absorption of the product molecule, all eluted material was collected in fractions. Fractions containing the product were determined by MS. The product fractions were combined and the solvent was evaporated off. Reaction yield: 31.3% (93.1 mg). Chemical purity: 98.9%. HRMS(ESI)(+)m / z C 34 H 65 N2O9 + [M] + Calculated value: 645.4685 and measured value: 645.4679. 1 H-NMR (500 MHz, methanol d4); 3.972-3.933 (s, m H), 3.670-3.672 (m, 2 H), 3.671-3.622 (m, 24 H), 3.621-3.598 (m, 2 H), 3.506 (t, 2 H), 3.246 (s, 6 H), 3.233-3.206 (m, 4 H), 2.046 (s, 3 H), 1.858 (d, 6 H), 1.770 (q, 6 H), 1.438 (s, 9 H).

[1332] Synthesis of NOTA-PEG7-ADMA (9) 8 (21.4 mg, 0.033 mmol) was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (0.6 mL). The solution was stirred at RT for 15 min. Dichloromethane and trifluoroacetic acid were evaporated off. The dried material and p-SCN-Bn-NOTA (15.7 mg, 0.028 mmol) were dissolved in dimethyl sulfoxide (1 mL) and mixed with N,N-diisopropylethylamine (18.55 mg, 0.14 mmol). The reaction was stirred at RT for 40 min. The dimethyl sulfoxide was evaporated off under a stream of air at RT overnight. The crude product was dissolved in acetonitrile (2 mL). The product was purified by RP-HPLC C18 semi-preparative column. Reaction yield: 45.0% (12.6 mg). Chemical purity: 95.8%. HRMS(ESI)(+)m / z C 49 H 83 NO 13 S + [M] + Calculated value: 995.5733 and measured value: 995.5724. 1 H-NMR (500 MHz, methanol d4); 7.377 (d, 2 H), 7.270 (d, 2 H), 4.024-3.911 (m, 4 H), 3.910-3.795 (m, 2 H), 3.770 (s, 2 H), 3.694-3.671 (m, 2 H), 3.664-3.614 (m, 24 H), 3.612-3.544 (m, 2 H), 3.429-3.320 (m, 4 H), 3.237 (s, 6 H), 3.214 (s, 4 H), 3.186-3.143 (m, 2 H), 3.141-2.985 (m, 2H), 2.974-2.887 (m, 1 H), 2.886-2.737 (m, 2 H), 2.755-2.544 (m, 2 H), 2.041 (s, 3 H), 1.852 (d, 6 H), 1.771 (q, 6 H).

[1333] In vitro stability of adamantane radioligands.

[1334] [Table 1]

[1335] [Table 2]

[1336] cell culture All cell lines were purchased from ATCC (Manassas, VA). BxPC3 human pancreatic adenocarcinoma cells were maintained in RPMI-1640 medium containing 0.3 g / L glutamine, 25 mM HEPES, 1% (vol / vol) penicillin-streptomycin, and 10% (vol / vol) fetal bovine serum. MIAPaCa-2 human pancreatic carcinoma cells were grown in DMEM / high glucose medium (Sigma-Aldrich) containing 4 mM L-glutamine, 4.5 g / L glucose, sodium pyruvate, 1% (vol / vol) penicillin-streptomycin, 10% (vol / vol) fetal bovine serum, and 2.5% (vol / vol) horse serum (donor group). Both cell lines were maintained at 37°C with 5% CO2 and extracted with 0.25% trypsin-EDTA.

[1337] animal All animals were female nude mice (NU / NU Charles River). Mice were housed in static microisolator cages and provided with corncob bedding (Bed-o'Cobs 1 / 8'' from The Anderson). Diet consisted of Lab Diet 5053 Irradiated PicoLab Rodent Diet 20. Mice were maintained on a 12-hour light / dark cycle. Mice were maintained in a maximum isolation room and their health was monitored quarterly for pathogens and ecto- and endoparasites. For experiments involving xenografts, mice were inoculated with BxPC3 or MIAPaCa-2 cells (5-6 × 10 cells / mL in their respective medium and Matrigel). 6Mice were subcutaneously injected with 150 μL of 100 cells (1:1% V / V). 3 The animals were used after reaching a 90°C (100°F) maximum, which was observed 5–6 weeks after xenograft implantation. All experiments using laboratory animals were conducted in accordance with the Animal Care and Use Committee of Stony Brook Medicine.

[1338] Blood half-life study of ADMA radioligand A total of 3-5 μL of blood was collected from each mouse per time point using capillary tubes (VWR heparinized Micro-Hematocrit tubes).

[1339] For analysis, biphasic decay curves were constructed based on the %ID / g (blood) values ​​plotted as a function of time. At 0 min (x0=0), 100% of the activity was in the blood pool, and the total mass of the blood pool in nude female mice was estimated to be 2 g, so y0 of the curve was set at 50%ID / g. Based on the biphasic decay curves, the percent rapid phase (t 1 / 2fast ) and slow phase (t 1 / 2slow ) was used to calculate the weighted blood half-life of the radioligand according to Equation 1. t 1 / 2 =((t 1 / 2slow ×% fast )+(t 1 / 2fast ×% slow )) / 100 (1)

[1340] Renal excretion of 2 in healthy nude mice Healthy female nude mice (n = 3) were intravenously injected with 2 (7.1 ± 0.3 MBq / nmol; 10.7 ± 0.4 MBq in 150 μL of PBS) via the tail vein. Urine was collected in preweighed Eppendorf tubes 20 and 60 minutes after injection. The tubes were weighed and counted in a gamma counter to determine the %ID / g value for each sample.

[1341] [Table 3]

[1342] Western blotting for carcinoembryonic antigen BxPC3 and MIAPaCa-2 cell lysates were obtained by incubating cells with Cell Lysis Buffer II containing PMSF protease inhibitor and Halt™ protease inhibitor cocktail. Protein quantification was performed using the Pierce™ BCA Protein Assay Kit. Protein lysates were prepared in NuPAGE LDS Sample buffer. Each protein sample (20 μg) was separated by SDS-PAGE using NuPAGE™ 4-12% Bis-Tris, 1.0-1.5 mm Mini Protein Gels at 100 V for 15 minutes, then increased to 150 V for an additional 60 minutes. Proteins were electrophoretically transferred to Invitrolon™ PVDF / Filter Paper Sandwiches at 100 V for 60 minutes. The membrane was blocked with 5% nonfat dry milk in TBS Tween™ 20 buffer for 1 hour and then incubated with primary antibodies overnight at 4°C. The primary antibodies used were CEA monoclonal antibody (H.426.3) (ThermoFisher Scientific), beta Tubulin Loading Control monoclonal antibody (BT7R) (ThermoFisher Scientific), and hT84.66-M5A. The membranes were washed with TBS Tween™ 20 buffer and then incubated with the respective secondary antibodies (Goat anti-Mouse IgG (H+L), Superclonal Recombinant Secondary Antibody, HRP, and Goat anti-human IgG FC Antibody, Horseradish Peroxidase HRP conjugate, cross-absorbed) for 1 hour at room temperature. Western blots were developed using the Pierce™ Fast Western Blot Kit with ECL Substrate. Immunoreactivity was detected using a Konica Minolta SRX-101A Medical Film Processor.

[1343] In vivo biodistribution procedure Mice were euthanized by inhalation of 5% isoflurane at a flow rate of 2.0 mL / min followed by cervical dislocation. Blood, tumor, heart, lungs, stomach, liver, pancreas, spleen, small intestine, large intestine, kidney, muscle, and bone were collected and placed in pre-weighed tubes. Small intestinal and large intestinal contents were collected along with the tissues. To determine the %ID / g value for each organ sample, the samples were weighed and counted in a gamma counter.

[1344] In vivo pretargeting 1, 2, and 3

[1345] [Table 4]

[1346] [Table 5]

[1347] [Table 6]

[1348] [Table 7]

[1349] [Table 8]

[1350] Dosimetry

[1351] [Table 9]

[1352] PET imaging procedure Before each scan, mice were anesthetized with 2.5% isoflurane inhaled at a flow rate of 2.0 mL / min for 5 minutes, and kept anesthetized and warmed with an infrared lamp between scans.

[1353] The 4- and 8-hour imaging studies were performed with 10-minute scans, and the 24-hour images were acquired with 30-minute scans. The energy and time coincidence windows used for the scans were 350 keV to 650 keV and 3.432 ns. Imaging was performed on a Siemens Inveon small animal PET / CT. Data for all possible lines of response (LORs) were saved in raw data format in list mode. The raw data were then binned into 3D sinograms with a span of 3 and a ring difference of 79. Images were scanned using the MAP algorithm with 16 subsets, 18 iterations, and a beta value of 0.00427838, with a voxel size of 0.800000 × 0.800000 × 0.7999150 mm. 3 The images were reconstructed into longitudinal slices (128 × 128 × 159). [Example]

[1354] Development of radiolabeled precursors The detailed synthesis and characterization of the precursors of Adma radioligands 1–3 are described in Figures 6–8. To synthesize 1–3, [ 64 CuCuCl was mixed with 0.2 M NH4OAc (pH 5.5; 50 μL-150 μL) in an Eppendorf tube. The respective precursors of 1, 2, and 3 (1 μL-5 μL in DMSO) were added to the solution, and the reaction was then incubated at room temperature for 10 minutes ("min"). The reaction was monitored using radio-HPLC as described in this invention. Due to the high radiolabeling yield, no purification was required.

[1355] Synthesis and characterization of modified M5A molecules CB7-M5A and deferoxamine-conjugated M5A (DFO-M5A) were prepared as previously described (Jallinoja, 2021 and Jallinoja, 2022). Quality control of both modified antibodies was performed by size-exclusion chromatography, and immunoreactivity was determined by cell-binding and Lindmo assays as previously reported (Jallinoja, 2022 and Lindmo 1986). The number of CB7 moieties per monoclonal antibody (mAb) was determined as previously reported (Jallinoja, 2021).

[1356] DFO-M5A 89 Zr label in 0.1 M oxalic acid (86.2 MBq; 46 μL) 89 Zr]Zr(C2O4)2 was neutralized to pH 7.4 with 1 M NaHCO3. DFO-M5A (900 μg; 6 nmol in 450 μL of phosphate-buffered saline (PBS) at pH 7.4) was added to the zirconium-89 solution, and the labeling reaction was incubated at room temperature for 1 h. The labeling reaction yield was confirmed by radio-thin-layer chromatography (radio-TLC) using iTLC-SG-Glass microfiber chromatography paper and 50 mM ethylenediaminetetraacetic acid as the mobile phase. The synthesized [ 89 [Zr]Zr-DFO-M5A was purified on a PD10 desalting column using PBS as the elution buffer. The radiochemical purity of the purified product was determined using a previously described radio-TLC method.

[1357] In vitro stability and plasma protein binding of 1-3 The in vitro stability of 1–3 was studied in PBS and bovine plasma at 37°C. First, newly synthesized radioligands (1 / 2 / 3; 1.5 nmol; 3.0–3.9 MBq in 100 μL of 0.2 M NHOAc, pH 5.5) were added to an Eppendorf tube with 1 mL of PBS. The samples were incubated at 37°C for 1, 6, or 24 h and then analyzed by radio-high-performance liquid chromatography (radio-HPLC). To study the stability of the ligands in plasma, newly synthesized 1 / 2 / 3 (1.4 MBq in 5 μL of 0.2 M NHOAc, pH 5.5) was mixed with 100 μL of bovine plasma. The samples were incubated at 37°C for 1, 6, or 24 h, followed by the addition of 100 μL of cold acetonitrile. The samples were centrifuged (10,000 rpm) for 5 min. The supernatant was collected and, after a second centrifugation, diluted with HO (300 μL) and subjected to radio-HPLC. The radioactivity of the formed pellet was measured and compared with the initial total activity to determine the protein-bound fraction. Both stability assays were performed in triplicate.

[1358] Partition coefficient measurement of guest radioligand Freshly synthesized 1 / 2 / 3 (586 kBq–610 kBq; 13 μL in 0.2 M NH4OAc, pH 5.5) was added to an Eppendorf tube containing 600 μL of PBS and 600 μL of 1-octanol. The mixture was stirred (900 rpm) in a thermomixer at room temperature for 10 min, and the sample was then centrifuged (1000 rcf) for 5 min. 200 μL of each phase was transferred, and the samples were weighed and counted in a gamma counter to determine the relative amount of radioactivity in each phase. The partition coefficient (log D) value was calculated as log D = log 10 Calculated as (% of radioligand in 1-octanol / % of radioligand in PBS). Experiments were performed in triplicate.

[1359] Interaction of BxPC3 cells with 2 Freshly synthesized 2 (354 kBq; 10 μL) or [ 64Cu]CuCl (407 kBq; 10 μL) was mixed with RPMI-1640 medium containing 0.3 g / L glutamine, 25 mM HEPES, 1% (vol / vol) penicillin-streptomycin, and 10% (vol / vol) fetal bovine serum (12 mL). 6 Each well was weighed and added to a 6-well plate containing BxPC3 cells. The cells were incubated with the medium at 37°C for 2, 4, or 6 hours, and then treated with 0.05 M glycine (pH 2.8). Finally, the cells were lysed by incubation with 1.0 M NaOH. The medium, glycine, and NaOH solutions were collected and measured in a gamma counter to determine the unbound, membrane-bound, and internalized fractions of each radioactive material.

[1360] 1-3 in healthy mice To determine the blood half-life of each Adma radioligand, newly synthesized 1 / 2 / 3 (13.6 MBq–14.8 MBq; 1.5 nmol in 100 μL of PBS) was intravenously injected into healthy female nude mice (n=3). Blood was collected from the saphenous vein at six different time points (2, 5, 15, 30, 60, and 120 min) after injection. The collected blood samples were weighed and measured in a gamma counter to determine the percent injected dose per gram (%ID / g) value for each sample. In addition to studying the blood half-life of each radioligand, early renal excretion of 2 was studied in healthy female nude mice by collecting urine 20 and 60 min after radioligand injection. Further description of both experiments is detailed below.

[1361] Pre-targeting using 1-3 Experimental cohorts (n = 4 or 5 / cohort) of female nude mice bearing BxPC3 tumors were intravenously injected with CB7-M5A (0.7 nmol; 100 μg in 150 μL of PBS), followed 72 h later by intravenous injections of 1 / 2 / 3 (1.5 nmol; 10.2 MBq–13.9 MBq in 150 μL of PBS). For pretargeting with radioligand 2, a 144-h ("h") time lag between antibody and radioligand was also investigated. Cohorts were euthanized for in vivo biodistribution at 4, 8, or 24 h after radioligand injection. The 24-h cohort was also imaged on a small animal PET / computed tomography (PET / CT) scanner (Siemens Inveon) at 4, 8, and 24 h after radioligand injection before euthanasia. An additional cohort / time point for pretargeting 2 was assigned and euthanized 2 hours after radioligand injection for dosimetry calculations. Control cohorts (n=4 / cohort) corresponding to each ligand were injected intravenously with 1 / 2 / 3 alone and sacrificed 24 hours after injection for in vivo biodistribution.

[1362] In tumor models 89 Zr]Zr-DFO-M5A in vivo profile Cohorts of female nude mice bearing BxPC3 and MIAPaCa-2 tumors (n=4 / cohort) were treated with [ 89 [Zr]Zr-DFO-M5A (0.7 nmol; 100 μg; 2.3 MBq–3.4 MBq in 200 μL of PBS) was intravenously injected into mice. Mice were imaged 72 h after injection using a small animal PET / CT scanner, followed by in vivo biodistribution studies.

[1363] Pretargeting with 2 in MIAPaCa-2 xenografts Cohorts of female nude mice (n = 4) bearing MIAPaCa-2 tumors were intravenously injected with CB7-M5A (0.7 nmol; 100 µg in 150 µL of PBS) 72 h prior to injection of 2 (1.5 nmol; 8.8 MBq–10.1 MBq in 150 µL of PBS). Mice were imaged with a small animal PET / CT scanner 24 h after radioligand injection, followed by in vivo biodistribution studies.

[1364] Pretargeting 2 dosimetry The estimated dosimetry of pretargeting 2 in a human adult male (70 kg) was calculated based on the in vivo biodistribution of pretargeting 2 in mice bearing BxPC3 tumors. The biodistribution data were fitted using linear interpolation between time points. To better estimate kinetics, concentrations were interpolated at 1-hour intervals using a linear function for each organ. The integration time was extended to 48 hours, assuming that the %ID / organ was constant after the first 24 hours and that the only change in concentration between 24 and 48 hours was due to radioactive decay. The time interval integral was then obtained using a trapezoidal approximation. The human adult male model was used with the OLINDA program without bladder clearance. 16 These residence times were used to estimate absorbed dose to human subjects using the %ID. The %ID to the large intestine was divided equally between the right and left colon for input into the OLINDA model for adult males. Doses to other parts of the body were not used in this calculation.

[1365] statistical analysis Statistical analysis of all data from biodistribution and in vitro assays was performed using GraphPad Pris (GraphPad Software, Inc.) with an unpaired two-tailed t-test. A p value of p<0.05 between two groups was considered significant. The number of mice used for each pretargeting cohort was at least four. All in vitro experiments were performed in triplicate unless otherwise noted.

[1366] result Development of pretargeting agents The three radioligands were efficiently synthesized and radiolabeled in good yields. The precursors of 1, 2, and 3 were synthesized in overall yields of 14.5%, 36.2%, and 14.1%, respectively, with chemical purities of 97.6%, 97.2%, and 95.8% (Figures 9-11). Radioligands 1-3 were produced by radiolabeling their corresponding precursors in high radiochemical yields of 97.6 ± 1.5%, 98.5 ± 0.7%, and 96.7 ± 0.0%, respectively, with purities of 97.5 ± 1.0%, 98.3 ± 1.8%, and 98.9 ± 0.7% (n = 3) (Figures 12-14).

[1367] The CB7-conjugated antibody was synthesized with an overall recovery of 83%. Each M5A was determined to have an average of 0.8±0.0 CB7 moieties (n=3). Based on the quality control of CB7-M5A, no aggregation or fragmentation was present (FIG. 15). The immunoreactivity of the CB7-conjugated antibody was 95.7±0.7% (n=3).

[1368] In vitro characterization of 1–3 To compare the three radioligands, in vitro analysis was performed on each to determine their relative pharmacological properties and suitability for in vivo pretargeting experiments. 1–3 demonstrated significant in vitro stability in PBS and bovine plasma (Figure 1B, Tables 1 and 2). At 24 h, 95.8 ± 2.2%, 99.0 ± 0.8%, and 95.9 ± 3.1% of 1, 2, and 3 remained intact in PBS, respectively, and 95.2 ± 0.9%, 90.6 ± 1.6%, and 97.5 ± 0.6% of 1, 2, and 3 remained intact in bovine plasma samples. No free copper-64 was observed in any of the stability samples, suggesting that the radioligands are sufficiently stable for their intended application. At the 1-hour time point, Adma radioligand showed decreased plasma binding with increasing polyethylene glycol (PEG) linker length (23.8±6.6 (1), 14.0±5.4 (2), 8.1±2.0 (3)). Furthermore, the percentage of protein-bound radioligand increased with time until the final 24-hour time point (27.8±2.1 (1), 30.5±3.7 (2), 23.2±2.1 (3)). These differences were determined to be non-significant between molecules (p>0.05).

[1369] Based on the cellular internalization assay in BxPC3 cells, 2 did not bind to the cell membrane (0.1±0.1%) or internalize (0.0±0.0%) even after a 6-hour incubation period (Figure 16). 64 Cu]CuCl2 showed significantly higher internalization compared to 2 (5.2 ± 0.3%, p = 0.002), confirming that the copper 64-NOTA complex of 2 remained intact throughout the experimental period.

[1370] Development of DFO-modified antibodies Based on quality control, the DFO-conjugated M5A antibody was intact, with no detectable fragments or aggregates (Figure 15). The overall recovery was 85%. The immunoreactive fraction of DFO-M5A was determined to be 89.6±2.1%, suitable for in vivo analysis.

[1371] 1-3 in healthy mice To determine the pathway and relative rate of clearance of the radioligand, its blood half-life was investigated. Furthermore, because a combination of both renal and hepatobiliary clearance was expected, urine was collected at earlier time points than the initial biodistribution time point. In vivo blood half-life experiments revealed that blood half-life was negatively correlated with the number of PEG units incorporated into the radioligand (Figure 2A, Figure 17). The blood half-life of the ligand decreased with increasing PEG linker length (1: 17.4 min, 2: 13.8 min, 3: 6.1 min). Based on urine samples taken 20 and 60 min after injection of 2 into healthy mice, the radioligand showed high renal clearance at these early time points: 680 ± 210%ID / g and 1050 ± 450%ID / g, respectively (Table 3).

[1372] In vivo biodistribution of pretargeting 1-3 To assess the relative efficacy of the three radioligands for tumor pretargeting in a mouse model, in vivo biodistribution studies were performed. Of the three Adma radioligands studied on a 72-hour time lag schedule, only pretargeting 1 and 2 demonstrated significantly higher tumor uptake compared to their respective control cohorts (1: p=0.005 and 2: p=0.003, Tables 4 and 5). Pretargeting 3 resulted in nearly four-fold higher mean tumor uptake compared to controls (3.9±2.1% ID / g and 0.0±0.0% ID / g; Table 6). However, the tumor uptake between cohorts was not significant (p=0.053). Tumor uptake increased over time in all cohorts, but the highest mean tumor uptake was obtained with pretargeting 2 (1: 8.9 ± 2.0%ID / g, 2: 12.0 ± 0.9%ID / g, and 3: 3.9 ± 2.1%ID / g) (Figure 3). To demonstrate that the pretargeting platform may be suitable for clinical application without the use of clearing agents, we searched for the best radioligand (2) with a time lag of 144 hours, which more closely matches the biological half-life of mAbs in humans. For pretargeting 2, tumor uptake was lower when administered at 144 hours compared with 72 hours after CB7-M5A injection (144 hours: 5.3 ± 1.4%ID / g; p = 0.01), but the tumor-to-blood uptake ratio was substantially higher in the 144-hour cohort (Tables 7 and 8).

[1373] The presence of all Adma radioligands in the blood pool was significantly higher in the pretargeting cohort compared with the corresponding control cohort (p = 0.001, p = 0.0006, and p = 0.01 for 1, 2, and 3, respectively, at the 72-hour time lag), demonstrating that Adma radioligands bind to the remaining CB7-M5A circulating in the blood. However, when the time lag was extended from 72 hours to 144 hours, the presence of pretargeting 2 in the blood was not significantly higher compared with the control study in which only 2 was administered (p = 0.13), suggesting that less 2 binds to CB7-M5A in the blood with longer time lags (Table 7). The lower presence of 2 bound to CB7-M5A circulating in the blood pool likely contributes to the lower tumor uptake of pretargeting 2 at later time points with the extended time lag. First, at the 4 hour time point, tumor uptake of Pretargeting 2 is similar at the 72 hour and 144 hour time lags (3.5±1.1% ID / g and 3.2±1.4% ID / g, respectively).

[1374] All three pretargeting radioligands were excreted from the kidney / bladder and gastrointestinal tract. Pretargeting 3 was excreted the slowest at a 72-hour lag. For pretargeting 2, intestinal elimination was suggested to be slower at a longer 144-hour lag. However, because feces were not removed from the colon samples, the standard deviation of %ID / g values ​​was large in this organ, which may partially explain the differences between the lag cohorts. By 24 hours postinjection, excretion of 1–3 was complete. Despite low renal retention at 4 hours for pretargeting 1–3 (less than 1.0%ID / g; Tables 4–7), 2 showed early renal clearance in healthy mice (Table 3).

[1375] As expected, the tumor-to-blood ratio increased over time with the pretargeting ligand (Table 8). The difference between the first and last time points was significant only for pretargeting 2 at the 72-hour lag (4 hours: 2.3 ± 1.5 and 24 hours: 5.8 ± 0.4; p = 0.008). Due to the low presence of 2 in the blood pool at the 144-hour lag, the highest tumor-to-blood ratio of all conditions studied was obtained 24 hours after injection (16.7 ± 4.6).

[1376] As expected based on the difference in CEA expression in BxPC3 and MIAPaCa-2 cells (Figure 18), tumor uptake of pretargeting 2 was significantly lower in the MIAPaCa-2 tumor model compared to BxPC3 (0.5±0.1%ID / g vs. 12.0±0.9%ID / g; p=0.003), demonstrating the specificity of the radioligand-tumor interaction (Figure 5D).

[1377] Pretargeting PET1-3 PET imaging of pretargeting 1, 2, and 3 in nude mice bearing BxPC3 tumors successfully delineated tumor masses at all time points (Figures 4 and 19). Images confirmed the in vivo biodistribution data, showing that tumor uptake and tumor-to-background signal increased over time until the final time point. At 24 h after radioligand injection, tumor uptake of pretargeting 1–3 varied between 3.8%ID / mL and 17.1%ID / mL, 14.5%ID / mL and 24.0%ID / mL, and 2.8%ID / mL and 13.1%ID / mL, respectively, at a 72-h lag and between 3.8%ID / mL and 7.9%ID / mL at a 144-h lag. For pretargeting 2 in mice bearing MIAPaCa-2 tumors, tumor uptake values ​​ranged from 0.8%ID / mL to 1.4%ID / mL, indicating a lack of tumor-specific uptake due to the lack of CEA expression (Figure 5B).

[1378] In xenograft models 89 In vivo profile of Zr]Zr-DFO-M5A To compare the uptake of M5A in antigen-expressing and antigen-negative cell lines, direct labeling was performed. 89 Zr]Zr-DFO-M5A was used in the subcutaneous tumor model of BxPC3 and MIAPaCa-2 mice. 89 The in vivo profiles of [Zr]Zr-DFO-M5A revealed differences in tumor uptake between the models. This finding is consistent with Western blotting results for CEA expression in the cell lines and previously published results using the same cell lines (Girgis, 2011, Yunis, 1977, and Tan, 1986) (Figure 18). CEA-positive BxPC3 xenografts showed higher tumor uptake compared to CEA-negative MIAPaCa-2 xenografts (53.7 ± 10.0% ID / g vs. 7.3 ± 0.3% ID / g; p = 0.004) (Figure 5C). Based on these imaging experiments, tumor-to-background signal was higher in the BxPC3 cohort compared to MIAPaCa-2, and tumor uptake values ​​in both tumor models confirmed the findings of the in vivo biodistribution study (BxPC3: 50.4 ± 8.9% ID / mL and MIAPaCa-2: 4.8 ± 0.2% ID / g) (Figure 5A).

[1379] Pretargeting 2 dosimetry To determine the dosimetric benefits of the pretargeting method, dosimetry was calculated and directly labeled [ 89 The CB7-Adma pretargeting approach was compared with Zr-DFO-M5A. Based on the estimated doses for adult males with pretargeting 2, the dosimetric analysis was previously reported in a previous study (Jallinoja, 2022). 89 The results showed that the use of [Zr]Zr-DFO-M5A resulted in much lower organ doses (Table 9). In all organs investigated, the dose of pretargeting 2 was reduced several-fold compared to direct radiolabeled M5A. The organ that is often dose-limiting for the use of direct radiolabeled antibodies is the red bone marrow, where [ 89The dose delivered by [Zr]Zr-DFO-M5A was shown to be nearly 70-fold higher compared to pretargeting 2. Reported clinical injection doses of zirconium-89 labeled mAbs vary from 37 MBq to 185 MBq (Ulaner 2017, Der Houven, 2015). In this regard, [ 89 At an estimated clinical dose of 110 MBq for [Zr]Zr-DFO-M5A, the effective dose would be 95.5 mSv. However, at a clinical dose of 150 MBq for Pretargeting 2, the effective dose would be lower at 6.0 mSv, but would still provide the tumor-to-nontarget tissue uptake ratio required to clearly visualize CEA-expressing tumors.

[1380] Essay The present inventors have demonstrated here that host-guest CB7-Adma pretargeted PET can provide specific and exceptionally high tumor uptake and tumor-to-background signal (Figure 3, Tables 4-8). The efficacy of the pretargeting method was evaluated using three copper-64 labeled Adma radioligands. 2, the pretargeting radioligand with the best in vivo profile, was also studied with additional time lags. Because the motivation for the study was the development of a pretargeting platform, direct radiolabeling [ 89 The dosimetry of Zr-DFO-M5A and CB7-M5A pretargeting 2 was compared (Table 9). Although the isotopes were not matched in these experiments, Zr-89 is the most clinically relevant isotope for PET imaging with mAbs, providing information on the biological fate of the mAb 5-7 days after injection, whereas copper-64-based PET with mAbs is only useful for approximately 2 days after injection, where uptake in tumor versus non-target tissues, especially blood, remains very low. 89 Zr]Zr-DFO-M5A was selected.

[1381] Differences between 1 and 3 were observed in their respective blood half-lives and log D values, resulting in ligands with varying tumor uptake and clearance profiles. The number of PEG units incorporated into the Adma radioligands negatively correlated with the compound's log D value and blood half-life. The same correlation between the number of PEG units and log D value was previously observed for ferrocene radioligands designed for pretargeting (Jallinoja, 2022). As previously reported, a higher number of hydrophilic PEG units is expected to result in lower respective log D values ​​(Meyer, 2017).

[1382] The log D values ​​of 1–3 negatively correlated with the blood half-life values. This tendency that more hydrophilic compounds diffuse from the bloodstream through cell membranes at a slower rate, resulting in longer blood half-lives, has been previously established (Obach, 2008; Lewis, 2019). Despite the relative differences in blood half-lives, the difference in tumor uptake between pretargeting 1 and 2 was not significant. However, 3, the Adma radioligand with the shortest blood half-life, exhibited the lowest tumor uptake, which was significantly higher than pretargeting 1 and 2. This positive correlation between blood half-life and tumor uptake has been previously reported by our and other laboratories (Jallinoja, 2022; Meyer, 2017). The longer the radioligand remains in the blood pool, the longer the molecule has to accumulate at the target site.

[1383] M5A exhibits high specificity for CEA, as demonstrated by the direct labeling of M5A ([ 89This was validated in in vivo experiments using [Zr]Zr-DFO-M5A) and pretargeting 2 (Figure 5). Both imaging experiments in the two tumor models demonstrated that the high specificity and excellent tumor-to-background signal provided by antibody-based imaging are not lost when performing antibody imaging with the CB7-Adma pretargeting strategy. The tumor-to-blood ratio of pretargeting 2 obtained 24 hours after injection using the longer time lag schedule of 144 hours was significantly higher than that obtained 72 hours after injection using the [Zr]Zr-DFO-M5A. 89 The dosimetry was higher with Zr-DFO-M5A than with Zr-DFO-M5A (16.7±4.6 and 7.5±1.1, respectively) (Tables 8 and 9). Interestingly, excellent tumor targeting could be achieved with a 144-hour lag, suggesting that even longer lag times may still be possible, further improving dosimetry by reducing exposure in non-target tissues, including blood and bone marrow. This ...

Claims

1. structure: 【Chemical 1】 (In the formula, Y １ , Y ２ , Y ３ , Y ４ are each independently —H, alkyl-N—(CO ２ R ４ ) ２ , alkyl-N-(alkyl-CO ２ R ４ ) ２ , alkylheteroaryl, alkyl-CO ２ H, alkylaryl-CO ２ H, alkylheteroaryl-CO ２ H, alkyl-CO ２ R ４ , alkylaryl-NH—CO ２ R ４ , alkylaryl-CO ２ R ４ , alkylheteroaryl-CO ２ R ４ , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl) ２ , alkyl-N(alkylaryl-CO ２ H) ２ , alkyl-N(alkylheteroaryl-CO ２ H) ２ , alkyl-N(alkylaryl-CO ２ R ４ ) ２ , alkyl-N(alkylheteroaryl-CO ２ R ４ ) ２ , alkyl-N(alkylaryl-OH) ２ , alkyl-N(alkylheteroaryl-OH) ２ , alkyl-N(alkyl-CO ２ H) ２ , alkyl-N(alkylaryl-OH)(alkyl-CO ２ H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO ２ H), alkyl-P(O)(OH) ２ , alkylaryl-P(O)(OH) ２ or alkylheteroaryl-P(O)(OH) ２ and Here, R ４ is independently in each occurrence —H, —OH, —NH ２ , halogen, alkyl, —O-alkyl, —NH-alkyl, —CHF ２ , -CF ３ , -OCHF ２ , -OCF ３ , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF ３ or -Si(alkyl) ３ and preferably, R ４ -OH, -NH ２ , —O—(C １ ~C ６ alkyl) or NH—(C １ ~C ６ alkyl), and more preferably R ４ is -OH or -NH ２ and X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea, an alkenyl-heteroaryl-thiourea, an alkenyl-cycloalkyl-thiourea, an alkynyl-aryl-thiourea, an alkynyl-heteroaryl-thiourea or an alkynyl-cycloalkyl-thiourea; L is a chemical linker; R １ and R ２ are each independently H, halogen, alkyl, alkenyl, alkynyl, —OH, —O-(alkyl), —CHF ２ , -CF ３ , -OCHF ２ or -OCF ３ and n and m are each independently 0, 1, 2, 3, 4, 5, or 6; A is a guest molecule that is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, triamantane, isotetramantane, pentamantane, cyclohexamantane, superadamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamantane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus trioxide, tetramethylenedisulfotetramine, tetrodotoxin, or 1,3,5-triaza-7-phosphaadamantane. or a salt or ester thereof. 【Request 2】 【Chemical 2】 The compound of claim 1 , wherein

3. Y １ , Y ２ , Y ３ , Y ４ each independently represents alkyl-CO ２ H, alkylaryl-CO ２ H, alkyl-N—(CO ２ R ４ ) ２ , alkyl-N-(alkyl-CO ２ R ４ ) ２ , alkylheteroaryl-CO ２ H, alkyl-CO ２ R ４ , alkylaryl-NH—CO ２ R ４ , alkylaryl-CO ２ R ４ , alkylheteroaryl-CO ２ R ４ , alkyl-N(alkylaryl-CO ２ H) ２ , alkyl-N(alkylheteroaryl-CO ２ H) ２ , alkyl-N(alkylaryl-CO ２ R ４ ) ２ , alkyl-N(alkylheteroaryl-CO ２ R ４ ) ２ , alkyl-N(alkyl-CO ２ H) ２ , alkyl-N(alkylaryl-OH)(alkyl-CO ２ H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO ２ H) or alkylheteroaryl-P(O)(OH) ２ and preferably, Y １ , Y ２ , Y ３ , Y ４ each independently represents alkyl-CO ２ H, alkyl-N—(CO ２ R ４ ) ２ , alkyl-N-(alkyl-CO ２ R ４ ) ２ , alkylaryl-CO ２ H, alkylheteroaryl-CO ２ H, alkyl-N(alkylaryl-CO ２ H) ２ , alkyl-N(alkylheteroaryl-CO ２ H) ２ , alkyl-N(alkyl-CO ２ H) ２ , alkyl-N(alkylaryl-OH)(alkyl-CO ２ H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO ２ H) or alkylheteroaryl-P(O)(OH) ２ and more preferably, Y １ , Y ２ , Y ３ , Y ４ each independently represents alkyl-CO ２ H, alkyl-N—(CO ２ R ４ ) ２ , alkyl-N-(alkyl-CO ２ R ４ ) ２ or alkyl-N(alkyl-CO ２ H) ２ and more preferably, Y １ , Y ２ , Y ３ , Y ４ each independently represents alkyl-CO ２ H, CH ２ -N-(CO ２ H) ２ or CH ２ -N-(alkyl-CO ２ R ４ ) ２ 3. The compound according to claim 1 or 2, wherein

4. Y １ , Y ２ and Y ３ At least two of the following are the same, and preferably, Y １ , Y ２ and Y ３ are the same, or Y １ , Y ２ , Y ３ and Y ４ At least two of the following are the same, and preferably, Y １ , Y ２ , Y ３ and Y ４ At least three of the following are the same, and more preferably, Y １ , Y ２ , Y ３ and Y ４ The compound according to any one of claims 1 to 3, wherein

5. 5. The compound according to any one of claims 1 to 4, wherein X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea, an alkyl-cycloalkyl-thiourea, an alkenyl-aryl-thiourea or an alkenyl-heteroaryl-thiourea, preferably X is an alkyl-aryl-thiourea, an alkyl-heteroaryl-thiourea or an alkyl-cycloalkyl-thiourea, more preferably X is an alkyl-aryl-thiourea or an alkyl-heteroaryl-thiourea, and most preferably X is an alkyl-aryl-thiourea.

6. The compound according to any one of claims 1 to 5, wherein the chemical linker L is alkyl, alkenyl, alkynyl, alkyl ether, alkyl thioether, alkylamino, alkylamide, alkyl ester, alkylaryl, alkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, natural amino acid, unnatural amino acid, disulfide or thioether containing linker, or a combination thereof, preferably, the chemical linker L is an alkyl linker, an alkyne linker, an alkynal linker or polyethylene glycol (PEG), or a combination thereof, preferably, the chemical linker L is an alkyl or PEG, or a combination thereof, more preferably, the chemical linker L is PEG.

7. R １ and R ２ are each independently H, halogen, or C １ ~C ６ Alkyl, C １ ~C ６ Alkenyl or C １ ~C ６ alkynyl, preferably R １ and R ２ However, each independently C １ ~C ６ Alkyl or C １ ~C ６ alkenyl, more preferably R １ and R ２ However, each independently C １ ~C ６ alkyl, and more preferably, R １ and R ２ However, each independently C １～５ alkyl, and more preferably, R １ and R ２ However, each independently C １～３ alkyl, and more preferably, R １ and R ２ is ethyl, more preferably R １ and R ２ The compound of any one of claims 1 to 6, wherein is methyl.

8. The compound according to any one of claims 1 to 7, wherein n and m are each independently 0, 1, 2, 3, 4, 5 or 6, preferably n and m are each independently 0, 1, 2 or 3, more preferably n and m are each independently 0 or 1.

9. The compound according to any one of claims 1 to 8, wherein the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diaminodiamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), isane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane, more preferably the guest molecule A is adamantane, ferrocene, 4,9-diaminodiamantane, bicyclo[2.2.2]octane, isane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane, more preferably the guest molecule A is adamantane, 4,9-diaminodiamantane, or ferrocene, and most preferably the guest molecule A is adamantane.

10. Y １ , Y ２ , Y ３ , Y ４ are each independently -H, 【Chemistry 3】 and Preferably Y １ , Y ２ , Y ３ , Y ４ However, each independently, 【Chemistry 4】 and More preferably, Y １ , Y ２ , Y ３ , Y ４ However, each independently, 【Chemistry 5】 and More preferably, Y １ , Y ２ , Y ３ , Y ４ However, each independently, 【Chemistry 6】 and More preferably, Y １ , Y ２ , Y ３ , Y ４ However, each independently, 【Chemistry 7】 and More preferably, Y １ , Y ２ , Y ３ , Y ４ However, each independently, 【Chemistry 8】 The compound according to any one of claims 1 to 9,

11. structure: 【Chemistry 9】 (In the formula, R ４ H, halogen, C １ ~C ６ Alkyl, —OH, —O—(C １ ~C ６ alkyl), -NH-(C １ ~C ６ alkyl), -CHF ２ , -CF ３ , -OCHF ２ or -OCF ３ and preferably, R ４ -OH, -NH ２ , —O—(C １ ~C ６ alkyl) or NH—(C １ ~C ６ alkyl), and more preferably R ４ is -OH or -NH ２ is) The compound according to any one of claims 1 to 9, having the formula:

12. structure: 【Chemistry 10】 wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; 10. The compound of any one of claims 1 to 9, wherein o is 0, 1, 2, 3, 4, 5 or 6, preferably o is 1, 2 or 3, more preferably o is 1.

13. a) alkyl is C １～６ alkyl, preferably alkyl is C １～３ alkyl, more preferably alkyl is methyl or ethyl, more preferably alkyl is methyl; and / or b) aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl, preferably aryl is phenyl, p-toluenyl (4-methylphenyl) or naphthyl, more preferably aryl is phenyl; The compound according to any one of claims 1 to 12.

14. The chemical linker L has the following structure: 【Chemistry 11】 7. The compound of claim 6, having the formula: wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; preferably, m is 1, 2, 3, 4, 5, 6 or 7; more preferably, m is 1, 3 or 7.

15. Substituted ferrocene is C １ ~C ６ Alkyl, -alkyl-N-(C １ ~C ６ alkyl), —OH, —O—(C １ ~C ６ alkyl), -NH-(C １ ~C ６ alkyl), -CHF ２ , -CF ３ , -OCHF ２ or -OCF ３ and preferably the substituted ferrocene is C １ ~C ６ Alkyl, -alkyl-N-(C １ ~C ６ alkyl), —OH, —O—(C １ ~C ６ alkyl), -NH-(C １ ~C ６ alkyl), more preferably the substituted ferrocene is C １ ~C ６ Alkyl, -alkyl-N-(C １ ~C ６ alkyl), and more preferably the substituted ferrocene is -alkyl-N-(C １ ~C ６ alkyl), and most preferably the substituted ferrocene is 【Chemistry 12】 10. The compound of claim 9, wherein:

16. structure: 【Chemistry 13】 2. The compound of claim 1 having the formula:

17. A metal complex comprising the compound according to any one of claims 1 to 16, wherein the compound is coordinated to a metal.

18. structure: 【Chemistry 14】 (In the formula, 【Chemistry 15】 is a metal.

19. The metal is copper 62 ( ６２ Cu), Copper 64 ( ６４ Cu), copper 67 ( ６７ Cu), Gallium 68 ( ６８ Ga), Scandium 44 ( ４４ Sc), Scandium-47 ( ４７ Sc), scandium-43 ( ４３ Sc), lead 203 ( ２０３ Pb), lead 212 ( ２１２ Pb), Lanthanum 132 ( １３２ La), Lanthanum 135 ( １３５ La), Yttrium-86 ( ８６ Y), Yttrium 90 ( ９０ Y), Lutetium 177 ( １７７ Lu), terbium 149 ( １４９ Tb), terbium 152 ( １５２ Tb), terbium 155 ( １５５ Tb) or terbium 161 ( １６１ Tb), and preferably the metal is copper 62 ( ６２ Cu), Copper 64 ( ６４ Cu), copper 67 ( ６７ Cu), Scandium 44 ( ４４ Sc), Scandium-47 ( ４７ Sc) or scandium-43 ( ４３ Sc), and more preferably, the metal is copper 64 ( ６４ 19. The metal complex according to claim 17 or 18, wherein the metal complex is

20. A pharmaceutical composition comprising the metal complex according to any one of claims 17 to 19 and a marker bound to a host molecule.

21. The pharmaceutical composition of claim 20, wherein the marker is a tumor marker or a cancer marker.

22. The tumor marker is prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 27-29 (CA 27-29), lactate dehydrogenase (LDH), or neuron-specific enolase (NSE), and more preferably, the tumor marker is prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), or cancer antigen 27-29 (CA 27-29), more preferably, the tumor marker is prostate-specific antigen (PSA) or carcinoembryonic antigen (CEA), and most preferably, the tumor marker is carcinoembryonic antigen (CEA).

23. 23. The pharmaceutical composition of any one of claims 20 to 22, wherein the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, cucurbit[10]uril, cucurbit[14]uril, cyclodextrin or calix[5]arene; more preferably, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril or cucurbit[10]uril; more preferably, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril or cucurbit[8]uril; more preferably, the host molecule comprises cucurbit[7]uril or cucurbit[8]uril; and most preferably, the host molecule comprises cucurbit[7]uril.

24. The pharmaceutical composition according to any one of claims 20 to 23, wherein the interaction between the host molecule and the guest molecule is a non-covalent interaction, preferably an ion-ion interaction, an ion-dipole interaction, a dipole-dipole interaction, a hydrogen bond, a cation-π interaction, a π-π interaction, a van der Waals interaction or a hydrophobic interaction, more preferably an ion-ion interaction or a van der Waals interaction.

25. The pharmaceutical composition of any one of claims 20 to 24, wherein the metal complex and the host molecule form a high affinity host-guest complex.

26. A method for detecting cells in a subject, the method comprising administering to the subject an effective amount of the metal complex according to any one of claims 17 to 19, the metal complex comprising a marker bound to a host molecule.

27. A method for detecting cells in a subject, the method comprising administering to the subject containing a guest molecule an effective amount of a marker bound to a host molecule according to any one of claims 20 to 25.

28. A method for detecting a cell in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of any one of claims 19 to 24, and imaging the subject with a molecular imaging device to detect the composition in the subject.

29. 1. A method for imaging a cell in a subject, comprising: 1) administering to the subject an effective amount of a composition according to any one of claims 19 to 24; wherein the composition specifically accumulates in the cells in the subject; 2) detecting the location of the composition in the subject; and 3) obtaining an image of cells in the subject based on the location of the composition in the subject; and A method comprising:

30. A method for detecting the presence of a cell in a subject, the method comprising determining whether an amount of a composition described in any one of claims 20 to 25 is present in the subject a certain time after administering the composition to the subject, thereby detecting the presence of the cell based on the amount of the composition determined to be present in the subject.

31. 30. The method of claim 28, wherein the metal complex and the host molecule are applied simultaneously, or the host molecule is applied first and the metal complex is applied after a period of time.

32. 32. The method of claim 31, wherein the period of time is 24 hours, 48 ​​hours, 72 hours, 96 hours, 120 hours or 144 hours, preferably the period of time is 72 hours.

33. The method of any one of claims 26 to 32, wherein the cells are cancer cells or tumor cells.

34. 34. The method of claim 33, wherein the cancer or tumor cells have elevated levels of a protein or antigen, or both.

35. 35. The method of claim 33 or 34, wherein the cancer is lung cancer, breast cancer, prostate cancer, cervical cancer, pancreatic cancer, colon cancer, ovarian cancer, stomach cancer, esophageal cancer, skin cancer, heart cancer, liver cancer, bronchial cancer, testicular cancer, kidney cancer, bladder cancer, spleen cancer, thymus cancer, thyroid cancer, brain cancer or gallbladder cancer.

36. 35. The method of claim 33 or 34, wherein the tumor is a bone tumor, a brain tumor, a malignant soft tissue tumor, an organ tumor, an ovarian germ cell tumor, a glandular tumor, a lymphatic tumor, or a skin tumor.

37. The method of any one of claims 26 to 36, wherein the subject is a mammal, preferably the subject is a human.

38. 29. The method of claim 28, wherein the molecular imaging device is a PET imaging device.

39. Use of an effective amount of the metal complex of any one of claims 17 to 19 for detecting cells in a subject, wherein the subject comprises a marker bound to a host molecule.

40. Use of an effective amount of a host molecule according to any one of claims 20 to 25 for detecting a cell in a subject, wherein the subject comprises a guest molecule.

41. Use of an effective amount of the composition of any one of claims 20 to 26 for imaging a subject with a molecular imaging device and detecting cells in the subject.

42. structure: 【Chemistry 16】 (In the formula, n is 0 or 1; Y １ , Y ２ and Y ３ are each independently alkyl-CO ２ NH ２ , alkyl-N-(alkyl-CO ２ R ４ ) ２ or alkyl-N—(CO ２ R ４ ) ２ and Here, R ４ is independently in each occurrence -H, NH ２ , alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF ３ or -Si(alkyl) ３ and preferably, R ４ are independently —H, NH ２ and Z １ teeth, 【Chemistry 17】 and Here, X １ is NH, O or S, Y ４ Ha-CO ２ H, -CO ２ R ５ , aryl-CO ２ H, heteroaryl-CO ２ H, aryl-CO ２ R ５ or heteroaryl-CO ２ R ５ and Here, R ５ is independently at each occurrence -H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF ３ or -Si(alkyl) ３ and A is a targeting moiety; L is a chemical linker or a pharmaceutically acceptable salt of said compound.

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