Compound, kit and application thereof

Abstract

The invention discloses a compound, a kit and application thereof, and relates to the technical field of biomedicine. The compound comprises an electron acceptor aromatic unit, an optional electron donor aromatic unit and a shielding unit, and the shielding unit shields intermolecular interaction of the electron acceptor aromatic unit and / or the electron donor aromatic unit. Wherein the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit are connected through covalent bonds. The compound can be used as a molecular near-infrared-II fluorophore, and has higher quantum yield and good biocompatibility. The compounds emit fluorescence in the range of 900-1400 nanometers, the intermolecular and intramolecular interaction of the conjugated skeleton is weakened, and the quantum yield is improved. The high quantum yield, biocompatibility and near-infrared II emission of the compound provide opportunities for in-vivo application of near-infrared II imaging by using molecular fluorophores.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a compound, a kit and applications thereof. Background Art

[0002] The emergence of near-infrared II (NIR-II, 1000-1700nm) phototherapy technology has opened up new opportunities for biomedical imaging and treatment. Light in this wavelength range has excellent tissue penetration ability, can effectively penetrate biological tissues, and reduce light scattering, making deep tissue imaging and treatment possible. At the same time, the maximum permissible exposure (MPE) of NIR-II phototherapy technology provides higher safety and effectiveness for clinical applications, which makes it a focus of attention in the fields of tumor treatment, targeted drug delivery, and bioimaging. The selection of appropriate phototherapeutic agents is a key factor in fully utilizing the advantages of NIR-II phototherapy technology. The design of phototherapeutic agents needs to comprehensively consider their efficient optical properties in the NIR-II wavelength range, including fluorescence, photoacoustic, photothermal, and photodynamic properties. These properties not only affect the therapeutic effect, but also determine the distribution, targeting, and biocompatibility of phototherapeutic agents in the body. Therefore, finding molecular phototherapeutic agents with good NIR-II absorption wavelengths (>1000nm) can significantly reduce light scattering and reabsorption, which is the basis for achieving efficient bioimaging and treatment. Compared with inorganic and polymer phototherapeutics, organic molecular phototherapeutics show better controllability and targeted modification capabilities in terms of optical properties. These molecules can be chemically modified or functionalized to enhance their targeting and affinity in specific biological environments, while improving their clearance efficiency and reducing potential toxic reactions. In addition, organic molecular phototherapeutics also show significant advantages in biocompatibility, which can effectively reduce damage to normal tissues, thereby improving the safety of treatment. However, NIR-II phototherapy technology faces complex photophysical process challenges in achieving multimodal treatment. In order to simultaneously achieve fluorescence (radiative transition), photothermal (non-radiative transition) and photodynamic properties (reactive oxygen (ROS) generation), the design and function of phototherapeutics need to be finely regulated. Fluorescence properties can be used for real-time imaging, while photothermal properties can effectively convert light energy into heat energy to kill tumor cells; at the same time, photodynamic properties rely on the generated ROS to cause oxidative stress in cells, further enhancing the therapeutic effect.

[0003] In summary, the advancement of NIR-II phototherapy technology has brought new opportunities to the biomedical field, especially in tumor treatment and deep tissue imaging. By selecting appropriate molecular phototherapeutic agents, combined with their excellent optical properties and biocompatibility, more efficient and safer treatment options are expected. However, at the same time, the scientific research community still needs to face the challenges brought by the realization of multimodal characteristics to promote further development in this field. Summary of the invention

[0004] The following brief summary is not intended to include all features and aspects of the present invention, nor does it mean that the present invention must include all features and aspects discussed in this summary.

[0005] The purpose of the present invention is to provide a variety of high-performance DAD-type molecules with strong NIR-II absorption and powerful energy output through the rational manipulation of molecular planarity, which can be applied to future medical bioimaging, especially in tumor treatment and deep tissue imaging.

[0006] The present invention includes the design, synthesis and application of molecular fluorophores for near-infrared II window biological imaging. Certain molecular fluorophores can be extended to the near-infrared I window. The embodiments of the present disclosure attempt to solve at least one problem existing in the related art to at least some extent, including: 1) low emission quantum yield. 2) limited solubility of molecular fluorophores in aqueous and biological solutions. 3) low efficiency of conjugation with biological molecules (including targeting ligands or antibodies). 4) fluorescence is limited below ~1200 nanometers. The present invention adopts a donor-acceptor-donor structure and a strong acceptor unit to achieve a low band gap of the molecular fluorophore. The introduction of a new donor unit can cause conformational distortion of the conjugated backbone, thereby reducing intermolecular and intramolecular interactions and improving QY. In order to further reduce intermolecular interactions, the present invention introduces a shielding (coating) unit at the end of the conjugated backbone, which can coat the conjugated backbone. The shielding unit and the donor unit can introduce terminal functionalized side chains and conjugate with hydrophilic units (such as PEG) or other targeting ligands through efficient click reactions (such as azide-alkyne cycloaddition reaction).

[0007] An embodiment of a first broad aspect of the present disclosure provides a compound comprising:

[0008] Electron acceptor aromatic unit (also called electron accepting aromatic unit, electron accepting aromatic unit, electron accepting aromatic unit),

[0009] an optional electron donor aromatic unit, and

[0010] a shielding unit, wherein the shielding unit shields the intermolecular interaction of the electron acceptor aromatic unit and / or the electron donor aromatic unit,

[0011] Wherein, the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit are connected by covalent bonds.

[0012] According to some embodiments of the invention, the electron acceptor aromatic unit has a formula selected from any one of the group consisting of:

[0013]

[0014] Each of Z1, Z2, Z3 and Z4 is independently O, S, Se or N, Ti,

[0015] Each R is independently H, C n1 H 2n1+1 or tert-butyloxycarbonyl,

[0016] Each n1 is independently an integer in the range of 1 to 12.

[0017] According to some embodiments of the invention, the electron donor aromatic unit has a formula selected from any one of the group consisting of:

[0018]

[0019] Each Z1 is independently O, S, Se or N, Ti,

[0020] Each of P1 and P2 is independently H, OC n2 H 2n2+1 , C n2 H 2n2+1 , OC n2 H 2n2 B or C n2 H 2n2 Z,

[0021] Each R1 is independently H, C n1 H 2n1+1 or PEG, alkoxy,

[0022] Each X is independently S, Se, NR1 or O,

[0023] Each of Y1 and Y2 is independently H, OC n2 H 2n2+1 , C n2 H 2n2+1 , OC n2 H 2n2 B or C n2 H 2n2 Z,

[0024] each B is independently Br, I, OTs, OMs, ONs, N3 or Ome,

[0025] Each Z is independently Br or N3,

[0026] Each m is independently an integer ranging from 0 to 6,

[0027] Each N2 is independently an integer in the range of 1 to 20,

[0028] Each p is independently an integer ranging from 1 to 20,

[0029] According to some embodiments of the present invention, the shielding unit has a formula selected from any one of the group consisting of:

[0030]

[0031] Each R 2 Independently -(CH 2 ) n3 W,

[0032] Each W is independently H, Br, I, OH, Ots, N 3 ,

[0033] each Z5 is independently S, Se, O or N,

[0034] Each X1 is independently Si, Ge or C,

[0035] Each n3 is independently an integer in the range of 1 to 20,

[0036] Each n is independently an integer ranging from 4 to 120,

[0037] Each b is independently an integer ranging from 1 to 6.

[0038] According to some embodiments of the present invention, the compound comprises two shielding units and two electron donor aromatic units, and the compound has the formula: S'1-D1-A-D2-S'2, wherein

[0039] S'1 represents the first shielding unit,

[0040] S'2 represents the second shielding unit,

[0041] D1 represents the first electron donor aromatic unit,

[0042] D2 represents the second electron donor aromatic unit,

[0043] A represents an electron acceptor aromatic unit.

[0044] According to some embodiments of the invention, the compound has the formula: S'-DA, wherein

[0045] S' represents the shielding unit,

[0046] D represents an electron donor aromatic unit,

[0047] A represents an electron acceptor aromatic unit.

[0048] According to some embodiments of the present invention, the compound includes two electron acceptor aromatic units, three electron donor aromatic units and two shielding units, and the compound has the formula: S'3-D3-A1-D5-A2-D4-S'4, wherein

[0049] S'3 represents the third shielding unit,

[0050] S'4 represents the fourth shielding unit,

[0051] D3 represents the third electron donor aromatic unit,

[0052] D4 represents the fourth electron donor aromatic unit,

[0053] D5 represents the fifth electron donor aromatic unit,

[0054] A1 represents the first electron acceptor aromatic unit,

[0055] A2 represents a second electron acceptor aromatic unit.

[0056] According to some embodiments of the invention, the compound has a formula selected from any one of the group consisting of:

[0057]

[0058]

[0059]

[0060] Each of X, Y, Z1, Z2, Z3, Z4 and Z5 is independently O, S, Se or N,

[0061] Each X1 is independently Si, Ge or C,

[0062] Each of Y1, Y2 and R8 is independently C n2 H 2n2+1 , OC n2 H 2n2+1、 OC n2 H 2n2 B.

[0063]

[0064] each B is independently Br, I, OTs, OMs, ONs, N3 or OMe,

[0065] Each R2 is independently -(CH 2) n3 W1,

[0066] Each W1 is independently N3,

[0067] Each R4 is independently -(CH 2 ) n3 W2,

[0068] Each W2 is independently N3,

[0069] Each R6 is independently -(CH 2 ) n3 W3,

[0070] Each W3 is independently H, N3,

[0071] Each n2 is independently an integer in the range of 2 to 20,

[0072] Each n3 is independently an integer in the range of 2 to 20,

[0073] Each p is independently an integer ranging from 1 to 20,

[0074] Each n is independently an integer ranging from 4 to 120,

[0075] Each b is independently an integer ranging from 1 to 6.

[0076] According to some embodiments of the invention, the compound has a formula selected from any one of the group consisting of:

[0077]

[0078]

[0079]

[0080]

[0081] Among them, each wherein n is independently an integer ranging from 1 to 100.

[0082] An embodiment of the second broad aspect of the present disclosure provides a kit comprising the above-described compound.

[0083] Embodiments of the third broad aspect of the present disclosure provide applications or uses of the above-mentioned compounds or kits in non-disease diagnosis biomedical imaging or labeling of biomacromolecules.

[0084] Among them, the above compounds or kits can be used as molecular fluorescence for non-disease diagnosis biomedical imaging or labeling of biomacromolecules, with enhanced quantum yield and good biocompatibility.

[0085] The fourth broad aspect of the present disclosure provides a method for biomedical imaging for non-disease diagnosis, comprising: applying the above compound or kit to an organism or tissue. By using the above compound as a molecular fluorophore, quantum yield and biocompatibility are significantly improved.

[0086] An embodiment of the fifth broad aspect of the present disclosure provides a method for labeling a biomacromolecule, comprising: reacting the above compound or kit with the biomacromolecule.By using the above compound as a molecular fluorophore, biocompatibility and fluorescence intensity are significantly improved.

[0087] Among them, biological macromolecules include small biologically active molecules (folic acid, trastuzic acid, bile acid, galactose, biotin, etc.), peptides (decapeptide: synB3, ovarian cancer specific binding peptide: OSBP-1 and OSBP-S, etc.), antibody molecules (affibody, erbitux), antigen molecules (affibody, erbitux), antibody molecules (affibody, erbitux), etc.), peptides (decapeptide: synB3, ovarian cancer specific binding peptide: OSBP-1 and OSBP-S, etc.), antibody molecules (affibody, erbitux, anti-SA2, etc.).

[0088]

[0089] The compounds of the present invention can be used as molecular near-infrared-II fluorophores with higher quantum yields and good biocompatibility. These compounds emit fluorescence in the range of 900-1400 nanometers, and the intermolecular and intramolecular interactions of the conjugated backbone are weakened, and the quantum yield is improved. The high quantum yield and biocompatibility of the molecular dyes and their near-infrared-II emission provide opportunities for in vivo applications of near-infrared-II imaging using molecular fluorophores. BRIEF DESCRIPTION OF THE DRAWINGS

[0090] Figure 1 is the compound 4 in Example 1 1 H NMR (nuclear magnetic resonance) spectrum;

[0091] Figure 2 is the compound 4 in Example 1 13 C NMR (nuclear magnetic resonance) spectrum;

[0092] Figure 3 is the HRMS mass spectrum of compound 4 in Example 1;

[0093] Figure 4 is the compound 6 in Example 1 1 H NMR (nuclear magnetic resonance) spectrum;

[0094] Figure 5 is the compound 6 in Example 1 13 C NMR (nuclear magnetic resonance) spectrum;

[0095] Figure 6 is the HRMS mass spectrum of compound 6 in Example 1;

[0096] Figure 7 is the compound 8 in Example 1 1 H NMR (nuclear magnetic resonance) spectrum;

[0097] Figure 8 is the compound 8 in Example 1 13 C NMR (nuclear magnetic resonance) spectrum;

[0098] Fig. 9 IR-FCD-N in Example 1 3 of 1 H NMR (nuclear magnetic resonance) spectrum;

[0099] Fig.10 is the LWTQT in Example 2 1 H NMR (nuclear magnetic resonance) spectrum;

[0100] Fig.11 is the LWTQT in Example 2 13 C NMR (nuclear magnetic resonance) spectrum;

[0101] Fig.12 LWTQT-N in Example 2 3 of 1 H NMR (nuclear magnetic resonance) spectrum;

[0102] Fig.13 is the LWTQT4P in Example 2 1 H NMR (nuclear magnetic resonance) spectrum;

[0103] Fig.14 is the compound 4 in Example 3 1 H NMR (nuclear magnetic resonance) spectrum;

[0104] Fig.15 is the compound 4 in Example 3 13 C NMR (nuclear magnetic resonance) spectrum;

[0105] Fig.16 is the HRMS mass spectrum of compound 4 in Example 3;

[0106] Fig.17 is the compound 7 in Example 3 1 H NMR (nuclear magnetic resonance) spectrum;

[0107] Fig.18 is the compound 7 in Example 3 13 C NMR (nuclear magnetic resonance) spectrum;

[0108] Fig.19 is the HRMS mass spectrum of compound 7 in Example 3;

[0109] Fig. 20 is the IR-BTOG in Example 3 1 H NMR (nuclear magnetic resonance) spectrum;

[0110] Fig.21 is the IR-BTOG in Example 3 13 C NMR (nuclear magnetic resonance) spectrum;

[0111] Fig. 22 is the HRMS mass spectrum of IR-BTOG in Example 3;

[0112] Fig.23 is the compound 12 in Example 4 1 H NMR (nuclear magnetic resonance) spectrum;

[0113] Fig.24 is the compound 12 in Example 4 13 C NMR (nuclear magnetic resonance) spectrum;

[0114] Fig.25 is the HRMS mass spectrum of compound 12 in Example 4;

[0115] Fig.26 is the IR-FEOG in Example 4 1 H NMR (nuclear magnetic resonance) spectrum;

[0116] Fig. 27 is the IR-FEOG in Example 4 13 C NMR (nuclear magnetic resonance) spectrum;

[0117] Fig.28 is the HRMS mass spectrum of IR-FEOG in Example 4;

[0118] Fig.29 is the compound 21 in Example 5 1 H NMR (nuclear magnetic resonance) spectrum;

[0119] Fig.30 is the compound 21 in Example 513 C NMR (nuclear magnetic resonance) spectrum;

[0120] Fig.31 is the HRMS mass spectrum of compound 21 in Example 5;

[0121] Fig.32 is the compound 23 in Example 5 1 H NMR (nuclear magnetic resonance) spectrum;

[0122] Fig.33 is the compound 23 in Example 5 13 C NMR (nuclear magnetic resonance) spectrum;

[0123] Fig.34 is the HRMS mass spectrum of compound 23 in Example 5;

[0124] Fig.35 For LWTQT4P vascular imaging in Example 2 Figure 1 ;

[0125] Fig.36 For LWTQT4P vascular imaging in Example 2 Figure 2 ;

[0126] Fig.37 IR-FCD emission spectrum and quantum yield curve in Example 1;

[0127] Fig.38 The emission spectrum and quantum yield curve of LWTQT4P in Example 2;

[0128] Fig.39 This is the emission spectrum and quantum yield curve of LWTQT in Example 2. DETAILED DESCRIPTION

[0129] In order to facilitate the understanding of those skilled in the art, the present invention is further described below in conjunction with the examples, and the contents mentioned in the examples are not limitations of the present invention. It should be noted in advance that the following examples were completed in the laboratory, and those skilled in the art should understand that the amounts of the components given in the examples only represent the ratio relationship between the components, rather than specific limitations.

[0130] Example 1: IRFCD and IRFCD-N 3 Synthesis

[0131]

[0132] (1) Synthesis of compound 2: Compound 2 was prepared according to the reference “Yang Q, ZMa, HWang, BZhou, SZhu, YZhong, JWang, HWan, AAntaris, RMa, XZhang, JYang, XZhang, HSUn, WLiu, YLiang, HDai, Rational Design of Molecular Fluorophores for Biological Imaging in the NIR-II Window, Adv Mater. 29(12)(2017)1605497. https: / / doi.org / 10.1002 / adma.201605497.”

[0133] (2) Synthesis of Compound 4: Compound 3 (4.00 g, 22.47 mmol) and 1,6-dibromohexane (21.69 g, 88.90 mmol) were added to a 250 mL single-necked flask, followed by 100 mL of 50% w / w KOH solution, and then Bu 4 NBr (0.72 g, 2.22 mmol). The mixture was stirred at 75 ° C for 3 hours under a nitrogen atmosphere. After the reaction, the mixture was returned to room temperature, poured into water, and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate, and the resulting product was purified by silica gel column chromatography to obtain compound 4 as a light brown oil (8.2 g, 72.7%). The H NMR spectrum of compound 4 ( 1 HNMR) Figure 1 As shown, the carbon spectrum ( 13 C NMR) Figure 2 As shown in the high resolution mass spectrometry (HRMS) Figure 3 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.16(d,J=4.9Hz,2H),6.92(d,J=4.9Hz,2H),3.32(t,J=6.8Hz,4H),1.86–1.81(m,4H),1.75–1.69(m,4H),1.30–0.91(m,12H). 13 C NMR (500MHz, CDCl 3 )δ157.73,136.62,124.71,121.52,53.12,37.73,34.01,32.69,29.07,27.91,24.28.HRMS (ESI) for C 21 H 29 Br 2 S 2+ ,([M+H + ]) Calculated value 503.0048, measured value 503.00719.

[0134] (3) Synthesis of Compound 5: Compound 4 (2.50 g, 4.98 mmol) was added to THF (25.00 mL), and n-BuLi (2.50 M, 2.10 mL, 5.25 mmol) solution was gradually added at -78 °C under nitrogen. After stirring for 2.0 hours, tin (IV) chloride (1.7 g, 5.23 mmol) was added. The reaction mixture was then slowly warmed to room temperature and stirred overnight. The mixture was then poured into water and extracted twice with ethyl acetate. The combined organic phases were purified by MgSO 4 Drying and evaporation in vacuo gave compound 5 (3.64 g, 4.60 mmol).

[0135] (4) Synthesis of Compound 6: The obtained stannylation product of Compound 5 (3.64 g, 4.60 mmol) was added to Compound 2 (2.0 g, 3.52 mmol) in a 100 mL single-necked flask. Pd(PPh 3 ) 4 (200mg), then 40mL of dry toluene solvent was added. The mixture was stirred at 130°C for 3 hours. Then, the mixture was cooled to room temperature and poured into water. It was extracted twice with ethyl acetate, and the combined organic phase was dried over anhydrous magnesium sulfate. The crude product was purified by column chromatography using PE / DCM (5:1) as eluent to obtain compound 6 as a yellow-brown solid (2.78g, 79.8%). The H NMR spectrum of compound 6 ( 1 H NMR) Figure 4 As shown, the carbon spectrum ( 13 C NMR) Figure 5 As shown in the high resolution mass spectrometry (HRMS) Figure 6 shown. 1 H NMR (500 MHz, CDCl 3)δ7.69(dd,J=7.3,4.1Hz,2H),7.62(d,J=7.8Hz,1H),7.54(s,1H),7.36–7.30(m,3H),7.25( s,1H),7.19(d,J=4.7Hz,1H),6.95(d,J=4.8Hz,1H),3.34(t,J=6.7Hz,4H),3.27(t,J=6.8Hz ,4H),2.05–1.99(m,4H),1.93–1.86(m,4H),1.74(dd,J=14.4,7.1Hz,4H),1.67–1.63(m,4H) ,1.32(dd,J=15.4,7.5Hz,6H),1.20(d,J=7.5Hz,6H),1.11–1.02(m,6H),0.89–0.83(m,6H). 13 C NMR (500MHz, CDCl 3 )δ158.67,151.29,150.43,140.70,140.39,137.28,136.85,134.31,134.10,133.59,129.05,128.24,127.69,127.15, 127.00,125.07,124.36,124.23,122.99,122.80,121.97,121.56,120.20,119.72,119.14,117.28,77.28,77.03,76.7 8,55.07,54.67,53.66,44.89,40.26,39.20,37.82,34.89,34.02,33.60,32.70,32.63,32.27,31.94,30.76,29.34,29.11,29.04,28.35,27.90,27.74,27.38,24.32,23.92,23.52,23.19,22.71,19.74,14.14,13.91,13.62.HRMS (ESI) for C 46 H 59 Br 4 S 2 + ,([M+H + ])Calculated value 995.0745, measured value 995.0745.

[0136] (5) Synthesis of Compound 7: Compound 6 (2.78 g, 2.81 mmol) was added to THF (15 mL). At -78 °C under nitrogen, n-BuLi solution (2.50 M hexane solution, 2.25 mL, 5.62 mmol) was gradually added. After stirring for 2.0 hours, tributyl chlorotin (1.82 g, 5.60 mmol) was added. The reaction mixture was then slowly warmed to room temperature and stirred overnight. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic phase was washed with MgSO 4 Dry and evaporate in vacuo to obtain compound 7 (3.06 g, 2.39 mmol).

[0137] (6) Synthesis of IR-FCD (Compound 8): The tin-containing product of Compound 7 (3.06 g, 2.39 mmol) and compound BBTD (benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole) (348 mg, 1 mmol) were combined in a 100 mL single-necked flask. Pd(PPh 3 ) 2 Cl 2 (150 mg), and then 40 mL of dry toluene solvent was added. The mixture was stirred at 130 ° C for 3 hours and then cooled to room temperature. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate. The crude product was purified by column chromatography using PE / DCM (2: 1) to obtain IR-FCD as a black solid (1.59 g, 73.4%). The H NMR spectrum of compound 8 ( 1 H NMR) Figure 7 As shown, the carbon spectrum ( 13 CNMR) Figure Figure 8 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.71(s,10H),7.35(s,8H),3.31(m,16H),2.05(m,20H),1.78–1.66(m,20H),1.35(m,20H),0.94–0.77(m,20H). 13C NMR(500MHz,Chloroform-d)δ173.39,152.15,150.55,145.47,140.64,139.30,138.95,135.88,131.18, 124.80,124.40,123.51,122.85,119.87,119.03,118.89,114.11,64.66,60.43,55.16,45.14,40.28,39. 44,39.04,38.17,36.55,35.01,34.47,34.41,34.32,34.04,32.75,32.65,31.96,31.90,31.54,30.34,30.16,29.74,29.40,29.36,29.31,29.23,29.07,27.97,27.78,24.52,23.57,22.73,14.17. HRMS (ESI) for C 98 H 115 N 4 Br 8 S 6 + ,([M+H + ]) Calculated value 2181.0767, measured value 2181.0805.

[0138] (7)IR-FCD-N 3 Synthesis of: Compound IR-FCD (100 mg, 0.046 mmol) and sodium azide (50 mg, 0.75 mmol) were dissolved in DMF (10 mL) and heated at 70 ° C for 3 hours. A large amount of water was then added until all solids were dissolved. The reactants were then extracted twice with ethyl acetate. The combined organic phases were washed with MgSO 4 The crude product was purified by silica gel flash column chromatography to obtain a dark brown solid IR-FCD-N 3 (72 mg, 83.4%) IR-FCD-N 3 The H NMR spectrum ( 1 H NMR) Fig. 9 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.53(d,J=8.6Hz,10H),7.26(s,2H),7.13(dd,J=8.6,2.4Hz,9H),3.26–3.09(m,16H),1.43(d,J=1.6Hz,41H),1.26(s,40H).

[0139] Example 2: Synthesis of LWTQT and LWTQT4P

[0140]

[0141] (1) Synthesis of LWTQT: The tin-containing product of (6-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-4,4-bis(6-bromohexyl)-4H-cyclopenta[2,1-b:3,4-b']dithiophen-2-yl)tributylstannane (Compound 1) (3.06 g, 2.39 mmol) and 4,9-dibromo-6,7-bis(5-(2-ethylhexyl)thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) (732 mg, 1 mmol) were mixed in a 100 mL single-necked flask. Pd(PPh 3 ) 2 Cl 2 (150 mg), and then 40 mL of dry toluene solvent was added. The mixture was stirred at 130 ° C for 3 hours and then cooled to room temperature. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous magnesium sulfate. The crude product was purified by column chromatography using PE / DCM (2: 1) to obtain LWTQT as a black solid (1.88 g, 73.4%). The H NMR spectrum of LWTQT ( 1 H NMR) Fig.10 As shown, the carbon spectrum ( 13 C NMR) Fig.11 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.74-7.69(m,6H),7.61(s,2H),7.53(d,2H),7.38-7.31(h,10H),6.82-6.81(d,2H),3.32-3.27(dt,16 H),2.95-2.94(d,4H),2.15-2.03(m,16H),1.78-1.64(ddt,18H),1.43-1.21(m,62H),0.90-0.85(m,12H). 13 C NMR (126 MHz, CDCl 3)δ158.06,151.07,150.47,149.19,147.10,145.48,145.30,140.71,139.33,138.97,138.48,134.27,131 .65,127.26,127.07,126.15,124.81,124.41,124.02,123.52,122.84,120.30,119.81,119.05,114.13,5 5.13,45.16,41.76,40.35,38.21,34.73,34.05,34.01,32.76,32.67,31.97,31.55,30.35,30.18,29.75,29.41,29.25,29.11,29.01,27.96,27.80,27.43,25.92,24.49,23.58,23.13,22.74,22.72,14.31,11.20.

[0142] (2)LWTQT-N 3 Synthesis of: Compound LWTQT (100 mg, 0.039 mmol) and sodium azide (50 mg, 0.75 mmol) were dissolved in DMF (10 mL) and heated at 70 °C for 3 hours. A large amount of water was then added until all the solids were dissolved. The reactants were then extracted twice with ethyl acetate. The combined organic phases were washed with MgSO 4 The crude product was purified by silica gel flash column chromatography to obtain a dark brown solid LWTQT-N 3 (72 mg, 81.8%) LWTQT-N 3 The H NMR spectrum ( 1 H NMR) Fig.12 shown. 1 H NMR(500MHz,CDCl3)δ9.05(s,1H),7.77–7.65(m,5H),7.59(s,2H),7.42–7.27(m,10H),7.10(dd,9.8Hz,2H),6.98(d,J=6 .4Hz,1H),6.81(s,1H),3.14(dt,6.9Hz,16H),2.96–2.87(m,4H),2.26–1.87(m,18H),1.44–1.35(m,38H),1.27(d,64H).

[0143] (3) Synthesis of LWTQT4P: LWTQT-N 3(72 mg) was dissolved in THF (5 mL) and copper (I) thiophene-2-carboxylate (CuTc) (5 mg), n-alkynyl-PEG-hydroxy PEG600 (using PEG600 as an example, Mn = 600) (93 mg), and tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) (3 mg) was added. The system was stirred at room temperature for 0.5 hours, then filtered through celite, and the solution was evaporated in vacuo. The crude product was purified twice by thin layer chromatography with DCM / MeOH (10:1) as the eluent to obtain LWTQT-4P (129 mg, 86%). The H NMR spectrum of LWTQT-4P ( 1 H NMR) Fig.13 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.74,-7.72(s,2H),7.50(s,10H),7.35(s,6H),4.66-4.63(d,2H),4.23(s,2H),3.66(s,192H ),3.39(s,12H),2.04(s,2H),1.81(s,6H),1.45(s,4H),1.27(s,12H),1.12(s,6H),0.60(s,4H).

[0144] Example 3: Synthesis of IR-BTOG

[0145]

[0146] (1) Synthesis of compound 2: Compound 2 was prepared according to the reference “Tian R, Ma H, Yang Q, et al. Rational design of a super-contrast NIR-II fluorophore affords high-performance NIR-II molecular imaging guided microsurgery[J]. Chemical science, 2019, 10(1): 326-332.”

[0147] (2) Synthesis of 2-(2,6-bis((6-bromohexyl)oxy)benzene)phenyl)thiophene (Compound 4): To a xylene (15 mL) solution of 2-bromo-1,3-bis((6-bromohexyl)oxy)benzene (Compound 2) (1.2 g, 2.33 mmol) and tri(thiophen-2-yl)stannane (Compound 3) (877 mg, 2.33 mmol) was added Pd(PPh3 ) 4 (269.2 mg, 0.233 mmol). The mixture was stirred at 130°C for 3 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 Dry and evaporate in vacuo. The crude product was purified by silica gel column chromatography to obtain compound 4 as a white solid (1.08 g, 89.2%). The H NMR spectrum of compound 4 ( 1 H NMR) Fig.14 As shown, the carbon spectrum ( 13 C NMR) Fig.15 As shown in the high resolution mass spectrometry (HRMS) Fig.16 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.40(d,J=3.5Hz,1H),7.29(d,J=5.1Hz,1H),7.10(s,1H),7.02(dd,J=13.3,9.3Hz,1H),6.54(d,J=8.3Hz,1H),6.45 (s,1H),3.95–3.92(m,4H),3.34(d,J=8.0Hz,4H),1.80(dd,J=14.3,7.1Hz,8H),1.48–1.46(m,4H),1.39–1.37(m,4H). 13 C NMR (126 MHz, CDCl 3 )δ157.12,156.73,133.98,128.70,128.46,128.04,125.63,125.05,113.02,105.77,105.34,102.17,77.29,77.04,76.79,74.15,69.06,68.79,68.58,33.90,33.87,32.70,32.66,28.97,28.95,27.87,27.79,25.32,25.27,13.63. HRMS (ESI) for C 22 H 31 O 2 Br 2 S 2 + ,([M+H + ]) Calculated value 519.0385, measured value 519.0372.

[0148] (3) Synthesis of 2-(2,6-bis((6-bromohexyl)oxy)phenyl)-5-bromothiophene (Compound 5): Under a nitrogen atmosphere, 1-bromopyrrolidine-2,5-dione (383.8 mg, 2.16 mmol) was added to a DMF (15 mL) solution of 2-(2,6-bis((6-bromohexyl)oxy)phenyl)thiophene (Compound 4) (1.12 g, 2.16 mmol). The mixture was stirred at -8°C for 1 hour. After the reaction was transferred to room temperature for 4 hours, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The crude product was dried and evaporated in vacuo. The crude product was purified by silica gel column chromatography to give 2-(2,6-bis((6-bromohexyl)oxy)phenyl)-5-bromothiophene (Compound 5) (1.01 g, 78.29%) as a light yellow oil.

[0149] (4) Synthesis of 5'-(2,6-bis((6-bromohexyl)oxy)phenyl)-3-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene (Compound 7): To a solution of Compound 5 (1 g, 1.67 mmol) and triphenyl(3-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)thiophen-2-yl)stannane (Compound 6) (896 mg, 1.67 mmol) in xylene (15 mL) was added Pd(PPh 3 ) 4 (193.49 mg, 0.167 mmol). The mixture was stirred at 130°C for 3 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The crude product was purified by silica gel column chromatography to obtain compound 7 (0.81 g, 63.9%) as a brown-black oil. 1 H NMR) Fig.17 As shown, the carbon spectrum ( 13 C NMR) Fig.18 As shown in the high resolution mass spectrometry (HRMS) Fig.19 shown. 1 H NMR (500 MHz, CDCl 3)δ7.34–7.20(m,2H),7.08(t,J=8.3Hz,1H),6.99–6.92(m,1H),6.80(t,J=4.8Hz,1H),6.53(d,J=3.7Hz,1H),4.21–4.17(m,2H),3.97–3.87(m,4H),3.82–3.78(m,2H),3.65(dd,J=5.8,3.7Hz,2H),3.58–3.53(m,4H),3.45–3.42(m,2H),3.30–3.25(m,7H),1.74(dd,J=8.8,7.0Hz,6H),1.39(dd,J=9.3,6.0Hz,6H),1.21–1.17(m,4H). 13 C NMR(126MHz,CDCl 3 )δ157.10,157.01,156.61,154.44,152.24,152.17,151.93,136.56,135.93,134.55,133.62,133.21,132.96,132.31,131.77,130.98,130.03,129.81,129.39,129.06,128.58,128.49,128.24,126.96,126.48,126.42,125.16,124.49,124.01,122.51,122.19,122.05,121.49,121.06,119.86,119.74,118.80,118.33,118.10,117.07,116.43,113.68,113.15,109.49,109.31,105.47,105.30,105.25,77.38,77.13,76.87,72.86,71.95,71.92,71.77,71.15,71.02,70.97,70.90,70.82,70.73,70.69,70.67,70.63,70.57,70.05,69.97,69.84,69.10,68.91,60.43,59.04,34.00,33.96,33.90,33.88,32.80,32.71,32.66,32.53,31.96,31.47,30.21,29.89,29.73,29.05,28.90,27.88,27.81,26.60,25.55,25.44,25.34,25.10,22.73,21.10,14.24,14.18.

[0150] (5) Synthesis of (5'-(2,6-bis((6-bromohexyl)oxy)phenyl)-3-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-[2,2'-bithiophen]-5-yl)tributylstannane (Compound 8): To a solution of Compound 7 (800 mg, 1.048 mmol) in THF (15.00 ml) was added dropwise n-BuLi solution (1.6 M hexane solution, 806 μL, 1.29 mmol) at -78 °C under nitrogen atmosphere. After the mixture was stirred at this temperature for another 2.0 hours, tributyltin chloride (420 mg, 1.29 mmol) was added to the solution. The reaction mixture was then slowly warmed to room temperature and stirred for 1.0 hour. The mixture was then poured into water and extracted twice with ethyl acetate, and the combined organic phases were washed with MgSO 4 Drying and evaporation in vacuo gave compound 8 without further purification.

[0151] (6) Synthesis of IR-BTOG: Pd(PPh 3 ) 2 Cl 2 (56.04 mg, 0.048 mmol). The mixture was stirred at 130°C for 10 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The crude product was purified by silica gel column chromatography to obtain IR-BTOG (320.46 mg, 69.75%) as a brown solid. 1 H NMR) Fig. 20 As shown, the carbon spectrum ( 13 C NMR) Fig.21 As shown in the high resolution mass spectrometry (HRMS) Fig. 22 shown. 1 HNMR (500MHz, CDCl 3)δ7.69(dd,J=12.0,7.1Hz,2H),7.58(dd,J=13.7,5.0Hz,2H),7.50(dd,J=7.7,2.7Hz,2H ),7.21(dd,J=8.3,3.5Hz,3H),6.65(dd,J=11.4,8.4Hz,3H),4.55(s,1H),4.33(s,1H),4 .03(ddd,J=47.7,27.1,18.6Hz,12H),3.82–3.51(m,18H),3.40(ddd,J=14.9,11.3,9.4H z,14H),1.88(d,J=6.6Hz,8H),1.53–1.47(m,8H),1.33–1.28(m,8H),0.92–0.85(m,8H). 13 C NMR (126 MHz, CDCl 3 )δ177.53,162.58,135.17,134.80,132.86,132.15,132.08,132.04,132.00,1 31.98,130.41,129.56,128.58,128.49,128.15,127.90,127.85,127.35,77.34 ,77.08,76.83,75.59,71.90,71.75,70.66,69.88,68.91,60.21,59.03,57.78,36.53,33.89,32.69,31.46,30.20,29.63,29.05,27.74,25.31.HRMS (ESI) for C 72 H 92 O 12 Br 4 N 4 S 6 + ,([M+H + ])Calculated value 1714.1577, measured value 1714.1681.

[0152] Example 4: Synthesis of IR-FEOG

[0153]

[0154] (1) Synthesis of compound 10: Compound 10 was prepared according to the reference “Yang Q, Z Ma, H Wang, B Zhou, S Zhu, Y Zhong, J Wang, H Wan, A Antaris, R Ma, X Zhang, J Yang, X Zhang, H Sun, W Liu, Y Liang, HDai, Rational Design of Molecular Fluorophores for Biological Imaging in the NIR-II Window, Adv Mater. 29(12)(2017)1605497. https: / / doi.org / 10.1002 / adma.201605497.”

[0155] (2) Synthesis of 5-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-7-bromo-2,3-dihydrothieno[3,4-b][1,4]dioxine (Compound 11): To a solution of 5-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-2,3-dihydrothieno[3,4-b][1,4]dioxine (Compound 10) (1 g, 1.58 mmol) in DMF (12 mL) was added 1-bromopyrrolidine-2,5-dione (281.4 mg, 1.58 mmol) under a nitrogen atmosphere. The mixture was stirred at -8°C for 1 hour. After the reaction was transferred to room temperature for 4 hours, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The residue was dried and evaporated in vacuo. The crude product was purified by silica gel column chromatography to give compound 11 (0.93 g, 83.0%) as a pale yellow oil.

[0156] (3) Synthesis of 5-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-7-(3-(2-(2-(2-methoxyethoxy)eth oxy)ethoxy)thiophen-2-yl)-2,3-dihydrothieno[3,4-b][1,4]dioxine (Compound 12): To a solution of Compound 11 (1.25 g, 1.76 mmol) and Compound 7 (945 mg, 1.76 mmol) in xylene (15 mL) was added Pd(PPh 3 ) 4(203.05 mg, 0.176 mmol). The mixture was stirred at 130°C for 3 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The crude product was purified by silica gel column chromatography to obtain compound 12 (0.87 g, 56.5%) as a brown-black oil. 1 H NMR) Fig.23 As shown, the carbon spectrum ( 13 C NMR) Fig.24 As shown in the high resolution mass spectrometry (HRMS) Fig.25 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.75–7.73(m,2H),7.37(dd,J=10.9,4.7Hz,2H),7.23–7.19(m,1H),7.11(dd,J=6.9,1.5Hz,1H),6.89– 6.85(m,2H),6.26(d,J=2.2Hz,1H),4.37–4.33(m,4H),4.27–4.23(m,4H),3.94–3.90(m,2H),3.78(dd,J= 7.2,3.1Hz,2H),3.68–3.64(m,4H),3.55–3.51(m,4H),3.36(d,J=1.9Hz,3H),2.34(s,2H),2.06–1.97(m, 2H),1.71–1.60(m,4H),1.48(dd,J=14.9,7.4Hz,4H),1.27(d,J=1.7Hz,2H),0.96(td,J=7.3,2.0Hz,6H). 13 C NMR (126 MHz, CDCl 3)δ152.39,152.19,141.11,137.73,137.04,136.57,133.32,128.60,126.23,125.89,122.41, 122.06,119.88,116.97,116.88,114.49,114.01,113.98,110.58,108.93,97.30,77.42,77.1 7,76.91,71.93,71.90,71.57,71.45,70.96,70.92,70.70,70.55,70.05,70.01,65.02,64.84,64.74,64.63,60.40,59.03,59.01,27.32,21.83,21.07,16.80,14.22,13.25.HRMS (ESI) for C 42 H 53 O 6 Br 2 S 2 + ,([M+H + ]) Calculated value 877.1624, measured value 877.1601.

[0157] (4) Synthesis of (5-(7-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)thiophen-2-yl)tributylstannane (Compound 13): To a solution of Compound 12 (622 mg, 0.71 mmol) in THF (10.00 ml) was added dropwise n-BuLi solution (1.6 M hexane solution, 530 μL, 0.85 mmol) at -78°C under nitrogen atmosphere. After the mixture was stirred at this temperature for another 2.0 hours, tributyltin chloride (267 μL, 0.85 mmol) was added to the solution. The reaction mixture was then slowly heated to room temperature and stirred for 1.0 hour. The mixture was then poured into water and extracted twice with ethyl acetate, and the combined organic phases were washed with MgSO 4 Drying and evaporation in vacuo gave compound 13.

[0158] (5) Synthesis of IR-FEOG: Pd(PPh 3 ) 2 Cl 2 (40.03 mg, 0.057 mmol). The mixture was stirred at 130°C for 10 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 Dry and evaporate in vacuo. The crude product was subjected to silica gel column chromatography to obtain IR-FEOG (216.49 mg, 58.6%) as a brown solid. The H NMR spectrum of IR-FEOG ( 1 H NMR) Fig.26 As shown, the carbon spectrum ( 13 C NMR) Fig. 27 As shown in the high resolution mass spectrometry (HRMS) Fig.28 shown. 1 HNMR (500MHz, CDCl 3 )δ7.83(s,2H),7.67(s,2H),7.64(s,2H),7.26(t,J=6.8Hz,8H),4.45(s,4H),4.32(s,4H),3.22(t,J=6.8Hz,8H ), 1.57 (dd, J = 15.6, 7.6 Hz, 22H), 1.27 ( d, J = 7.8 Hz, 22H), 1.01 ( dd, J = 17.3, 9.0 Hz, 22H), 0.84 ( d, J = 7.3 Hz, 22H). 13 C NMR (126 MHz, CDCl 3 )δ151.13,150.92,142.36,139.72,131.93,126.87,126.73,124.85,122.83,120.33,119.74,119.58,97.22,77.28,77.03,76.77,64.83,64.52,55.11,40.34,34.08,32.84,30.02,29.72,29.50,29.48,29.44,29.38,29.22,28.74,28.17,23.75. HRMS (ESI) for C 92 H 118 Br 4 O 4 N 4 S4 + ,([M+H + ])Calculated value 1940.2526, measured value 1940.2362.

[0159] Example 5: Synthesis of IR-FTOG

[0160]

[0161] (1) Synthesis of 2-bromo-9,9-bis(6-bromohexyl)-9H-fluorene (Compound 19): Compound 19 was prepared according to the reference “Yang Q, ZMa, HWang, BZhou, SZhu, YZhong, JWang, HWan, AAntaris, RMa, XZhang, JYang, XZhang, HSun, WLiu, YLiang, HDai, Rational Design of Molecular Fluorophores for Biological Imaging in the NIR-II Window, Adv Mater. 29(12)(2017)1605497. https: / / doi.org / 10.1002 / adma.201605497.”

[0162] (2) Synthesis of 2-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-5-bromothiophene (Compound 20): Under nitrogen atmosphere, 1-bromopyrrolidine-2,5-dione (309.83 mg, 1.74 mmol) was added to a DMF (15 mL) solution of Compound 19 (1 g, 1.74 mmol). The mixture was stirred at -8°C for 1 hour. After the mixture was transferred to room temperature for 4 hours, it was poured into water and extracted twice with ethyl acetate and MgSO 4 The residue was dried and evaporated in vacuo. The crude product was purified by silica gel column chromatography to give compound 20 (903 mg, 79.9%) as a pale yellow oil.

[0163] (3) Synthesis of 5'-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-3-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-2,2'-bithiophene (Compound 21): To a solution of Compound 20 (955 mg, 1.67 mmol) and Compound 7 (896 mg, 1.67 mmol) in xylene (15 mL) was added Pd(PPh 3 )4 (193.49 mg, 0.167 mmol). The mixture was stirred at 130°C for 3 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 The crude product was purified by silica gel column chromatography to obtain compound 21 (1.16 g, 84.7%) as a brown-black oil. 1 HNMR) Fig.29 As shown, the carbon spectrum ( 13 C NMR) Fig.30 As shown in the high resolution mass spectrometry (HRMS) Fig.31 shown. 1 H NMR (500 MHz, CDCl 3 )δ7.61(dd,J=7.0,4.8Hz,2H),7.54–7.42(m,3H),7.28–7.21(m,4H),7.08–6.97(m, 1H), 6.84 (t, J=6.8Hz, 1H), 4.24 (dd, J=10.2, 5.5Hz, 2H), 3.91–3.79 (m, 2H), 3.73–3. 66(m,2H),3.65–3.54(m,4H),3.49–3.42(m,2H),3.24–3.15(m,3H),1.93(t,J=8.1H z,4H),1.57(t,J=7.0Hz,4H),1.26(s,4H),1.10–0.99(m,4H),0.85(t,J=7.3Hz,4H). 13 C NMR (126 MHz, CDCl 3)δ152.37,151.62,151.12,150.69,150.46,147.27,142.64,142.14,140.72,140. 47,135.43,134.41,133.69,133.39,132.33,132.16,132.08,131.74,128.58,127. 50,127.17,126.99,125.06,124.59,124.07,123.32,123.00,122.78,122.50,121.58,120.46,120.14,119.98,119.74,119.53,118.88,118.16,116.70,116.48,111 .91,79.34,77.31,77.06,76.80,75.27,71.95,71.81,71.33,71.16,70.99,70.75,70.62,70.51,70.09,69.32,59.07,57.74,55.04,54.39,45.11,40.59,40.30,39. 32,34.01,33.68,32.65,32.47,32.07,31.46,31.19,30.21,29.73,29.07,28.70,27.78,27.56,26.83,26.62,26.49,26.09,23.55,15.46,13.64,0.92.HRMS (ESI) for C 40 H 51 O 4 Br 2 S 2 + ,([M+H + ]) Calculated value 819.1569, measured value 819.1561.

[0164] (4) Synthesis of (5'-(9,9-bis(6-bromohexyl)-9H-fluoren-2-yl)-3-(2-(2-(2-methoxyethoxy)ethoxy)-[2,2'-bithiophen]-5-yl)tributylstannane (Compound 22): To a solution of Compound 21 (665 mg, 8.12 mmol) in THF (15.00 ml) was added dropwise n-BuLi solution (1.6 M hexane solution, 806 μL, 1.29 mmol) at -78 °C under nitrogen atmosphere. After the mixture was stirred at this temperature for another 2.0 hours, tributyltin chloride (420 mg, 1.29 mmol) was added to the solution. The reaction mixture was then slowly warmed to room temperature and stirred for 1.0 hour. The mixture was then poured into water and extracted twice with ethyl acetate, and the combined organic phases were washed with MgSO 4 Drying and evaporation in vacuo gave compound 22.

[0165] (5) Synthesis of IR-FTOG (Compound 23): Under nitrogen atmosphere, Pd(PPh 3 ) 2 Cl 2 (40.03 mg, 0.057 mmol). The mixture was stirred at 130°C for 10 hours. After cooling to room temperature, the mixture was poured into water and extracted twice with ethyl acetate and MgSO 4 Dry and evaporate in vacuo. The crude product was purified by silica gel column chromatography to obtain IR-FTOG (210.49 mg, 60.57%). 1 H NMR) Fig.32 As shown, the carbon spectrum ( 13 C NMR) Fig.33 As shown in the high resolution mass spectrometry (HRMS) Fig.34 shown. 1 HNMR (500MHz, CDCl 3 )δ7.74–7.71(m,4H),7.62(d,J=7.0Hz,2H),7.40–7.32(m,12H),7.02(s,2H),4.40–4.37(m,3H),4.00–3.98(m,3H),3.84–

[0166] 3.82(m,3H),3.74(s,3H),3.69(s,3H),3.57(s,3H),3.39(s,6H),3.31–3.29(m ,6H),2.04(d,J=8.1Hz,10H),1.66(s,10H),1.22(s,10H),0.74–0.65(m,10H). 13 C NMR (126 MHz, CDCl 3 )δ177.22,168.27,157.60,157.50,157.11,156.58,152.61,152.51,151.92,142.00,135.18,1 35.02,134.55,134.15,133.39,131.80,130.41,129.19,129.06,128.49,128.24,127.90,127.2 3,126.97,126.91,126.42,125.34,124.67,122.96,122.17,121.60,121.47,121.41,121.05,120.85,119.62,119.18,118.80,118.44,118.33,115.41,113.18,106.73,105.48,99.33,97.51,8 6.51,77.34,77.08,76.83,74.21,71.93,71.51,71.15,71.11,70.90,70.84,70.79,70.68,70.66,70.58,70.19,70.04,69.97,69.70,69.57,68.91,61.68,59.06,57.14,45.08,44.06,38.80,3 5.19,33.96,33.73,32.70,32.53,31.67,31.46,31.04,30.21,30.15,29.59,29.04,28.33,28.18,27.87,27.06,26.84,26.74,26.59,26.01,25.54,25.43,20.00,13.64,-11.55. HRMS (ESI) for C 86 H 99 Br 4 O 8 N 4 S 6 + ,([M+H + ])Calculated value 1829.2453, measured value 1829.2541.

[0167] In addition, the present invention also tested the product IRFCD of Example 1 and the products LWTQT and LWTQT4P of Example 2. Fig.35 , 36 , LWTQT emission spectrum and quantum yield are shown in Fig.39 , LWTQT4P emission spectrum and quantum yield are shown in Fig.38 , IR-FCD emission spectrum and quantum yield are shown in Fig.37 .

[0168] The above embodiments are preferred implementation schemes of the present invention. In addition, the present invention may also be implemented in other ways. Any obvious replacement without departing from the concept of the present technical solution is within the protection scope of the present invention.

[0169] Finally, it should be emphasized that in order to allow ordinary technicians in the field to more easily understand the improvements of the present invention over the prior art, some descriptions of the present invention have been simplified, and for the sake of clarity, some other elements are omitted in this application document. Those skilled in the art should realize that these omitted elements may also constitute the content of the present invention.

Claims

1. A compound, characterized in that include: Electron acceptor aromatic unit, an optional electron donor aromatic unit, and a shielding unit, wherein the shielding unit shields the intermolecular interaction of the electron acceptor aromatic unit and / or the electron donor aromatic unit, wherein the electron acceptor aromatic unit, the electron donor aromatic unit and the shielding unit are connected by covalent bonds, The electron acceptor aromatic unit has a formula selected from any one of the group consisting of: Each of Z1, Z2, Z3 and Z4 is independently O, S, Se or N, Ti, Each R is independently H, C n1 H 2n1+1 or tert-butyloxycarbonyl, Each n1 is independently an integer in the range of 1 to 12, The electron donor aromatic unit has a formula selected from any one of the group consisting of: Each Z1 is independently O, S, Se or N, Ti, Each of P1 and P2 is independently H, OC n2 H 2n2+1 , C n2 H 2n2+1 , OC n2 H 2n2 B or C n2 H 2n2 Z, Each R1 is independently H, C n1 H 2n1+1 or PEG, alkoxy, Each X is independently S, Se, NR1 or O, Each of Y1 and Y2 is independently H, OC n2 H 2n2+1 , C n2 H 2n2+1 , OC n2 H 2n2 B or C n2 H 2n2 Z, each B is independently Br, I, OTs, OMs, ONs, N3 or Ome, Each Z is independently Br or N3, Each m is independently an integer ranging from 0 to 6, Each N2 is independently an integer in the range of 1 to 20, Each p is independently an integer ranging from 1 to 20, The shielding unit has a formula selected from any one of the group consisting of: Each R2 is independently -(CH2) n3 W, Each W is independently H, Br, I, OH, Ots, N3, each Z5 is independently S, Se, O or N, Each X1 is independently Si, Ge or C, Each n3 is independently an integer in the range of 1 to 20, Each n is independently an integer ranging from 4 to 120, Each b is independently an integer ranging from 1 to 6.

2. The compound according to claim 1, characterized in that: The compound comprises two shielding units and two electron donor aromatic units, and the compound has a formula of S'1-D1-A-D2-S'2, wherein S'1 represents the first shielding unit, S'2 represents the second shielding unit, D1 represents the first electron donor aromatic unit, D2 represents the second electron donor aromatic unit, A represents an electron acceptor aromatic unit.

3. The compound according to claim 1, characterized in that: The compound has the formula S'-DA, wherein S' represents the shielding unit, D represents an electron donor aromatic unit, A represents an electron acceptor aromatic unit.

4. The compound according to claim 1, characterized in that: The compound comprises two electron acceptor aromatic units, three electron donor aromatic units and two shielding units, and the compound has a formula of S'3-D3-A1-D5-A2-D4-S'4, wherein S'3 represents the third shielding unit, S'4 represents the fourth shielding unit, D3 represents the third electron donor aromatic unit, D4 represents the fourth electron donor aromatic unit, D5 represents the fifth electron donor aromatic unit, A1 represents the first electron acceptor aromatic unit, A2 represents a second electron acceptor aromatic unit.

5. The compound according to claim 1, characterized in that The compound has a formula selected from any one of the group consisting of: Each of X, Y, Z1, Z2, Z3, Z4 and Z5 is independently O, S, Se or N, Each X1 is independently Si, Ge or C, Each of Y1, Y2 and R8 is independently C n2 H 2n2+1 , OC n2 H 2n2+1、 OC n2 H 2n2 B. each B is independently Br, I, OTs, OMs, ONs, N3 or OMe, Each R2 is independently -(CH2) n3 W1, Each W1 is independently N3, Each R4 is independently -(CH2) n3 W2, Each W2 is independently N3, Each R6 is independently -(CH2) n3 W3, Each W3 is independently H, N3, Each n2 is independently an integer in the range of 2 to 20, Each n3 is independently an integer in the range of 2 to 20, Each p is independently an integer ranging from 1 to 20, Each n is independently an integer ranging from 4 to 120, Each b is independently an integer ranging from 1 to 6.

6. The compound according to claim 1, characterized in that The compound has a formula selected from any one of the group consisting of: Among them, each wherein n is independently an integer ranging from 1 to 100.

7. A kit, characterized in that: The invention comprises the compound according to any one of claims 1 to 6.

8. Use of the compound according to any one of claims 1 to 6 or the kit according to claim 7 in non-disease diagnosis biomedical imaging or labeling of biomacromolecules.

9. A method for biomedical imaging for non-disease diagnosis, characterized in that: include: The compound according to any one of claims 1 to 6 or the kit according to claim 7 is administered to an organism or a tissue.

10. A method for labeling biomacromolecules, characterized in that: include: The compound according to any one of claims 1 to 6 or the kit according to claim 7 is reacted with the biomacromolecule.

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