Compound, preparation method and application thereof, and preparation method of near-infrared-IIa fluorescence imaging contrast agent

Abstract

The present invention relates to a compound and a preparation method and application thereof, and a preparation method of a near-infrared-IIa fluorescent imaging contrast agent, and belongs to the field of nano-biomedical imaging technology. The compound as shown in formula I of the present invention is a D-A-D type organic small molecule with a bithiophene benzothiadiazole group as an electron acceptor and a thiophene group as an electron donor, and the electron acceptor bithiophene benzothiadiazole with a twisted configuration is conducive to the formation of a TICT state, so that the compound has a twisted intramolecular charge transfer characteristic (TICT), can be excited by a near-infrared-IIa (1064) light source, and has an emission wavelength range of 950-1400nm, achieving a better fluorescence imaging effect.

Description

Technical Field

[0001] The invention relates to a compound and a preparation method and application thereof, and a preparation method of a near-infrared-IIa fluorescent imaging contrast agent, belonging to the technical field of nano-biomedical imaging. Background Art

[0002] Near-infrared II (1000-1700 nm) fluorescence imaging technology, especially near-infrared IIa (1300-1400 nm) fluorescence imaging excited by near-infrared II light sources, has gradually become a rising star in the field of nanobiomedical imaging technology due to its deeper tissue penetration, higher imaging resolution and greater maximum allowable exposure density compared to traditional fluorescence imaging technology (wavelength less than 900 nm). At present, several classic inorganic / organic contrast agents excited by near-infrared II light sources have been developed for near-infrared IIa fluorescence imaging. Among them, organic molecules without heavy metal toxicity, including conjugated polymers and some small molecules, are more promising in clinical transformation. However, conjugated polymers usually encounter problems such as poor biodegradability, low synthetic reproducibility and poor fluorescence performance. For traditional small molecules, such as polymethine cyanine dyes, poor photostability and low photothermal efficiency are the main factors restricting their further application. Therefore, it is very necessary to develop ideal near-infrared IIa organic dyes with excellent optical properties that can be excited by near-infrared II light.

[0003] With clear chemical structure, reliable biodegradability / biocompatibility and flexible optical properties, donor-acceptor-donor (DAD) type conjugated small molecules have great potential to construct near-infrared IIa fluorescent contrast agents excited by near-infrared II light. So far, several effective strategies have been proposed, including heteroatom replacement, enhancing electronic D / A intensity and extending the length of the conjugated skeleton, to shift the absorption wavelength into the near-infrared II window, thereby achieving near-infrared II light excitation. However, due to the limitation of intramolecular charge transfer (ICT), the absorption and emission wavelengths of fluorescent molecules are short. The emission wavelengths of these compounds, such as cyanines, BODIPYs and some conjugated polymers, are concentrated in 1000-1100 nanometers, which are easily affected by the spectral absorption of living tissues and background fluorescence, have poor penetration ability, and the fluorescence imaging effect is difficult to meet the requirements. Summary of the invention

[0004] The object of the present invention is to provide a compound capable of realizing near-infrared second-region light excitation and having a longer emission wavelength.

[0005] The present invention also provides a preparation method and application of the above compound, and also provides a preparation method of a near-infrared II-a fluorescent imaging contrast agent.

[0006] In order to achieve the above purpose, the technical solution adopted by the compound of the present invention is:

[0007] A compound as shown in formula I:

[0008]

[0009] In formula I, R1 is hydrogen or a C1-C30 alkyl group; R2 is a group represented by formula II or formula III;

[0010]

[0011] In formula II, n is 1, 2 or 3, and R3 and R4 are independently selected from hydrogen or C1-C10 alkyl;

[0012] In formula III, R4 is hydrogen or a C1-C10 alkyl group.

[0013] The compound shown in Formula I of the present invention is a DAD-type organic small molecule with a bithiophene benzothiadiazole group as an electron acceptor and a thiophene group as an electron donor. The electron acceptor bithiophene benzothiadiazole group with a twisted configuration is conducive to the formation of a TICT state, so that the compound has a twisted intramolecular charge transfer characteristic (TICT), can be excited by a near-infrared-IIa (1064nm) light source, and emits fluorescence with a wavelength of 950-1400nm, achieving a better fluorescence imaging effect. By changing the number of electron donor thiophene groups in the R2 group, modifying the rigid alkyl chain of the terminal group, or introducing a large sterically hindered ethylenedioxythiophene group, the TICT intensity of this type of near-infrared II-a fluorescent small molecule can be regulated.

[0014] Further, R1 is hydrogen or a C15-C25 alkyl group, for example, a C20 alkyl group. Connecting an alkyl group to the thiophene group can effectively solve the solubility of the conjugated polymer after coupling polymerization, and at the same time can improve the reactivity of the thiophene tin reagent. Further, in Formula I, R1 is hydrogen or -CH2CH(R5)R6, R5 is a C8-C13 alkyl group, and R6 is a C6-C11 alkyl group, for example, R5 is a C10 alkyl group, and R6 is a C8 alkyl group. In Formula II, R3 is hydrogen or a C4-C8 alkyl group, for example, a C6 alkyl group. In Formula III, R4 is a C4-C8 alkyl group, for example, a C6 alkyl group.

[0015] In formula I, R1 is -CH2CH(R5)R6, R5 is a C10 straight chain alkyl (i.e., -(CH2)9CH3 straight chain alkyl), and R6 is a C8 straight chain alkyl (i.e., -(CH2)7CH3 straight chain alkyl); in formula II, R3 is hydrogen or a C6 straight chain alkyl (i.e., -(CH2)5CH3 straight chain alkyl); in formula III, R4 is a C6 straight chain alkyl (i.e., -(CH2)5CH3 straight chain alkyl).

[0016] The technical solution adopted by the method for preparing the compound represented by formula I of the present invention is:

[0017] A method for preparing the compound of formula I comprises the following steps: subjecting the compound of formula IV to a Stille coupling reaction with the compound of formula V or formula VI in an organic solvent to generate the compound of formula I;

[0018]

[0019] In formula IV, R1 is hydrogen or C1-C30 alkyl, and X is a halo group;

[0020] In formula V, n is 1, 2 or 3, and R3 is hydrogen or a C1-C10 alkyl group;

[0021] In formula VI, R4 is hydrogen or a C1-C10 alkyl group.

[0022] The method for preparing the compound represented by formula I of the present invention has a simple process and can obtain the compound represented by formula I in a one-step reaction.

[0023] Further, the temperature of the Stille coupling reaction is 90 to 110° C., for example, 100° C., and the time is 12 to 24 hours, for example, 24 hours; the Stille coupling reaction is carried out under the action of a palladium catalyst. The palladium catalyst is a tetrakis(triphenylphosphine)palladium catalyst. The Stille coupling reaction is carried out in an oxygen-free, anhydrous environment. The organic solvent is dehydrated and / or deoxygenated before use, for example, nitrogen or argon is introduced into the organic solvent for bubbling treatment to remove oxygen. The organic solvent is anhydrous toluene. Anhydrous toluene is deoxygenated before use. Further, in formula IV, X is preferably -Cl, -Br or -I. The molar ratio of the compound shown in formula IV to the compound shown in formula V or formula VI is ≤1:2, for example, 1:3.

[0024] Further, in Formula IV, R1 is hydrogen or -CH2CH(R5)R6, R5 is a C8-C13 alkyl group, and R6 is a C6-C11 alkyl group, for example, R5 is a C10 alkyl group, and R6 is a C8 alkyl group. In Formula V, R3 is hydrogen or a C4-C8 alkyl group, for example, a C6 alkyl group. In Formula VI, R4 is a C4-C8 alkyl group, for example, a C6 alkyl group.

[0025] In formula IV, R1 is -CH2CH(R5)R6, R5 is a C10 straight chain alkyl (i.e., -(CH2)9CH3 straight chain alkyl), and R6 is a C8 straight chain alkyl (i.e., -(CH2)7CH3 straight chain alkyl); in formula V, R3 is hydrogen or a C6 straight chain alkyl (i.e., -(CH2)5CH3 straight chain alkyl); in formula VI, R4 is a C6 straight chain alkyl (i.e., -(CH2)5CH3 straight chain alkyl).

[0026] Furthermore, the preparation method of the compound shown in the above formula I also includes the following steps: after the Stille coupling reaction is completed, an organic solvent is added to the system to dissolve the reaction product, solid-liquid separation is performed, silica gel powder is added to the resulting liquid to adsorb the reaction product, the silica gel powder is loaded into a column, and then eluted with an eluent by silica gel column chromatography, the reaction product solution is collected, and the solvent is removed. The particle size of the silica gel powder is 200 mesh, the organic solvent added to the system is dichloromethane, and the eluent is a mixture of dichloromethane and methanol.

[0027] The technical solution adopted in the application of the compound represented by formula I of the present invention is:

[0028] The invention discloses an application of a compound of formula I in fluorescence imaging or in the preparation of a fluorescence imaging contrast agent. The compound of formula I of the present invention is used for fluorescence imaging for non-disease diagnosis and treatment purposes by utilizing the absorption extending to the near-infrared region II and the unique near-infrared-IIa emission peak (the TICT emission peak is red-shifted to the near-infrared-IIa window with almost zero background noise), and can be used for high-resolution near-infrared-IIa fluorescence imaging excited in the near-infrared region II. The compound of formula I of the present invention can be used as a cell contrast agent and intracellular substance probe, such as for organelle positioning, intracellular environment detection, etc.

[0029] The technical solution adopted by the preparation method of the near-infrared-IIa fluorescent imaging contrast agent of the present invention is:

[0030] A method for preparing a near-infrared-IIa fluorescent imaging contrast agent comprises the following steps: mixing an organic solution of a compound represented by formula I and an aqueous solution of an amphiphilic block copolymer under ultrasonic conditions, and removing an organic solvent from the organic solution after completing self-assembly of the compound and the amphiphilic block polymer.

[0031] The preparation method of the near-infrared-IIa fluorescent imaging contrast agent of the present invention is to prepare a TICT-type water-soluble near-infrared-IIa fluorescent imaging contrast agent by self-assembling a near-infrared-IIa small molecule with controllable TICT properties and an amphiphilic block polymer in a solution. The preparation method of the near-infrared-IIa fluorescent imaging contrast agent of the present invention is simple, and the prepared near-infrared-IIa fluorescent imaging contrast agent can be excited by a near-infrared second-zone light source, and realizes fluorescent imaging in the near-infrared-IIa window, thereby greatly improving the imaging quality of living blood vessels and tumors. Experiments show that the near-infrared-IIa fluorescent imaging contrast agent prepared by the present invention can realize high-resolution NIR-IIa fluorescent imaging of living blood vessels and tumors of mice by near-infrared second-zone excitation.

[0032] Further, the mass ratio of the compound shown in formula I to the amphiphilic block copolymer is 1:5 to 100, for example, 1:20. By self-assembling the amphiphilic block copolymer with the compound of formula I, the water solubility of the compound of formula I can be achieved, and the nanostructure formed by self-assembly has good biocompatibility. Further, the amphiphilic block copolymer is an amphiphilic triblock copolymer. Further, the amphiphilic block copolymer is an amphiphilic triblock polymer F-127. The compound shown in formula I of the present invention (fluorescent imaging small molecule) and the amphiphilic triblock polymer F-127 are self-assembled in a solution, and the obtained water-soluble near-infrared-IIa fluorescent imaging contrast agent has significant TICT characteristics.

[0033] It can be understood that the organic good solvents of the compound shown in formula I can all be used as solvents for organic solvents. Furthermore, the organic solvent used in the organic solution is tetrahydrofuran. The concentration of the compound shown in formula I in the organic solution is 0.1-1 mg / mL, for example, 0.1-0.5 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1-20 mg / mL, for example, 1-2 mg / mL. The volume ratio of the organic solution to the amphiphilic front polymer aqueous solution is ≤1:5. The organic solvent from the organic solution can be removed by blowing volatilization method. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the compounds prepared in Examples 8 to 10 of the present invention;

[0035] Figure 2 The time-of-flight mass spectra of the compounds prepared in Examples 8 to 10 of the present invention;

[0036] Figure 3 is the hydrogen nuclear magnetic resonance spectrum of the compounds prepared in Examples 11 to 13 of the present invention;

[0037] Figure 4 is a time-of-flight mass spectrum of the compounds prepared in Examples 11 to 13 of the present invention;

[0038] Figure 5 is the hydrogen nuclear magnetic resonance spectrum of the compound prepared in Example 14 of the present invention;

[0039] Figure 6 is a time-of-flight mass spectrum of the compound prepared in Example 14 of the present invention;

[0040] Figure 7 This is a transmission electron microscope photograph of a contrast agent solution prepared by the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 16 in Experimental Example 1 of the present invention;

[0041] Figure 8This is a transmission electron microscope photograph of a contrast agent solution prepared by the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 19 in Experimental Example 1 of the present invention;

[0042] Fig. 9 This is a transmission electron microscope photograph of a contrast agent solution prepared by the near-infrared II-a fluorescent imaging contrast agent prepared in Example 21 in Experimental Example 1 of the present invention;

[0043] Fig.10 Schematic diagram of the hydrodynamic diameter measured by dynamic light scattering of the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 16 of the present invention;

[0044] Fig.11 Schematic diagram of the hydrodynamic diameter measured by dynamic light scattering of the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 19 of the present invention;

[0045] Fig.12 Schematic diagram of the hydrodynamic diameter measured by dynamic light scattering of the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 21 of the present invention;

[0046] Fig.13 Absorption spectra of aqueous solutions of contrast agents prepared for the near-infrared-IIa fluorescent imaging contrast agents prepared in Examples 16, 19 and 21 of the present invention;

[0047] Fig.14 The fluorescence emission spectrum of the contrast agent aqueous solution prepared by the near-infrared-IIa fluorescence imaging contrast agent prepared in Example 16, Example 19, and Example 21 of the present invention;

[0048] Fig.15 The emission spectrum of the near-infrared-IIa fluorescent imaging contrast agent prepared in Example 16, Example 19 and Example 21 of the present invention under 1064 nm laser excitation;

[0049] Fig.16 This is the mouse vascular imaging image of the contrast agent aqueous solution in Experimental Example 2;

[0050] Fig.17 This is the mouse tumor imaging image of the contrast agent aqueous solution in Experimental Example 2. DETAILED DESCRIPTION

[0051] The technical solution of the present invention is further described below in conjunction with specific implementation methods.

[0052] Example 1

[0053] The compound shown in Formula I in this embodiment is:

[0054]

[0055] Example 2

[0056] The compound shown in Formula I in this embodiment is:

[0057]

[0058] Example 3

[0059] The compound shown in Formula I in this embodiment is:

[0060]

[0061] Example 4

[0062] The compound shown in Formula I in this embodiment is:

[0063]

[0064] Example 5

[0065] The compound shown in Formula I in this embodiment is:

[0066]

[0067] Example 6

[0068] The compound shown in Formula I in this embodiment is:

[0069]

[0070] Example 7

[0071] The compound shown in Formula I in this embodiment is:

[0072]

[0073] Example 8

[0074] This embodiment is a method for preparing the compound shown in Formula I in Example 1, comprising the following steps:

[0075] In a 50mL flask, add 0.1mmol of a dithiophene benzothiadiazole compound as shown in formula VII, 0.3mmol of a compound as shown in formula VIII, and 0.0006mmol of a catalyst tetrakis(triphenylphosphine)palladium, connect a reflux tube, evacuate the entire system and fill it with nitrogen under light-proof conditions, then add anhydrous toluene that has been bubbling (the gas introduced is nitrogen) to the flask and stir at 100°C for 24h. After the reaction is completed, add dichloromethane to dissolve the reaction product, filter and remove insoluble matter to obtain a crude product solution, add 50g of silica gel powder (200 mesh), and remove all solvents by rotary evaporation to allow the silica gel powder to fully adsorb the crude product. After the silica gel powder adsorbing the crude product is loaded on a column, a silica gel column chromatography separation method is used, and a dichloromethane / methanol mixed solution is used for elution to obtain a pure product solution. After rotary evaporation to remove the solvent, vacuum drying is performed to obtain a TICT type near-infrared-IIa fluorescent small molecule final product. The synthetic route is:

[0076]

[0077] In the bithiophene benzothiadiazole compound represented by formula VII of this embodiment, the alkyl-C 10 H 21 and -C8H 17 All are straight chain alkyl groups, alkyl-C 10 H 21 The structure is -(CH2)9CH3, alkyl -C8H 17 The structure of is -(CH2)7CH3.

[0078] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 1 (a), time-of-flight mass spectrometry Figure 2 (a) shown.

[0079] Example 9

[0080] This example is a method for preparing the compound of formula I of example 2, which differs from the method of example 8 only in that the compound of formula VIII in example 8 is replaced by the compound of formula IX. The synthetic route is:

[0081]

[0082] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 1 (b), time-of-flight mass spectrometry Figure 2 (b) as shown.

[0083] Example 10

[0084] This embodiment is a method for preparing the compound of formula I of embodiment 3, which differs from the method for preparing embodiment 8 only in that the compound of formula VIII in embodiment 8 is replaced by a compound of formula X. The synthetic route is:

[0085]

[0086] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 1 (c), time-of-flight mass spectrometry Figure 2 (c) as shown.

[0087] Embodiment 11

[0088] This embodiment is a method for preparing the compound of formula I of embodiment 4, comprising the following steps: The difference from the preparation method of embodiment 8 is that the compound of formula VIII in embodiment 8 is replaced by a compound of formula XI (the alkyl-C6H 13 It is a straight chain alkyl with a structure of -(CH2)5CH3), and the synthesis route is:

[0089]

[0090] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 3 (a), time-of-flight mass spectrometry Figure 4 (a) shown.

[0091] Example 12

[0092] This embodiment is a method for preparing the compound of formula I of embodiment 5, which is different from the method for preparing embodiment 8 in that the compound of formula VIII in embodiment 8 is replaced by a compound of formula XII (the alkyl-C6H 13 It is a straight chain alkyl with a structure of -(CH2)5CH3), and the synthesis route is:

[0093]

[0094] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 3 (b), time-of-flight mass spectrometry Figure 4 (b) as shown.

[0095] Embodiment 13

[0096] This embodiment is a method for preparing the compound of formula I of embodiment 6, which is different from the method for preparing embodiment 8 in that the compound of formula VIII in embodiment 8 is replaced by a compound of formula XIII (the alkyl-C6H 13It is a straight chain alkyl with a structure of -(CH2)5CH3), and the synthesis route is:

[0097]

[0098] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 3 (c), time-of-flight mass spectrometry Figure 4 (c) as shown.

[0099] Embodiment 14

[0100] This embodiment is a method for preparing the compound of formula I of embodiment 7, which is different from the method for preparing embodiment 8 in that the compound of formula VIII in embodiment 8 is replaced by a compound of formula XIV (the alkyl-C6H 13 It is a straight chain alkyl with a structure of -(CH2)5CH3), and the synthesis route is:

[0101]

[0102] The hydrogen nuclear magnetic resonance spectrum of the compound prepared in this example is as follows Figure 5 , the time-of-flight mass spectrum is as follows Figure 6 shown.

[0103] Examples 15 to 21

[0104] The preparation method of the near-infrared-IIa fluorescent imaging contrast agent of Example 15 to Example 21 comprises the following steps:

[0105] The tetrahydrofuran solution of the compound of formula I (referred to as solution A) is directly added to the aqueous solution of the amphiphilic triblock polymer F-127 (referred to as solution B) under severe ultrasonic conditions for mixing, and after self-assembly is completed under ultrasonic conditions, the excess tetrahydrofuran organic solvent is removed by blowing and volatilization to obtain a near-infrared-IIa fluorescent imaging contrast agent; the volume ratio of solution A to solution B is 1:5. The concentrations of the compound of formula I used in the preparation methods of Examples 15 to 21, the compound of formula I in solution A, and the concentration of the amphiphilic triblock polymer F-127 in solution B are shown in Table 1.

[0106] Table 1 Compounds of Formula I used in Examples 15 to 21, concentrations of compounds of Formula I in Solution A, and concentrations of amphiphilic three-stage polymer F-127 in Solution B

[0107]

[0108] Experimental Example 1

[0109] The near-infrared-IIa fluorescent imaging contrast agents prepared in Example 16, Example 19 and Example 21 were respectively formulated into aqueous solutions of the contrast agent having a concentration of 0.01 mg / mL of the compound of formula I.

[0110] 1) Test each contrast agent aqueous solution using transmission electron microscopy to obtain transmission electron microscopy images (see Figures 7 to 9 ) and the particle size of the nanoparticles in the contrast agent of each embodiment. The results are shown in Table 2.

[0111] Table 2 Particle size of nanoparticles in contrast agents prepared in Example 16, Example 19 and Example 21

[0112] Particle size of nanoparticles in contrast agents (nm) Example 16 30～80 Embodiment 19 40～90 Embodiment 21 40～100

[0113] 2) Determine the hydrodynamic radius of each contrast agent aqueous solution based on dynamic light scattering, such as Figures 10-12 As shown in the figure, it can be seen that the fluid dynamics radius of the near-infrared-IIa fluorescent imaging contrast agents prepared in Example 16, Example 19 and Example 21 are 60nm, 88nm and 90nm respectively.

[0114] 3) Determine the absorption and fluorescence emission spectra of each contrast agent aqueous solution, such as Fig.13 and Fig.14 shown.

[0115] Depend on Fig.13 and 14 It can be seen that their near-infrared absorption peak is around 900 nanometers, and there is still good absorption at 1064 nanometers, while the emission spectrum shows two obvious main peaks, around 1100 and 1300 nanometers, which are obviously near-infrared-IIa emitting materials.

[0116] 4) Determine the emission spectra of each contrast agent aqueous solution under 1064 nm laser excitation, such as Fig.15 shown.

[0117] Depend on Fig.15 It can be seen that the emission peak is in the 1275 nanometer band and the emission band extends to the near-infrared-IIa window, which is obviously a material that can be excited by near-infrared II light source.

[0118] Experimental Example 2

[0119] The near-infrared-IIa fluorescent imaging contrast agent prepared in Example 21 was formulated into an aqueous solution of the contrast agent having a concentration of 0.15 mg / mL of the compound of formula I.

[0120] 1) Select mice bearing mouse breast cancer cells, inject 150 microliters of the prepared contrast agent aqueous solution into the tail vein, and use a near-infrared zone 2 imager to perform local (brain, abdomen and leg) vascular imaging of the mice (the light source is a laser with a wavelength of 1064nm). The vascular imaging is shown in the figure below. Fig.16 As shown, the main blood vessels and branch blood vessels in the imaging area are clearly distinguished from the surrounding background tissues, showing high-resolution near-infrared-IIa fluorescence imaging using small molecule seven contrast agents.

[0121] 2) Tumor-bearing mice carrying mouse breast cancer cells were selected, and 150 μl of the prepared contrast agent aqueous solution was injected into the tail vein. The tumors of the mice were imaged at different time points using a near-infrared zone 2 imager (the light source was a laser with a wavelength of 1064 nm). The tumor imaging images are shown in the figure below. Fig.17 As shown in the figure, it can be seen that 8-24 hours after tail vein injection, the contrast agent is significantly enriched in the tumor site (dashed circle), and the fluorescence intensity of the second zone is significantly higher than that of the surrounding tissue, proving that it can image cancer lesions.

Claims

1. A compound as shown in formula I: In Formula I, R1 is -CH2CH(R5)R6, R5 is a C8-C13 alkyl group, R6 is a C6-C11 alkyl group, and R2 is a group represented by Formula II or Formula III; In formula II, n is 1, 2 or 3, and R3 is hydrogen or a C1-C10 alkyl group; In formula III, R4 is hydrogen or a C1-C10 alkyl group.

2. The compound according to claim 1, characterized in that: In formula II, R3 is hydrogen or C4-C8 alkyl; in formula III, R4 is C4-C8 alkyl.

3. The compound according to claim 1 or 2, characterized in that: R1 is -CH2CH(R5)R6, R5 is a C10 straight-chain alkyl, and R6 is a C8 straight-chain alkyl; in formula II, R3 is hydrogen or a C6 straight-chain alkyl; in formula III, R4 is a C6 straight-chain alkyl.

4. A method for preparing a compound according to any one of claims 1 to 3, characterized in that: The following steps are involved: The compound represented by Formula IV and the compound represented by Formula V or Formula VI are subjected to Stille coupling reaction in an organic solvent to generate a compound represented by Formula I; In formula IV, R1 is -CH2CH(R5)R6, R5 is a C8-C13 alkyl group, R6 is a C6-C11 alkyl group, and X is a halo group; In formula V, n is 1, 2 or 3, and R3 is hydrogen or a C1-C10 alkyl group; In formula VI, R4 is hydrogen or a C1-C10 alkyl group.

5. The method for preparing the compound according to claim 4, characterized in that: The temperature of the Stille coupling reaction is 90-110° C. and the time is 12-24 hours; the Stille coupling reaction is carried out under the action of a palladium catalyst.

6. The method for preparing the compound according to claim 4, characterized in that: The Stille coupling reaction is carried out in an oxygen-free environment; in formula IV, X is -Cl, -Br or -I; the molar ratio of the compound represented by formula IV to the compound represented by formula V or formula VI is ≤1:

2.

7. Use of the compound according to any one of claims 1 to 3 in fluorescence imaging or in the preparation of fluorescence imaging contrast agents.

8. A method for preparing a near-infrared-IIa fluorescent imaging contrast agent, characterized in that: The following steps are involved: The organic solution of the compound represented by formula I as claimed in any one of claims 1 to 3 and the aqueous solution of the amphiphilic block copolymer are mixed under ultrasonic conditions, and the organic solvent from the organic solution is removed after the self-assembly of the compound and the amphiphilic block polymer is completed.

9. The method for preparing the fluorescent imaging contrast agent according to claim 8, characterized in that: The mass ratio of the compound represented by formula I to the amphiphilic block copolymer is 1:5-100; the amphiphilic block copolymer is an amphiphilic triblock copolymer.

10. The method for preparing the fluorescent imaging contrast agent according to claim 8 or 9, characterized in that: The concentration of the compound represented by formula I in the organic solution is 0.1-1 mg / mL, and the concentration of the amphiphilic block polymer aqueous solution is 1-20 mg / mL.

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