Para-substituted heptamethine quinone cyanine dye as well as synthesis method and application thereof

Abstract

The invention discloses a para-substituted heptamethine quinone cyanine dye as well as a synthesis method and application thereof, the structural general formula of the para-substituted heptamethine quinone cyanine dye is shown as I, that is, by introducing a specific quinone structure and a substituent group, the near-infrared light absorption and triplet excited state generation capability is optimized. The dye efficiently absorbs light within the wavelength range of 600-700 nanometers, the intersystem crossing efficiency is remarkably improved, and the photo-initiation effect is enhanced. According to the dye, heavy atoms are not used, and the solubility and the environmental protection property are improved. The synthesis method is simple, low in cost, mild in condition and suitable for large-scale production. The key steps comprise formation of quaternary ammonium salt, preparation of a condensing agent and synthesis of a final product, and parameters of each step are optimized to ensure high yield. The dye is suitable for photodynamic therapy, photoinitiation of photopolymerization materials, biological imaging and the like, and has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of near-infrared photoinitiator synthesis, and in particular to a class of para-substituted heptamethine quinone cyanine dyes and a synthesis method and application thereof. Background Art

[0002] Photopolymerization technology is considered to be an environmentally friendly, precise, safe and efficient method for constructing macromolecular materials. Therefore, this technology has been widely used in fields such as additive manufacturing and photoresist. Photoinitiator (PI), as a key component of the photopolymerization system, is crucial to determining the rate and extent of photopolymerization and the properties of the resulting material. According to the emission wavelength of the absorbed radiation light source, photoinitiators can be divided into ultraviolet (UV), visible light (Vis) and near infrared (NIR) types, among which UV type is the most widely used type today.

[0003] However, UV-type PIs face limitations due to the disadvantages of UV sources, such as high energy consumption, short life, and ozone release. In contrast, NIR-type PIs show a trend of replacing UV-types due to the specific characteristics provided by NIR light sources. Therefore, NIR photoinitiators have received great attention in recent years, and the design and development of dye molecules with near-infrared absorption properties and high-efficiency photoinitiation has become a difficult problem that needs to be overcome urgently.

[0004] As a typical dye absorbing in the near-infrared band, heptamethine cyanine dye has a very high molar extinction coefficient and has been widely used in the field of photodiagnosis and treatment. However, there is relatively little research on it in the field of photopolymerization. The main reason is that the existing heptamethine cyanine dye is difficult to achieve efficient intersystem crossing after being excited by light. This limitation leads to a weakening of the ability of the co-initiator and the initiator to react and generate free radicals to initiate polymerization, thereby affecting the efficiency of the entire photoinitiator system.

[0005] At present, improving the intersystem crossing efficiency of heptamethine cyanine dyes mainly depends on the "heavy atom effect". However, heavy atoms will significantly reduce the solubility of the dyes, affect their dispersion and uniformity in the photopolymerization system, and then affect the performance of the final material, which is not conducive to its application in photopolymerization. Therefore, it is very urgent to rationally design the heptamethine cyanine dye matrix and develop an alternative method without heavy atoms to improve the intersystem crossing to improve the NIR photoinitiation efficiency. Summary of the invention

[0006] In view of the problem that the existing heptamethine cyanine dyes in the prior art cannot produce efficient intersystem crossing and heavy atom effect, the first object of the present invention is to provide a class of para-substituted heptamethine cyanine dyes, which absorb in the near-infrared region, promote efficient intersystem crossing ability through photoinduced electron twisting, and have good photoinitiation effect. The present invention provides the following technical solutions: A class of para-substituted heptamethine cyanine dyes, including the following general formula I:

[0007]

[0008] In the general formula I:

[0009] R1 and R2 are each independently selected from any one of hydrogen, an alkyl group having 1 to 18 carbon atoms, a carboxyalkyl group having 1 to 18 carbon atoms, an aryl group, an arylcarboxylic acid group, an alkyl sulfonate group having 1 to 18 carbon atoms, an aryl sulfonate group, an alkyl sulfonate salt or an aryl sulfonate salt;

[0010] It is further preferred that: R1 and R2 are independently selected from any one of hydrogen, an alkyl group having 1 to 12 carbon atoms, an aryl group, and an alkyl sulfonate group having 1 to 10 carbon atoms;

[0011] More preferably: R1 and R2 are independently selected from any one of hydrogen, a linear alkyl group of 1 to 3 carbon atoms, and a phenyl group;

[0012] R3 and R4 are substituents at undetermined positions of the benzene ring, each independently selected from any one of hydrogen, halogen, methoxy, amino, nitro, hydroxyl, carboxyl, phenyl, naphthyl, an alkylsulfonic acid group having 1 to 18 carbon atoms, an ester group having 1 to 18 carbon atoms, or an amide group having 1 to 18 carbon atoms;

[0013] Preferably: R3 and R4 are substituents at undetermined positions of the benzene ring, each independently selected from any one of hydrogen, halogen, methoxyphenyl, naphthyl, an alkyl sulfonic acid group having 1-12 carbon atoms, an ester group having 1-12 carbon atoms, or an amide group having 1-12 carbon atoms;

[0014] More preferably, R3 and R4 are hydrogen or phenyl;

[0015] R5 is selected from any one of hydrogen, halogen, methyl, trifluoromethyl, keto, aldehyde, phenyl, formate with 1-18 carbon atoms, primary amide, secondary amide with 1-18 carbon atoms, and tertiary amide with 1-18 carbon atoms.

[0016] Preferably, R5 is selected from any one of hydrogen, halogen, methyl, trifluoromethyl, ketone, aldehyde, phenyl, formate group having 1 to 12 carbon atoms, and primary amide group.

[0017] Most preferably, R5 is selected from any one of formaldehyde, ethyl formate, decyl formate, and N,N-dimethylbenzamide.

[0018] X is selected from any one of oxygen, sulfur and selenium; preferably: X is sulfur;

[0019] Y is selected from inorganic anions or organic anions; Y is preferably selected from halogen ions, ClO4 - 、BF4 - 、SbF6 - More preferably, Y is 1 - .

[0020] For the technical solution described above, it is further preferred that the absorption wavelength of the para-substituted heptamethine cyanine dye is above 600nm; preferably, the absorption wavelength of the para-substituted heptamethine cyanine dye is between 600 and 1000nm, and the most preferred range is 600 to 700nm.

[0021] For the technical solution described above, it is further preferred that the molar extinction coefficient of the para-substituted heptamethine quinone cyanine dye is in the range of 1 to 10×10 -4 M -1 cm -1 The preferred range is 2 to 5×10 -4 M -1 cm -1 The most preferred range is 3 to 4×10 -4 M -1 cm -1 , ensuring efficient light absorption capability.

[0022] For the technical solution described above, it is further preferred that the singlet oxygen quantum yield of the para-substituted heptamethine quinone cyanine dye is between 10 and 50%, preferably in the range of 20 to 40%, and most preferably in the range of 30 to 40%, which is significantly higher than that of traditional dyes and is suitable for photodynamic therapy and photocuring applications.

[0023] For the technical solution described above, it is further preferred that the electron transfer free energy of the para-substituted heptamethine quinone cyanine dye is less than 0, indicating that it is easy to undergo electron transfer reaction with the co-initiator.

[0024] For the technical solution described above, it is further preferred that the double bond conversion rate of the para-substituted heptamethine quinone cyanine dye exceeds 20%, preferably in the range of greater than 50%, showing efficient photopolymerization performance.

[0025] The second object of the present invention is to provide a method for synthesizing a class of para-substituted heptamethine quinone cyanine dyes, wherein the preparation method has the advantages of simple synthesis method, cheap raw materials, high yield and high universality.

[0026] The method for synthesizing a para-substituted heptamethine quinone cyanine dye according to any one of claims 1 to 2, characterized in that it comprises:

[0027] (1) mixing a benzothiazole modified with R3 and / or R4 substituents and a halogenated N-alkylating agent with R1 and / or R2 substituents in a molar ratio of 1:(1-10), then adding a first organic solvent, and reacting at 80-130° C. to obtain a quaternary ammonium salt;

[0028] (2) Under a nitrogen atmosphere, add R5-substituted phenol and urotropine to trifluoroacetic acid and mix well, then fully react at 80-120° C., cool, add 1-10 M hydrochloric acid, and continue to react until a light yellow precipitate is obtained; filter to obtain an intermediate product;

[0029] (3) The quaternary ammonium salt and the condensing agent are uniformly mixed, and then a second organic solvent and an alkaline substance are added, and the mixture is fully reacted at 50-150° C., and the solvent is removed to obtain the target product.

[0030] For the technical solution described above, preferably, in step (1), the molar ratio of the benzothiazole modified with R3 and / or R4 substituents to the halogenated N-alkylating agent with R1 and / or R2 substituents is 1:(1.5-5), and most preferably 1:(2-3).

[0031] For the technical solution described above, preferably, in step (1), the first organic solvent is selected from at least one of ethanol, acetonitrile, toluene, DMF, and o-dichlorobenzene, preferably acetonitrile.

[0032] For the technical solution described above, preferably, the reaction temperature in step (1) is preferably 110-120°C.

[0033] For the technical solution described above, preferably, the molar ratio of the phenol substituted by R5 to urotropine in step (2) is (3-10):1, preferably 3-4:1.

[0034] For the technical solution described above, preferably, the reaction temperature of the R5-substituted phenol and urotropine in step (2) is preferably 100-120°C.

[0035] For the technical solution described above, preferably, in step (2), the concentration of hydrochloric acid in the post-treatment reaction of the R5-substituted phenol and urotropine is preferably 3.5-4.5M.

[0036] For the technical solution described above, preferably, the molar ratio of the quaternary ammonium salt to the condensing agent in step (3) is (1-8):1, preferably 1.5-2.5:1.

[0037] For the technical solution described above, preferably, the quaternary ammonium salt in step (3) is selected from 2-methylbenzothiazole quaternary ammonium salt, 2-ethylbenzothiazole quaternary ammonium salt, and 2-propylbenzothiazole quaternary ammonium salt, preferably 2-methylbenzothiazole quaternary ammonium salt.

[0038] For the technical solution described above, preferably, the condensation agent in step (3) is p-hydroxybenzaldehyde, ethylparaben, decyl p-hydroxybenzoate, or 4-hydroxy-N,N-dimethylbenzamide.

[0039] For the technical solution described above, preferably, in step (3), the second organic solvent is selected from at least one of methanol, ethanol, acetic anhydride, n-butanol, isopropanol and acetic acid, preferably methanol.

[0040] For the technical solution described above, preferably, the reaction temperature of the quaternary ammonium salt and the condensation agent in step (3) is preferably 65-75°C.

[0041] For the technical solution described above, preferably, the alkaline substance in step (3) is selected from at least one of sodium acetate, pyridine, potassium carbonate and triethylamine, preferably sodium acetate.

[0042] The third object of the present invention is to provide a class of applications of para-substituted heptamethine quinone cyanine dyes, including photopolymerization, preparation of photodynamic therapy preparations, and applications in the field of biological imaging.

[0043] Specifically, the dye can be used as a triplet photocatalyst to initiate chemical reactions and can be used for photoinitiation in the field of photopolymerization; as a triplet photosensitizer, it can be used in photodynamic therapy to generate reactive oxygen; and as a fluorescent probe for biological imaging.

[0044] For the technical solution described above, it is further preferred that the applications include applications in the fields of near-infrared photoinitiators, photocurable materials, photocatalytic materials, biomedical imaging for non-disease diagnosis and treatment, photodynamic therapy, etc.

[0045] For the technical solution described above, it is further preferred that the para-substituted heptamethine quinone cyanine dye is used as a design and synthesis of NIR photoinitiators, preparation of photocurable resins, deep tissue imaging for non-disease diagnosis and treatment, photocatalytic degradation of pollutants, photopolymerization in photodynamic materials and additive manufacturing (3D printing), and photoresist in the manufacture of microelectronic devices.

[0046] Compared with the prior art, the present invention has the following beneficial effects:

[0047] The present invention successfully improves the absorption characteristics of the heptamethine quinone cyanine dye in the near-infrared region and enhances its singlet oxygen generation ability by introducing a quinone structure and a specific substituent. This not only maintains the original high molar extinction coefficient of the heptamethine cyanine dye, but also solves the problem of low intersystem crossing efficiency of the existing heptamethine cyanine dye after photoexcitation, thereby significantly improving the photoinitiation efficiency.

[0048] The heptamethine quinone cyanine dye molecules of the present invention avoid using heavy atoms to promote intersystem crossing, which not only improves the solubility of the dye, but also reduces potential toxicity and environmental impact, making this type of dye more suitable for use as an environmentally friendly photoinitiator.

[0049] The heptamethine quinone cyanine dye of the present invention exhibits unique absorption and emission spectral characteristics, such as blue shift or red shift phenomenon and large Stokes shift, which is conducive to improving its application potential in deep tissues, especially in the fields of biomedical imaging and treatment.

[0050] In addition to being efficient NIR photoinitiators, the heptamethine quinone cyanine dyes of the present invention also show good electron transfer ability, which makes them have broad application prospects in various photosensitized reactions, including photocatalysis, photodynamic therapy, etc.

[0051] Through reasonable molecular design and simple synthesis process, the present invention provides an economical and effective way to prepare high-performance NIR photoinitiators, reduces production costs, and promotes large-scale production and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 : UV-visible absorption spectra of compounds QMCy7-AcOEt, QMCy7-AcODe, QMCy7-CHO and QMCy7-NC2H6.

[0053] Figure 2 : Fluorescence emission spectra of the compounds.

[0054] Figure 3 : Relative singlet oxygen quantum yield (ΦΔ) test results of compounds 1-3 and comparative examples 1-2.

[0055] Figure 4 :Summary of cyclic voltammetry curves and photolysis rates of QMCy7-R series molecules.

[0056] Figure 5 : EPR spectra detected in free radical capture experiments.

[0057] Figure 6 : Double bond conversion rate and maximum polymerization rate of different initiator combinations in photopolymerization experiments. DETAILED DESCRIPTION

[0058] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0059] Unless otherwise specified, the terms used herein have the following meanings.

[0060] The term "halogen" as used herein includes fluorine, chlorine, bromine and iodine.

[0061] The term "alkyl" as used herein includes, but is not limited to, straight chain alkyl and branched chain alkyl.

[0062] Y is used herein to represent a negative ion, which can be any suitable negative ion, including inorganic negative ions and organic negative ions, and can be exemplified by but not limited to halogen ions, ClO4-, PF4-, BF4 - 、SbF6-.

[0063] The instruments and equipment used in the examples are:

[0064] In the column chromatography process of the present invention, column chromatography silica gel with 200-300 mesh and 100-200 mesh purchased from Qingdao Meigao Group Co., Ltd. and analytical pure quartz sand with 20-40 mesh purchased from Tianda Chemical Reagent Factory are used.

[0065] The absorption spectrum of the initiator was measured using a Cary60 UV-visible spectrophotometer produced by Agilent.

[0066] The triplet quantum yield of the initiator was characterized by the DPBF decay curve method.

[0067] The signal of free radical generated by the initiator was measured by a Bruker Electron Paramagnetic Resonance (A200-9.5 / 12) instrument.

[0068] The polymerization kinetics curve of the photoinitiator was measured by real-time Fourier transform infrared spectroscopy (Nicolet 5700) provided by Beijing Normal University.

[0069] Example 1

[0070] The synthesis method of the para-substituted heptamethine quinone cyanine dye is as follows:

[0071] Synthesis: R1 is methyl, R3 is hydrogen, X is S, and Y is I - The first quaternary ammonium salt QAS-1:

[0072]

[0073] At room temperature, 2-methylbenzothiazole (1.5 g, 10.0 mmol) and iodomethane (2.8 g, 20.0 mmol) were mixed evenly in a 30 mL quartz sealed tube, and then the above reactants were heated to 120°C for 24 hours under stirring. After the reaction was completed, the mixture was cooled to room temperature, and the precipitated solid was washed with ether and dried. Intermediate 1 was a white powdery solid (2.53 g, Y=87%).

[0074] Synthesis of R5 as a condensation agent for ethyl formate:

[0075]

[0076] Under nitrogen protection, ethyl paraben (1.0 g, 6.0 mmol) and urotropine (2.8 g, 20.0 mmol) were dissolved in 10 ml of trifluoroacetic acid and heated to 110° C. for 48 h. The temperature of the reaction system was then lowered to 70° C. and 50 ml of hydrochloric acid (4 M) was added. After the reaction was continued for 3 h, the reaction temperature was lowered to room temperature. A light yellow precipitate was generated, and the precipitate was filtered to obtain a light yellow solid (0.8 g Y=60%).

[0077] Synthesis of target product:

[0078]

[0079] Under nitrogen protection, compound QAS-1 (145 mg, 0.5 mmol) and condensing agent (45 mg, 0.2 mmol) were dissolved in methanol, and sodium acetate (50 mg, 0.61 mmol) was added after they were completely dissolved, and the reaction system was heated to 70°C and refluxed and monitored by silica gel plate. After completion, the solvent was evaporated and the crude product was purified by silica gel column to obtain a metallic luster solid compound (120 mg, Y = 90%).

[0080] 1 H NMR (400MHz, DMSO-d6) δ8.56 (d, J=15.0Hz, 2H), 8.38–8.02 (m, 8H), 7.74 (dt, J =39.5, 7.7Hz, 4H), 4.30 (q, J = 7.1Hz, 2H), 4.20 (s, 6H), 1.35 (t, J = 7.1Hz, 3H).

[0081] ESI-MS (C 29 H 25 N2O3S2)m / z: [M–I] +Calculate 513.1301 and find 513.1304.

[0082] Example 2

[0083] The synthesis method of the para-substituted heptamethine quinone cyanine dye is as follows:

[0084] The first quaternary ammonium salt QAS-1 is the same as in Example 1:

[0085] Synthesis of R5 as a condensation agent for decyl p-hydroxybenzoate:

[0086]

[0087] Under nitrogen protection, decyl p-hydroxybenzoate (1.67 g, 6.0 mmol) and urotropine (2.8 g, 20.0 mmol) were dissolved in 10 ml of trifluoroacetic acid and heated to 110° C. for 48 h. The temperature of the reaction system was then lowered to 70° C. and 50 ml of hydrochloric acid (4 M) was added. After the reaction was continued for 3 h, the reaction temperature was lowered to room temperature. A light yellow precipitate was generated, and the precipitate was filtered to obtain a light yellow solid (0.75 g, Y=38%).

[0088] Synthesis of target product:

[0089]

[0090] Under nitrogen protection, compound QAS-1 (145 mg, 0.5 mmol) and condensing agent (66 mg, 0.2 mmol) were dissolved in methanol, and sodium acetate (50 mg, 0.61 mmol) was added after they were completely dissolved, and the reaction system was heated to 70°C and refluxed and monitored by silica gel plate. After completion, the solvent was evaporated and the crude product was purified by silica gel column to obtain a metallic luster solid compound (130 mg, Y=86%).

[0091] 1 H NMR (400MHz, DMSO-d6) δ8.59 (d, J=15.0Hz, 2H), 8.31 (d, J=8.0Hz, 2H), 8.23 ​​(s, 2H), 8.20–8.11 (m, 4H), 7.79 (t, J=7.8Hz, 2 H), 7.69 (t, J=7.7Hz, 2H), 4.24 (d, J=6.5Hz, 2H), 4.20 (s, 6H), 1.73 (p, J=7.1Hz, 2H), 1.26 (m, 14H), 0.84 (t, J=6.6Hz, 3H).

[0092] ESI-MS (C 37 H 41 N2O3S2)m / z: [M–I] +Calculate 625.2553, find 625.2554.

[0093] Example 3

[0094] The synthesis method of the para-substituted heptamethine quinone cyanine dye is as follows:

[0095] The first quaternary ammonium salt QAS-1 is the same as in Example 1:

[0096] Synthesis of R5 as a condensation agent for 4-hydroxy-N, N-dimethylbenzamide:

[0097]

[0098] Under nitrogen protection, 4-hydroxy-N, N-dimethylbenzamide (1.0 g, 6.0 mmol) and urotropine (2.8 g, 20.0 mmol) were dissolved in 10 ml of trifluoroacetic acid and heated to 110°C for 48 h. The temperature of the reaction system was then lowered to 70°C and 50 ml of hydrochloric acid (4M) was added. After the reaction was continued for 3 h, the reaction temperature was lowered to room temperature. A light yellow precipitate was generated, and the precipitate was filtered to obtain a light yellow solid (0.60 g, Y=45%).

[0099] Synthesis of target product:

[0100]

[0101] Under nitrogen protection, compound QAS-1 (145 mg, 0.5 mmol) and condensing agent (45 mg, 0.2 mmol) were dissolved in methanol, and sodium acetate (50 mg, 0.61 mmol) was added after they were completely dissolved, and the reaction system was heated to 70°C and refluxed and monitored by silica gel plate. After completion, the solvent was evaporated and the crude product was purified by silica gel column to obtain a metallic luster solid compound (98 mg, Y = 77%).

[0102] 1 H NMR (400MHz, DMSO-d6) δ8.42 (d, J=15.2Hz, 2H), 8.29 (d, J=8.1Hz, 2H), 8.19 (s, 1H), 8.16 (s, 1H), 8.11 (d, J=8.5Hz, 2H), 7.89 (s, 2H), 7.77 (t, J=7.9Hz, 2H), 7.67 (t, J=7.7Hz, 2H), 4.18 (s, 6H), 3.05 (s, 6H).

[0103] ESI-MS (C 29 H 26 N3O2S2))m / z: [M–I] +Calculate 512.1461, find 512.1463.

[0104] Comparative Example 1

[0105] The synthesis method of the para-substituted heptamethine quinone cyanine dye is as follows:

[0106] The first quaternary ammonium salt QAS-1 is the same as in Example 1:

[0107] Synthesis of target product:

[0108]

[0109] Under nitrogen protection, compound QAS-1 (145 mg, 0.5 mmol) and 2-hydroxy-1,3,5-benzenetricarboxaldehyde (37 mg, 0.2 mmol) were dissolved in methanol, and sodium acetate (50 mg, 0.61 mmol) was added after they were completely dissolved, and the reaction system was heated to 70°C and refluxed and monitored by silica gel plate. After the reaction, the solvent was evaporated and the crude product was purified by silica gel column to obtain a metallic luster solid compound (80 mg, Y = 67%).

[0110] 1 H NMR (400MHz, DMSO-d6) δ9.63 (s, 1H), 8.46 (d, J=15.0Hz, 2H), 8.32-8.21 (m, 8H), 7.79 (t, J=7.6Hz, 2H), 7.69 (t, J=7.6Hz, 2H), 4.21 (s, 6H).

[0111] ESI-MS (C 27 H 21 N2O2S2)m / z: [M–I] + Calculate 469.1039 and find 469.1043.

[0112] Comparative Example 2

[0113] Comparative Example TCy7 is a commercial dye with the following structure. Its maximum absorption / emission peaks are at 770 nm and 793 nm, respectively.

[0114] This product can be purchased from Bidex Pharmaceuticals Ltd. with a purity of >98%.

[0115]

[0116] Performance Testing

[0117] The compounds QMCy7-AcOEt, QMCy7-AcODe and QMCy7-NC2H6 prepared in Example 1-3 and the compounds QMCy7-CHO and TCy7 prepared in Comparative Example 1-2 were dried, accurately weighed and dissolved in dimethyl sulfoxide to prepare a 1×10 -2 mol / L dye stock solution was placed in a brown sample bottle and stored in a 4°C refrigerator for future use as the dye stock solution.

[0118] 1. Determination of UV-visible absorption spectra and fluorescence spectra of compounds 1-3 and comparative example 1.

[0119] Test method: When testing UV-visible absorption and fluorescence spectra, use a micropipette to measure 3 μL of dye stock solution and dissolve it in a quartz cuvette containing 3 mL of the solvent to be tested, mix well, and obtain a dye concentration of 10 μM for the absorption and fluorescence emission spectra. All tests were completed at 25°C.

[0120] like Figure 1 As shown in Table 1, the maximum absorption peaks of QMCy7-AcOEt and QMCy7-AcODe are about 645 nm, while the maximum absorption peaks of QMCy7-CHO and QMCy7-NC2H6 are about 630 nm and 670 nm, respectively. This indicates that the introduction of electron withdrawing groups (EWG) can cause the wavelength to blue-shift, whereas the introduction of electron donating groups (EDG) can cause the wavelength to red-shift.

[0121] like Figure 2 As shown in Table 1, this electronic effect also has a similar effect on its fluorescence emission wavelength. However, compared with the traditional heptamethine cyanine TCy7, the absorption and emission wavelengths of the QMCy7-R series molecules show a significant blue shift, and the molar extinction coefficient is reduced to 3-4×10 -4 M -1 cm -1 This phenomenon is attributed to the electron-donating properties of oxygen atoms in the quinone structure and their participation in the photon excitation process. In addition, the Stokes shift of the QMCy7-R series molecules is significantly increased (50-60nm) compared to the TCy7 molecule (23nm), indicating that the introduction of the quinone structure increases the non-radiative transition of the excited state. Therefore, the absorption wavelength, molar extinction coefficient and other photophysical properties of the initiator QMCy7-R are comprehensively evaluated, and it is preliminarily determined that it is suitable for deep in situ photoinitiation.

[0122] 2. Test of singlet oxygen generation ability of compound 1-3, comparative example 1-2 and commercial photosensitizer MB in dichloromethane

[0123] Test method: Add 3 mL of dichloromethane solution to a cuvette, add a certain amount of DPBF so that the absorbance of DPBF at 415 nm is about 1.00, then add the dye mother solution of compound 1-3 and comparative example 1 respectively, and adjust the absorbance of the dye at 660 nm to between 0.4-0.6. Illuminate the cuvette under a 660nm LED lamp, and test the ultraviolet absorption of the solution every 1 minute. Then test the DPBF degradation spectrum of MB in the same way, and use the singlet oxygen quantum yield of MB in dichloromethane as a reference to calculate the relative singlet oxygen quantum yield (Φ Δ ). The test results are as follows Figure 3 The calculation results are shown in Table 1.

[0124] like Figure 3 As shown in Table 1, compared with TCy7 dye (Φ Δ =2.6%), the singlet oxygen yield (approximately triplet quantum yield) of QMCy7-R series molecules is as high as 30% or more, among which QMCy7-AcOEt reaches 40.5%, which is about 15.6 times that of TCy7. Therefore, the introduction of carbonyl in the middle of QMCy7-R series molecules is the key factor to improve the ISC ability of molecules, which is attributed to the fact that the oxygen atom in the quinone carbonyl structure can, in some cases, allow the lonely electron on it to participate in the energy transfer of the excited state ( 1 ππ*- 3 nπ* or 1 nπ*-- 3 nππ*), thereby promoting the intersystem crossing process forbidden by spin transition and generating triplet excitons.

[0125] 3. Test the photoinduced electron transfer of compounds 1-3, comparative example 1 and commercial adjuvant IOD, that is, test the redox potential of compounds 1-3 and comparative example 1

[0126] Test method: The concentration of compounds 1-3 and comparative example 1 is 1×10 -3 mol / L, cyclic voltammetry of the compound in N2-saturated DCM with tetrabutylammonium hexafluorophosphate as supporting electrolyte (c=0.1M) and Ag / AgCl as reference electrode. 3 M) as internal reference, scanning rate: 100 mV s -1 , 298K.

[0127] Substitute the obtained data into the formula ΔG=E ox –E red –E e +C calculates the result and analyzes it. ox is the oxidation potential of the initiator, Ered is the reduction potential of Iod, Ee is the energy of the excited state when the initiator is excited (determined by the wavelength of maximum absorption), and the electrostatic interaction (C) is usually negligible in polar solvents.

[0128] Depend on Figure 4 It can be seen that the ΔG of QMCy7-AcOEt is −1.076 eV (electron transfer free energy, as shown in Table 1), which is significantly smaller than that of other initiators (QMCY7-AcODe is −0.837 eV, QMCY7-NC2H6 is −0.878 eV, and QMCY7-CHO is −0.837 eV). Therefore, the electron transfer reaction between QMCy7-AcOEt and IOD is relatively easy to occur.

[0129] Table 1

[0130] Compd. <![CDATA[λ abs (nm) a ]]> <![CDATA[λ em (nm) b ]]> <![CDATA[Δλ(nm) c ]]> <![CDATA[Φ Δ (%) e ]]> ΔG QMCy7-CHO 630 685 55 30.4 -0.837 QMCy7-AcOEt 645 690 45 40.5 -1.075 QMCy7-AcODe 645 690 45 34.4 -0.863 QMCy7-NC2H6 670 730 60 27.2 -0.878 Tx7 770 793 23 0.026 -

[0131] 4. Electron transfer photodegradation experiment

[0132] Test method: Prepare an anhydrous dichloromethane solution of the initiator / IOD system (initiator concentration is 10 μM, IOD concentration is 10 μM). Use a 660 nm laser irradiation intensity of 25 mW / cm -2 The irradiation process was carried out under N2 protection.

[0133] Figure 4 The photolysis rates of the QMCy7-R / IOD system are summarized in the order QMCy7-AcOEt / IOD>

[0134] QMCy7-AcODe / IOD>QMCY7-NC2H6 / IOD>QMCy7-CHO / IOD. Obviously, the photolysis rate is positively correlated with both triplet yield and ΔG. The electron transfer photodegradation experiment is a clear evidence of the electron transfer reaction between QMCy7-R and IOD.

[0135] 5. Free Radical Capture Experiment

[0136] The photoinitiator QMCy7-AcOEt / IOD was prepared at a concentration of 1×10 -3 mol / L -1 tert-butylbenzene solution and 51×10 -3 mol / L -1 Phenyl-N-tert-butylnitrone (PBN) was used as a free radical scavenger. In a dark room, nitrogen was passed through for 15 minutes to remove oxygen. The solution was sucked into a capillary and irradiated with an LED light source with a wavelength of 660 nm. The EPR spectrum was measured under a German Bruker spectrometer.

[0137] like Figure 5 As shown in the figure, no free radical signal was detected in the blank tert-butylbenzene solution after 1 min of irradiation. On the contrary, a strong free radical signal was detected after the addition of QMCy7-AcOEt / IOD. The coupling constants αN and αH were 14.07 and 2.54 G, respectively, which were attributed to the benzene free radicals for polymerization.

[0138] 6. Photopolymerization Experiment

[0139] The photocurable formulation was prepared by free radical polymerization (FRP) by mixing the corresponding monomers and photoinitiator (QMCy7-AcOEt / IOD: 1wt% / 2wt%). The resin mixture was homogenized using ultrasonic vibration and mechanical stirring until uniform. The resin was spread on a thin KBr sheet (thickness = 2mm) and covered with another KBr sheet for photopolymerization. The reduction in TPGDA double bond content was monitored using a Nicolet 5700 FT-IR spectrometer. The conversion of different groups was calculated using the formula.

[0140] Conversion rate (%) = [1-At / A0] × 100%. Where At corresponds to the double bond at time t (about 810 cm -1 ) is the area of ​​the characteristic absorption peak of the group, and A0 represents the initial area of ​​the peak.

[0141] like Figure 6 As shown in the figure, the double bond conversion rates initiated by them are ranked as follows: QMCy7-AcOEt / IOD (70%) > QMCy7-AcODe / IOD (67%) > QMCy7-CHO / IOD (39%) ≈ QMCY7-NC2H6 / IOD (38%) 》 TCy7 / IOD (5%). The maximum polymerization rate values ​​are QMCy7-AcOEt / IOD (0.6%·s -1 )>QMCy7-AcODe / IOD(0.38%·s -1 )>QMCy7-CHO / IOD(0.1%·s -1 )>QMCY7-NC2H6 / IOD(0.05%·s -1 ). At the same time, after light irradiation, QMCy7-AcOEt / IOD showed no obvious inhibition period. Therefore, QMCy7-AcOEt / IOD has good time response and double bond conversion rate in all cases. This performance of photoinitiated polymerization is consistent with the photophysical properties discussed above. The results show that QMCy7-AcOEt / IOD can play a potential role as a two-component type II initiator in free radical polymerization.

[0142] In summary, the meso-substituted heptamethine quinone cyanine dyes have better photopolymerization ability than the unsubstituted dyes.

[0143] Compared with the prior art, the dye provided by the present invention has successfully developed a new dye structure and studied its photophysical properties; the absorption wavelength is located in the near-infrared light region, deep and strong; has high intersystem crossing efficiency; can catalyze the co-initiator to generate free radicals for photopolymerization; and can be better used in practical applications.

[0144] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various changes or modifications within the scope of the claims, which does not affect the essence of the present invention. In the absence of conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.

Claims

1. A para-substituted heptamethine quinone cyanine dye, characterized in that: Its structural formula is shown in general formula I: In the general formula I: R1 and R2 are each independently selected from any one of hydrogen, an alkyl group having 1 to 18 carbon atoms, a carboxyalkyl group having 1 to 18 carbon atoms, an aryl group, an arylcarboxylic acid group, an alkyl sulfonate group having 1 to 18 carbon atoms, an aryl sulfonate group, an alkyl sulfonate salt or an aryl sulfonate salt; R3 and R4 are substituents at undetermined positions of the benzene ring, each independently selected from any one of hydrogen, halogen, methoxy, amino, nitro, hydroxyl, carboxyl, phenyl, naphthyl, an alkylsulfonic acid group having 1 to 18 carbon atoms, an ester group having 1 to 18 carbon atoms, or an amide group having 1 to 18 carbon atoms; R5 is selected from any one of hydrogen, halogen, methyl, trifluoromethyl, keto, aldehyde, phenyl, formate with 1 to 18 carbon atoms, primary amide, secondary amide with 1 to 18 carbon atoms, and tertiary amide with 1 to 18 carbon atoms; X is selected from any one of oxygen, sulfur and selenium; Y is selected from inorganic anions or organic anions.

2. The dye according to claim 1, characterized in that: The absorption wavelength of the para-substituted heptamethine quinone cyanine dye is above 600 nm; the molar extinction coefficient is between 1 and 10×10 -4 M -1 cm -1 The singlet oxygen quantum yield is between 10% and 50%. The electron transfer free energy is less than 0. The double bond conversion rate exceeds 20%.

3. A method for synthesizing a para-substituted heptamethine quinone cyanine dye as claimed in claim 1, comprising the following steps: (1) mixing a benzothiazole modified with R3 and / or R4 substituents and a halogenated N-alkylating agent with R1 and / or R2 substituents in a molar ratio of 1:(1-10), then adding a first organic solvent, and reacting at 80-130° C. to obtain a quaternary ammonium salt; (2) Under a nitrogen atmosphere, add R5-substituted phenol and urotropine to trifluoroacetic acid and mix well, then fully react at 80-120° C., cool, add 1-10 M hydrochloric acid, and continue to react until a light yellow precipitate is obtained; filter to obtain an intermediate product; (3) The quaternary ammonium salt and the condensing agent are uniformly mixed, and then a second organic solvent and an alkaline substance are added, and the mixture is fully reacted at 50-150° C., and the solvent is removed to obtain the target product.

4. The method according to claim 3, characterized in that: In step (1), the molar ratio of the benzothiazole modified with R3 and / or R4 substituents to the halogenated N-alkylating agent with R1 and / or R2 substituents is 1:(1.5-5).

5. The method according to claim 3, characterized in that: In step (1), the first organic solvent is selected from at least one of ethanol, acetonitrile, toluene, DMF and o-dichlorobenzene.

6. The method according to claim 3, characterized in that: The molar ratio of the R5-substituted phenol to hexamethylenetetramine in step (2) is (3-10):

1.

7. The method according to claim 3, characterized in that: The molar ratio of the quaternary ammonium salt to the condensing agent in step (3) is (1-8):

1.

8. The method according to claim 3, characterized in that: The quaternary ammonium salt in step (3) is selected from one of 2-methylbenzothiazole quaternary ammonium salt, 2-ethylbenzothiazole quaternary ammonium salt, and 2-propylbenzothiazole quaternary ammonium salt; the condensing agent is p-hydroxybenzaldehyde, ethylparaben, decyl p-hydroxybenzoate, and 4-hydroxy-N,N-dimethylbenzamide; and the alkaline substance is selected from at least one of sodium acetate, pyridine, potassium carbonate, and triethylamine.

9. The method according to claim 3, characterized in that: In step (3), the second organic solvent is selected from at least one of methanol, ethanol, acetic anhydride, n-butanol, isopropanol and acetic acid.

10. The application of the dye according to claim 1, including photopolymerization, preparation of photodynamic therapy preparations, and application in the field of biological imaging.

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