Para-substituted heptamethine cyanine dyes and methods of synthesis and use thereof

Abstract

The application discloses a kind of para-substituted heptamethine cyanine dye and its synthesis method and application, its structure general formula is as shown in I, i.e. by introducing specific quinone structure and substituent, near-infrared light absorption and triplet excited state generation ability are optimized.Dye is absorbed in the wavelength range of 600-700 nanometer high efficiency light, and significantly improves intersystem crossing efficiency, enhances photo-initiation effect.The dye avoids using heavy atom, improves solubility and environmental protection.Synthesis method is simple, low cost, mild condition, suitable for mass production.Key steps include quaternary ammonium salt formation, condensing agent preparation and final product synthesis, each step parameter is optimized to ensure high yield.This kind of dye is suitable for photodynamic therapy, photo-initiation of photo-polymerization material, biological imaging and the like, and shows wide application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of near-infrared light initiator synthesis, in particular to a kind of para-substituted heptamethine cyanine dye and its synthesis method and application. BACKGROUND

[0002] Photopolymerization technology is considered as an environmentally friendly, precise, safe and efficient method for building macromolecular materials. Therefore, this technology has been widely used in the fields of additive manufacturing and photoresist. Photoinitiator (PI) as a key component of photopolymerization system is crucial to determine the rate and degree of photopolymerization and the performance of the resulting material. According to the emission wavelength of the absorbable irradiation 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, due to the disadvantages of ultraviolet light source, such as high energy consumption, short service life and ozone release, UV type PI is limited. In contrast, NIR type PI shows a trend to replace UV type due to the specific characteristics provided by NIR light source. Therefore, NIR photoinitiators have received great attention in recent years, and the design and development of dye molecules with near-infrared absorption characteristics and high efficiency photoinitiation have become a pressing problem to be solved.

[0004] Heptamethine cyanine dye, as a typical dye absorbing in near-infrared band, has very high molar extinction coefficient and has been widely used in the field of photodiagnosis and treatment. However, its research in the field of photopolymerization is relatively less, the main reason is that the existing heptamethine cyanine dye is difficult to achieve high efficiency intersystem crossing process after being excited by light. This limitation leads to the weakening of the ability of reactive collision between co-initiator and initiator to generate free radicals to start polymerization, thereby affecting the efficiency of the entire photoinitiation system.

[0005] Currently, the improvement of intersystem crossing efficiency of heptamethine cyanine dye mainly depends on the "heavy atom effect". However, heavy atoms can significantly reduce the solubility of the dye, affecting its dispersion and uniformity in the photopolymerization system, and further affecting the performance of the final material, which is not conducive to its application in photopolymerization. Therefore, it is very urgent to reasonably design the heptamethine cyanine dye matrix and develop an alternative method to improve the intersystem crossing without heavy atoms to improve the efficiency of NIR photoinitiation. SUMMARY

[0006] In view of the problem that the existing heptamethine cyanine dye cannot occur efficient intersystem crossing and heavy atom effect in the prior art, the first object of the present application is to provide a kind of para-substituted heptamethine cyanine dye, the para-substituted heptamethine cyanine dye is absorbed in the near infrared region, efficient intersystem crossing ability is promoted by light-induced electronic torsion, and good light initiation effect is obtained.The present application provides the following technical scheme: a kind of para-substituted heptamethine cyanine dye, comprising the following general formula I:

[0007]

[0008] In general formula I:

[0009] R1 and R2 are each independently selected from any one of hydrogen, alkyl of 1-18 carbons, carboxyalkyl of 1-18 carbons, aryl, aryl carboxylic acid group, alkyl sulfonate of 1-18 carbons, aryl sulfonate, alkyl sulfonate or aryl sulfonate;

[0010] Further preferably, R1 and R2 are each independently selected from any one of hydrogen, alkyl of 1-12 carbons, aryl, alkyl sulfonate of 1-10 carbons;

[0011] More preferably, R1 and R2 are each independently selected from any one of hydrogen, linear alkyl of 1-3 carbons, and phenyl;

[0012] R3 and R4 are substituents at uncertain positions of a benzene ring, and are each independently selected from any one of hydrogen, halogen, methoxy, amino, nitro, hydroxyl, carboxyl, phenyl, naphthyl, alkyl sulfonate of 1-18 carbons, ester group of 1-18 carbons, or amide group of 1-18 carbons;

[0013] Preferably, R3 and R4 are substituents at uncertain positions of a benzene ring, and are each independently selected from any one of hydrogen, halogen, methoxy, naphthyl, alkyl sulfonate of 1-12 carbons, ester group of 1-12 carbons, or amide group of 1-12 carbons;

[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 group of 1-18 carbons, acyl primary amide, acyl secondary amide of 1-18 carbons, and acyl tertiary amide of 1-18 carbons.

[0016] Preferably, R5 is selected from any one of hydrogen, halogen, methyl, trifluoromethyl, keto, aldehyde, phenyl, formate group of 1-12 carbons, and acyl primary amide.

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

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

[0019] Y is selected from any one of inorganic anions or organic anions; Y is preferably selected from any one of halogen ions, ClO4 - , BF4 - , SbF6 - ; more preferably, Y is I - .

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

[0021] For the technical solutions described above, it is further preferred that the molar extinction coefficient of the para-substituted heptamethine cyanine dye is between 1 and 10 x 10 -4 M -1 cm -1 , preferably between 2 and 5 x 10 -4 M -1 cm -1 , and most preferably between 3 and 4 x 10 -4 M -1 cm -1 , ensuring high light absorption capacity.

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

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

[0024] For the technical solutions described above, it is further preferred that the double bond conversion rate of the para-substituted heptamethine cyanine dye is more than 20%, and preferably more than 50%, demonstrating high photo-polymerization performance.

[0025] The second object of the present application is to provide a synthesis method of a para-substituted heptamethine cyanine dye, which has the advantages of simple synthesis method, cheap raw materials, high yield, and high universality.

[0026] The method for synthesizing a type of para-substituted heptamethrin cyanine dye according to any one of claims 1-2 is characterized by comprising:

[0027] (1) Mix benzothiazole modified with R3 and / or R4 substituents with halo-N-alkylating reagent with R1 and / or R2 substituents at a molar ratio of 1:(1-10) until homogeneous, then add the first organic solvent and react fully at 80-130℃ to obtain quaternary ammonium salt.

[0028] (2) Under a nitrogen atmosphere, R5-substituted phenol and hexamethylenetetramine were added to trifluoroacetic acid and mixed evenly. After the mixture was fully reacted at 80-120°C, it was cooled and 1-10M hydrochloric acid was added. The reaction was continued until a pale yellow precipitate was obtained. The intermediate product was obtained by filtration.

[0029] (3) Mix the quaternary ammonium salt and condensing agent evenly, then add the second organic solvent and alkaline substance, react fully at 50-150℃, remove the solvent, and obtain the target product.

[0030] For the technical solution described above, preferably, the molar ratio of the benzothiazole modified with R3 and / or R4 substituents in step (1) to the halo-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, the first organic solvent in step (1) is selected from at least one of ethanol, acetonitrile, toluene, DMF, and o-dichlorobenzene, with acetonitrile being the most preferred.

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

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

[0034] For the technical solution described above, preferably, the reaction temperature of the R5-substituted phenol with hexamethylenetetramine in step (2) is 100-120℃.

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

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

[0037] For the technical solution described above, preferably, 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. Preferably, it is 2-methylbenzothiazole quaternary ammonium salt.

[0038] For the technical solution described above, preferably, the condensing 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, the second organic solvent in step (3) is selected from at least one of methanol, ethanol, acetic anhydride, n-butanol, isopropanol, and acetic acid, with methanol being preferred.

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

[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, with sodium acetate being the most preferred.

[0042] A third objective of this invention is to provide applications of a class of para-substituted heptamethrin cyanine dyes, including photopolymerization, preparation of photodynamic therapy formulations, and applications in the field of bioimaging.

[0043] Specifically, this 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 to generate reactive oxygen species in photodynamic therapy; and as a fluorescent probe for bioimaging.

[0044] For the technical solution described above, more preferably, the application includes applications in the fields of near-infrared photoinitiators, photocurable materials, photocatalytic materials, biomedical imaging in the direction of non-disease diagnosis and treatment, and photodynamic therapy.

[0045] Further preferably, the para-substituted heptamethine cyanine dye is used in the design and synthesis of NIR photoinitiators, the 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 microelectronic device manufacturing.

[0046] Compared with the prior art, the beneficial effects of the present invention are as follows:

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

[0048] The heptamethrin cyanine dye molecules of the present invention avoid the use of heavy atoms to promote intersystem crossing, which not only improves the solubility of the dye, but also reduces potential toxicity and environmental impact, making such dyes more suitable for use as environmentally friendly photoinitiators.

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

[0050] In addition to being highly efficient NIR photoinitiators, the heptamethrin cyanine dyes of this invention also exhibit excellent electron transfer capabilities, which makes them promising for a wide range of applications in various photosensitizing reactions, including photocatalysis and photodynamic therapy.

[0051] Through rational molecular design and simple synthesis process, this invention provides an economical and effective way to prepare high-performance NIR photoinitiators, reducing production costs and promoting large-scale production and application. Attached Figure Description

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

[0053] Figure 2 : The fluorescence emission spectrum of the compound.

[0054] Figure 3 Results of relative singlet oxygen quantum yield (ΦΔ) tests for 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 spectrum detected in free radical capture experiment.

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

[0058] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

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

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

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

[0062] In this article, Y represents negative ions, which can be any suitable negative ion, including inorganic and organic negative ions. Examples include, but are not limited to, halide ions, ClO4-, PF4-, and BF4-. - 、SbF6-.

[0063] The instruments and equipment used in the embodiments are as follows:

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

[0065] The initiator absorption spectrum was measured using an Agilent Cary 60 UV-Vis spectrophotometer.

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

[0067] The signal of free radical generation by the initiator was measured by a Bruker electron paramagnetic resonance (A200-9.5 / 12) instrument.

[0068] The polymerization kinetics curves of the photoinitiator were measured using a real-time Fourier transform infrared spectrometer (Nicolet 5700) provided by Beijing Normal University.

[0069] Example 1

[0070] The synthesis method of para-substituted heptamethrin cyanine dyes is as follows:

[0071] Synthesized with R1 as methyl, R3 as hydrogen, X as S, and Y as I. - First quaternary ammonium salt QAS-1:

[0072]

[0073] 2-Methylbenzothiazole (1.5 g, 10.0 mmol) and methyl iodide (2.8 g, 20.0 mmol) were mixed thoroughly in a 30 mL sealed quartz tube at room temperature. The mixture was then heated to 120 °C with stirring and reacted for 24 hours. After the reaction was complete, the mixture was cooled to room temperature, and the precipitated solid was washed with diethyl ether and dried. Intermediate 1 was a white powdery solid (2.53 g, Y = 87%).

[0074] R5 is a condensing agent for synthesizing ethyl formate.

[0075]

[0076] Ethylparaben (1.0 g, 6.0 mmol) and hexamethylenetetramine (2.8 g, 20.0 mmol) were dissolved in 10 mL of trifluoroacetic acid under nitrogen protection and the mixture was heated to 110 °C for 48 h. The reaction mixture was then cooled to 70 °C and 50 mL of hydrochloric acid (4 M) was added. The reaction was continued for 3 h, and then cooled to room temperature. A pale yellow precipitate formed, which was filtered to obtain a pale yellow solid (0.8 g, Y = 60%).

[0077] Synthesis of the target product:

[0078]

[0079] Compound QAS-1 (145 mg, 0.5 mmol) and a condensing agent (45 mg, 0.2 mmol) were dissolved in methanol under nitrogen protection. After complete dissolution, sodium acetate (50 mg, 0.61 mmol) was added, and the reaction system was heated to 70 °C and refluxed, with the reaction monitored using a silica gel plate. After the reaction was completed, the solvent was evaporated, and the crude product was purified by silica gel column chromatography to obtain a metallic 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 para-substituted heptamethrin cyanine dyes is as follows:

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

[0085] R5 is a condensing agent for the synthesis of decyl p-hydroxybenzoate:

[0086]

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

[0088] Synthesis of the target product:

[0089]

[0090] Compound QAS-1 (145 mg, 0.5 mmol) and a condensing agent (66 mg, 0.2 mmol) were dissolved in methanol under nitrogen protection. After complete dissolution, sodium acetate (50 mg, 0.61 mmol) was added, and the reaction system was heated to 70 °C and refluxed, with the reaction monitored using a silica gel plate. After the reaction was completed, the solvent was evaporated, and the crude product was purified by silica gel column chromatography to obtain a metallic 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 and find 625.2554.

[0093] Example 3

[0094] The synthesis method of para-substituted heptamethrin cyanine dyes is as follows:

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

[0096] R5 is a condensing agent for the synthesis of 4-hydroxy-N,N-dimethylbenzamide.

[0097]

[0098] 4-Hydroxy-N,N-dimethylbenzamide (1.0 g, 6.0 mmol) and hexamethylenetetramine (2.8 g, 20.0 mmol) were dissolved in 10 mL of trifluoroacetic acid under nitrogen protection and the mixture was heated to 110 °C for 48 h. The reaction mixture was then cooled to 70 °C and 50 mL of hydrochloric acid (4 M) was added. The reaction was continued for 3 h, and then cooled to room temperature. A pale yellow precipitate formed, which was filtered to obtain a pale yellow solid (0.60 g, Y = 45%).

[0099] Synthesis of the target product:

[0100]

[0101] Compound QAS-1 (145 mg, 0.5 mmol) and a condensing agent (45 mg, 0.2 mmol) were dissolved in methanol under nitrogen protection. After complete dissolution, sodium acetate (50 mg, 0.61 mmol) was added, and the reaction system was heated to 70 °C and refluxed, with the reaction monitored using a silica gel plate. After the reaction was completed, the solvent was evaporated, and the crude product was purified by silica gel column chromatography to obtain a metallic 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 and find 512.1463.

[0104] Comparative Example 1

[0105] The synthesis method of para-substituted heptamethrin cyanine dyes is as follows:

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

[0107] Synthesis of the target product:

[0108]

[0109] Compound QAS-1 (145 mg, 0.5 mmol) and 2-hydroxy-1,3,5-benzenetrialdehyde (37 mg, 0.2 mmol) were dissolved in methanol under nitrogen protection. After complete dissolution, sodium acetate (50 mg, 0.61 mmol) was added, and the reaction system was heated to 70 °C and refluxed, with the reaction monitored using a silica gel plate. After the reaction was completed, the solvent was evaporated, and the crude product was purified by silica gel column chromatography to obtain a metallic 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, find 469.1043.

[0112] Comparative Example 2

[0113] The comparative example, TCy7, is a commercial dye with the following structure, and its maximum absorption / emission peaks are located at 770 nm and 793 nm, respectively.

[0114] This product is available from Bid Pharmaceutical Co., Ltd., and its purity is >98%.

[0115]

[0116] Performance testing

[0117] The compounds QMCy7-AcOEt, QMCy7-AcODe, and QMCy7-NC2H6 obtained in Examples 1-3, and the compounds QMCy7-CHO and TCy7 obtained in Comparative Examples 1-2, were dried, accurately weighed, and dissolved in dimethyl sulfoxide to obtain a concentration of 1×10⁻⁶. -2 The dye stock solution of mol / L was placed in a brown sample bottle and stored in a refrigerator at 4°C for future use.

[0118] 1. Determination of UV-Vis absorption and fluorescence spectra of compounds 1-3 and Comparative Example 1.

[0119] Test method: When testing the UV-Vis absorption and fluorescence spectra, 3 μL of the dye stock solution was measured using a micropipette and dissolved in a quartz cuvette containing 3 mL of the test solvent. The mixture was thoroughly mixed to obtain a dye concentration of 10 μM, which was used for testing the absorption and fluorescence emission spectra. All tests were performed at 25 °C.

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

[0121] like Figure 2 As shown in Table 1, this electronic effect also has a similar impact on its fluorescence emission wavelength. However, compared to the traditional heptamethrin TCy7, the QMCy7-R series molecules show a significant blue shift in both absorption and emission wavelengths, and their molar extinction coefficients are reduced to 3–4 × 10⁻⁴. -4 M -1 cm -1 This phenomenon is attributed to the electron-donating properties of the oxygen atom in the quinone structure and its participation in the photon excitation process. Furthermore, the Stokes shift of the QMCy7-R series molecules is significantly increased (50-60 nm) compared to the TCy7 molecule (23 nm), indicating that the introduction of the quinone structure increases the nonradiative transition of the excited state. Therefore, based on a comprehensive evaluation of the photophysical properties of the initiator QMCy7-R, such as absorption wavelength and molar extinction coefficient, it is preliminarily determined that it is suitable for deep in-situ photoinitiation.

[0122] 2. Tests on the singlet oxygen generation capacity of compounds 1-3, comparative examples 1-2, and the commercial photosensitizer MB in dichloromethane.

[0123] Test method: Add 3 mL of dichloromethane solution to a cuvette, then add a certain amount of DPBF to make the absorbance of DPBF at 415 nm approximately 1.00. Then add the dye stock solutions of compounds 1-3 and Comparative Example 1 respectively, adjusting the absorbance of the dye at 660 nm to between 0.4 and 0.6. Illuminate the cuvette under a 660 nm LED lamp, and measure the UV absorption of the solution every 1 min. Then, test the DPBF degradation spectrum of MB using the same method. Using the singlet oxygen quantum yield of MB in dichloromethane as a reference, calculate the relative singlet oxygen quantum yield (Φ) of compounds 1-3 and Comparative Examples 1-2. Δ The test results are as follows: Figure 3 As shown in Table 1, the calculation results are as follows.

[0124] like Figure 3 And as shown in Table 1, compared to TCy7 dye (Φ Δ =2.6%), the singlet oxygen yield (approximately triplet quantum yield) of the QMCy7-R series molecules is as high as 30% or more, with QMCy7-AcOEt reaching 40.5%, about 15.6 times that of TCy7. Therefore, the introduction of a carbonyl group at the mid-position in the QMCy7-R series molecules is a key factor in improving the molecular ISC ability. This is attributed to the fact that the oxygen atom in the quinone carbonyl structure can, under certain circumstances, allow its lonely electron to participate in the energy transfer of the excited state ( =2.6%). 1 ππ*- 3 nπ* or 1 nπ*-- 3 This promotes the intersystem crossing process that is forbidden by spin transitions, thereby generating triplet excitons.

[0125] 3. Photoinduced electron transfer was tested on compounds 1-3, Comparative Example 1, and the commercially available auxiliary IOD, i.e., the redox potentials of compounds 1-3 and Comparative Example 1 were tested.

[0126] Test method: The concentration of compounds 1-3 and comparative example 1 is 1×10⁻⁶. -3 Cyclic voltammetry of compounds in a N2-saturated DCM with a concentration of mol / L, using tetrabutylammonium hexafluorophosphate as the supporting electrolyte (c = 0.1 M) and Ag / AgCl as the reference electrode. Ferrocene (Fc) (c = 10⁻⁶ mol / L) was used as the reference electrode. 3 M) is used as an internal reference, scan rate: 100 mV / s -1 ,298K.

[0127] Substitute the obtained data into the formula ΔG=E ox –E red –E e The results are calculated using +C and analyzed. Where E... ox It is the oxidation potential of the initiator, Ered Iod is the reduction potential of Iod, Ee is the energy of the excited state when excited by the initiator (determined by the maximum absorption wavelength), and 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. abs (nm) a ]]> ​ em (nm) b ]]> ​ Δλ (nm) c ]] Φ Δ (%) e ]] AG 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 TCy7 770 793 23 0.026 -

[0131] 4. Electron transfer photodegradation experiment

[0132] Experimental method: An anhydrous dichloromethane solution of the initiator / IOD system was prepared (initiator concentration: 10 μM, IOD concentration: 10 μM). Irradiation was performed using a 660 nm laser at an intensity of 25 mW / cm². -2 The irradiation process is protected under N2.

[0133] Figure 4 The photolysis rates of the QMCy7-R / IOD system were summarized, and the order was QMCy7-AcOEt / IOD >

[0134] QMCy7-AcODe / IOD > QMCY7-NC2H6 / IOD > QMCy7-CHO / IOD. Clearly, the photolysis rate is positively correlated with both the triplet yield and ΔG. Electron-transfer photodegradation experiments provide strong evidence of electron transfer reactions between QMCy7-R and IOD.

[0135] 5. Free radical capture experiment

[0136] The photoinitiator QMCy7-AcOEt / IOD was prepared at a concentration of 1×10⁻⁶. -3 mol / L -1 tert-butylbenzene solution and 51×10 -3 mol / L -1 Phenyl-N-tert-butylnitroketone (PBN) was used as a free radical scavenger. Oxygen was removed by purging with nitrogen for 15 minutes in a dark chamber. The solution was then drawn into a capillary tube and irradiated with an LED light source at a wavelength of 660 nm. The EPR spectrum was measured using a Bruker spectrometer (Germany).

[0137] likeFigure 5 As shown, no free radical signal was detected in PBN after irradiation of the blank tert-butylbenzene solution for 1 min. Conversely, 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 benzene free radicals, thus initiating the polymerization reaction.

[0138] 6. Photopolymerization Experiment

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

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

[0141] like Figure 6 As shown, the double bond conversion rates they induce 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). -1 QMCy7-AcODe / IOD(0.38%·s) -1 QMCy7-CHO / IOD (0.1%·s) -1 QMCY7-NC2H6 / IOD(0.05%·s) -1 Furthermore, after light irradiation, QMCy7-AcOEt / IOD showed no significant inhibition period. Therefore, QMCy7-AcOEt / IOD exhibited good time response and double bond conversion rate in all cases. This property of photoinitiated polymerization is consistent with the photophysical properties discussed above. The results indicate that QMCy7-AcOEt / IOD has potential as a two-component type II initiator in radical polymerization.

[0142] In summary, meso-substituted heptamethrin cyanine dyes exhibit superior photopolymerization capabilities compared to unsubstituted dyes.

[0143] Compared with existing technologies, the dyes provided by this invention have: successfully developed new dye structures and studied their photophysical properties; their absorption wavelengths are all located in the near-infrared region, with strong deep absorption; they have high intersystem crossing efficiency; they can catalyze the generation of free radicals from co-initiators for photopolymerization; and thus can be better used in practical applications.

[0144] Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention. Unless otherwise specified, the embodiments and features described in this application can be arbitrarily combined with each other.

Claims

1. A class of para-substituted heptamethrin cyanine dyes, characterized in that, Its structural formula is shown in general formula I: In general formula I: R1 and R2 are each independently selected from hydrogen-containing alkyl groups having 1 to 12 carbons; R3 and R4 are substituents at uncertain positions on the benzene ring, each independently selected from hydrogen or halogen. R5 is selected from any one of hydrogen, formate group having 1-12 carbons, and amide group; X is selected from any one of oxygen, sulfur, and selenium; Y is selected from halide ions, ClO4-, BF4-. - SbF6 - .

2. The dye according to claim 1, characterized in that: The para-substituted heptamethrin cyanine dye has an absorption wavelength above 600 nm and a molar extinction coefficient of 1 to 10 × 10⁻⁶. -4 M -1 cm -1 Between; singlet oxygen quantum yield between 10% and 50%; electron transfer free energy less than 0; double bond conversion rate exceeding 20%.

3. The method for synthesizing a type of para-substituted heptamethrin cyanine dye as described in claim 1, comprising the following steps: (1) Mix benzothiazole modified with R3 and / or R4 substituents with halo-N-alkylating reagent with R1 and / or R2 substituents at a molar ratio of 1:(1-10) until homogeneous, then add the first organic solvent and react fully at 80-130℃ to obtain quaternary ammonium salt. (2) Under a nitrogen atmosphere, R5-substituted phenol and hexamethylenetetramine were added to trifluoroacetic acid and mixed evenly. After the mixture was fully reacted at 80-120°C, it was cooled and 1-10M hydrochloric acid was added. The reaction was continued until a pale yellow precipitate was obtained. The intermediate product was obtained by filtration. (3) Mix the quaternary ammonium salt and condensing agent evenly, then add the second organic solvent and alkaline substance, react fully at 50-150℃, remove the solvent, and obtain the target product.

4. The method according to claim 3, characterized in that: The molar ratio of the benzothiazole modified with R3 and / or R4 substituents in step (1) to the halo-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 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 and the condensing agent in step (3) is (1-8):

1.

8. The method according to claim 3, characterized in that: In step (3), the quaternary ammonium salt 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 as described in claim 1, for non-disease diagnostic or therapeutic purposes, in the field of preparing photopolymers or for use in photodynamic therapy formulations.

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