Selenium-substituted hemicyanine dye precursor and synthesis method and application thereof

Abstract

The application discloses a selenium-substituted hemicyanine dye precursor and a synthesis method and application thereof, and belongs to the fine chemical field. The structure of the selenium-substituted hemicyanine dye precursor is shown in a general formula I. In the general formula I, R1 is one of H, a phenyl group, a p-phenyl benzyl chloride, a p-phenyl benzyl bromide, SO3R4, COOR4 or C1-C 12 alkyl; R2 is C, S or Se; R3 is one of H, a phenyl group or C1-C 12 alkyl; R4 is H or C1-C 12 alkyl; and Y is Cl, Br or I. The application provides a selenium-substituted hemicyanine dye precursor, which has near-infrared absorption and emission spectral performance and high active oxygen generation capacity, and provides an ideal platform for constructing dye photosensitizers.

Description

Technical Field

[0001] This invention belongs to the field of fine chemicals and relates to a selenium-substituted hemicyanine dye parent material, its synthesis method, and its application. Background Technology

[0002] Photodynamic therapy (PDT) is an effective method for treating diseases by utilizing the photodynamic effect of photosensitizer dyes. It has attracted considerable attention from researchers, especially in the treatment of tumors, due to its advantages such as high selectivity, good therapeutic effect, and low drug resistance. The current clinical photodynamic therapy process for tumors involves the photosensitizer dye first reaching a singlet excited state under light excitation at a specific wavelength (…). 1 PS * ) and then via intersystem crossing (ISC) to the triplet excited state ( 3 PS * Long-lived triplet-excited-state photosensitizers generate highly toxic reactive oxygen species (ROS) through type I and II photodynamic processes to kill tumor cells. Therefore, the performance of photosensitizer dyes largely determines the effectiveness of tumor photodynamic therapy (PDT). However, most reported photosensitizer dyes are "always-on" photosensitizers, which cannot avoid damaging normal tissues during tumor PDT. Activable photosensitizer dyes only regain their photosensitivity after being activated by overexpressed biomarkers within the tumor, fundamentally solving the drawbacks of "always-on" photosensitizer dyes. A common strategy for constructing photosensitizer matrices is to introduce heavy atoms (such as iodine atoms) onto the original fluorophore matrix to enhance spin-orbit coupling and improve intersystem crossing, thereby increasing photosensitivity. However, high dark toxicity and reduced triplet lifetimes affect the clinical translation prospects of dye photosensitizers. Therefore, developing an ideal activatable photosensitizer dye matrix platform is particularly important.

[0003] Oxygen-substituted hemicyanine dyes possess advantages such as near-infrared absorption and emission, tunable spectral properties, good photostability, and large Stokes shifts, making them a class of high-performance fluorescent dyes widely used in bioimaging and biolabeling. However, due to their low ability to generate reactive oxygen species, they are difficult to use in photodynamic therapy for tumors / bacteria. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention provides a selenium-substituted hemicyanine dye parent material, its synthesis method, and its application. This invention significantly enhances photosensitivity while maintaining low dark toxicity through the regulation of excited states.

[0005] In a first aspect, the present invention provides a selenium-substituted hemicyanine dye parent material, the structure of which is shown in general formula I:

[0006]

[0007] In general formula I:

[0008] R1 is H, phenyl, p-phenylbenzyl chloride, p-phenylbenzyl bromide, SO3R4, COOR4, or C1-C. 12 One of the alkyl groups;

[0009] R2 is C, S, or Se;

[0010] R3 is H, phenyl, or C1-C. 12 One of the alkyl groups;

[0011] R4 is H or C1-C 12 One of the alkyl groups

[0012] Y can be Cl, Br, or I.

[0013] Preferably, R2 is Se.

[0014] Preferably, R3 is H or phenyl.

[0015] Preferably, Y is Br or I.

[0016] Secondly, the present invention provides a method for synthesizing a selenium-substituted hemicyanine dye parent material, comprising the following steps:

[0017] (1) Compound 3 was prepared by reacting compound 1 and compound 2 in a molar ratio of 1:3.0 to 5.0;

[0018]

[0019] (2) Compound 5 was prepared by reacting compounds 3 and 4 in a molar ratio of 2.0 to 2.5:1;

[0020]

[0021] (3) Compound 6 and compound 7 reacted in a molar ratio of 1:2.0 to 3.0 to prepare compound 8;

[0022]

[0023] (4) Compounds 5 and 8 react in a molar ratio of 1:1.2 to 1.5 to prepare compounds of general formula I.

[0024]

[0025] Furthermore, in the above technical solution, in step (1), the reaction solvent for compound 1 and compound 2 is acetonitrile, and the reaction conditions are 85-90℃ for 4-5 hours.

[0026] Furthermore, in the above technical solution, in step (2), the reaction solvent for compound 3 and compound 4 is a mixed solution of acetic acid, acetic anhydride and triethylamine, and the reaction conditions are 65-70℃ for 1-3 hours.

[0027] Furthermore, in the above technical solution, the volume ratio of acetic acid, acetic anhydride and triethylamine in the mixed solution is 2-3:1:1.

[0028] Furthermore, in the above technical solution, in step (3), the reaction solvent for compound 6 and compound 7 is dimethyl sulfoxide, with AgNO3 as the catalyst, and the reaction conditions are 120-130℃ for 2-3 hours.

[0029] Furthermore, in the above technical solution, in step (4), before the compound 8 reacts with the compound 5, the selenool intermediate is first reduced by sodium borohydride and citric acid system; the reaction solvent of the selenool intermediate and the compound 5 is acetonitrile, and cesium carbonate is used as a catalyst. Under N2 protection, the reaction is carried out at 65-70°C for 2-3 hours.

[0030] Furthermore, in the above technical solution, the preparation method of the selenool intermediate is as follows: the compound 8 is first reacted with anhydrous ethanol as solvent in the presence of NaBH4 for 10-20 min under N2 protection and 0±1℃ conditions, and then citric acid is added to continue the reaction for 5-8 min. The reaction solution is extracted with diethyl ether and water, the organic layer is washed with saturated NH4Cl aqueous solution and saturated NaCl, dried with Na2SO4, and the diethyl ether solvent is removed under reduced pressure to obtain the selenool intermediate.

[0031] Thirdly, the present invention provides an application of a selenium-substituted hemicyanine dye precursor in cell imaging and photodynamic cancer cell killing.

[0032] Fourthly, the present invention provides the application of a selenium-substituted hemicyanine dye parent in photodynamic bactericidal activity.

[0033] Beneficial effects:

[0034] This invention utilizes a single-atom substitution strategy to construct a selenium-substituted hemicyanine dye matrix. By controlling the dye's excited state and energy release process, the selenium-substituted hemicyanine dye matrix exhibits superior near-infrared absorption and emission spectral properties and high reactive oxygen species (ROS) generation capability. A hydroxyl active site is located at the other end of the dye matrix, which can be used to link biomarkers to substrates, thereby preparing an activatable photosensitive dye. This type of dye possesses good cell membrane permeability and can be successfully used for phototherapy to disinfect cancer cells and bacteria.

[0035] The selenium-substituted hemicyanine dye matrix of the present invention provides a new platform for constructing high-performance, reactivatable photosensitizer dyes. Based on this, more reactivatable dye photosensitizers can be developed successively. Cell-killing and antibacterial agents prepared based on this selenium-substituted hemicyanine dye matrix contain an effective dose of the selenium-substituted hemicyanine dye described in this invention and can be used for the elimination of experimental cancer cells and bacteria. Attached Figure Description

[0036] Figure 1 These are the UV-Vis absorption and fluorescence emission normalized spectra of the dye (10 μM) in methanol solvent according to Example 1 of this invention. The horizontal axis represents wavelength (nm), and the vertical axis represents normalized intensity. The excitation wavelength is 760 nm.

[0037] Figure 2 This is an evaluation of the reactive oxygen generation capability of the dye in Example 1 of the present invention. Specifically, a) shows the change in the UV-Vis absorption spectrum of the DPBF singlet oxygen scavenger after irradiation with a 760nm laser for different durations; b) shows the change in the UV-Vis absorption spectra of the DPBF singlet oxygen scavenger and the dye HCySe-OH after irradiation with a 760nm laser for different durations.

[0038] Figure 3 This is a cell imaging characterization of the dye in Example 1 of the present invention. Wherein, a) is a cell culture time of 0.5 h; b) is a cell culture time of 1 h; c) is a cell culture time of 2 h.

[0039] Figure 4 This is an verification of the generation of reactive oxygen species in cells by the dye in Example 1 of the present invention. Among them, a) is the control group and b) is the experimental group.

[0040] Figure 5 This refers to the staining of live / dead cells with the dye of Example 1 of this invention. Wherein, a) represents the green channel of the control group cells; b) represents the red channel of the control group cells; c) represents the green channel of the experimental group cells; and d) represents the red channel of the experimental group cells.

[0041] Figure 6 This is an example of the application of the dye in Embodiment 1 of the present invention for antibacterial purposes. Wherein, a) is the group without light, and b) is the group under light. Detailed Implementation

[0042] To better explain and facilitate understanding of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0043] To better understand the above technical solutions, exemplary embodiments of the present invention will be described in more detail below. It should be understood that the present invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a clearer and more thorough understanding of the present invention and to fully convey the scope of the invention to those skilled in the art.

[0044] This invention first provides a selenium-substituted hemicyanine dye parent material, having the general formula I structure:

[0045]

[0046] In general formula I:

[0047] R1 is H, C1-C 12 One of the alkyl groups, phenyl, p-phenylbenzyl chloride, p-phenylbenzyl bromide, SO3R4 or COOR4;

[0048] R2 can be C, S, or Se, with Se being preferred;

[0049] R3 is H, C1-C 12 One of the alkyl groups or a phenyl group, preferably H or phenyl;

[0050] R4 is H or C1-C 12 One of the alkyl groups;

[0051] Y can be Cl, Br, or I, with Br or I being preferred.

[0052] On the other hand, the method for preparing the selenium-substituted hemicyanine dye precursor provided by the present invention includes the following steps:

[0053] (1) Compound 3 was prepared by reacting compound 1 and compound 2 in a molar ratio of 1:3.0 to 5.0;

[0054]

[0055] (2) Compound 5 was prepared by reacting compounds 3 and 4 in a molar ratio of 2.0 to 2.5:1;

[0056]

[0057] (3) Compound 6 and compound 7 reacted in a molar ratio of 1:2.0 to 3.0 to prepare compound 8;

[0058]

[0059] (4) Compounds 5 and 8 react in a molar ratio of 1:1.2 to 1.5 to prepare compounds of general formula I.

[0060]

[0061] In a specific embodiment, the method for preparing the selenium-substituted hemicyanine dye precursor includes the following steps:

[0062] (1) Compounds 1 and 2 were added to acetonitrile solvent at a molar ratio of 1:3.0–5.0. The mixture was heated to reflux and the reaction progress was monitored (generally refluxed at 85–90 °C for 4–5 h). After the reaction was completed, the system was cooled to obtain a solid. The crude product was added to acetonitrile to form a supersaturated solution, which was then placed in a refrigerator at 4 °C for 12–14 h to obtain pure compound 3.

[0063] (2) Compounds 3 and 4 were added to a mixed solution of acetic acid, acetic anhydride, and triethylamine at a molar ratio of 2.0–2.5:1 (acetic acid:acetic anhydride:triethylamine volume ratio of 2–3:1:1), and reacted at 65–70 °C for 1–3 h. Subsequently, the solvent was removed under reduced pressure, followed by extraction three times with dichloromethane and saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, and the solvent was removed to obtain the crude product. Purification was achieved by column chromatography (eluent system: dichloromethane:methanol = 100:2–100:5) to obtain compound 5.

[0064] (3) Compounds 6 and 7 were added to dimethyl sulfoxide solvent at a molar ratio of 1:2.0–3.0 and stirred. Then, an appropriate amount of AgNO3 was added, and the mixture was reacted at 120–130 °C for 2–3 h. The solvent was removed under reduced pressure, and the mixture was extracted three times sequentially with dichloromethane and saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, and the solvent was removed to obtain the crude product. Compound 8 was obtained by column chromatography (eluent system: petroleum ether: ethyl acetate = 5:1–2:1) to give compound 8.

[0065] (4) Under N2 and 0℃ conditions, compound 8 was reacted with anhydrous ethanol in the presence of NaBH4 for 10-20 min, with a molar ratio of 1:3-4:5-7 for sodium borohydride and citric acid. Citric acid was then added and the reaction continued for 5-8 min to obtain the selenool intermediate. The reaction solution was diluted with diethyl ether and deionized water was added. The organic layer was washed with saturated NH4Cl aqueous solution and saturated NaCl, dried with Na2SO4, and the diethyl ether solvent was removed under reduced pressure. No further purification was required, and the solution could be used directly for subsequent reactions. Subsequently, compound 5, cesium carbonate (as a catalyst), and acetonitrile (as a solvent) were added sequentially and reacted at 65-70℃ for 2-3 h under N2 protection. After the reaction was completed, the solvent was removed under reduced pressure, and the solution was dissolved in dichloromethane. The solution was extracted with acidic saturated brine (100 mL saturated NaCl solution with 5 mL 10M hydrochloric acid), and the organic phase was collected. The solvent was removed to obtain the crude product. The compound of general formula I was obtained by purification using column separation technology (eluent system: dichloromethane: methanol = 100:2 to 100:7).

[0066] The following embodiments are intended to enable those skilled in the art to more fully understand the content of the present invention, but do not limit the present invention in any way.

[0067] Example 1

[0068] Synthesis of dye molecule HCySe-OH

[0069] The synthesis steps of the dye molecule HCySe-OH are as follows:

[0070]

[0071] Synthesis of Compound 3

[0072] Compounds 1 (5 g) and 2 (19.59 g) were added to acetonitrile solvent, heated to reflux while monitoring the reaction progress. After the reaction was complete, the system was cooled to obtain a solid. Recrystallization from acetonitrile yielded pure compound 3. The structure of compound 3 was characterized by NMR and high-resolution mass spectrometry.

[0073] 1 ¹H NMR (500MHz, DMSO-d⁶) δ: 8.08–7.91 (m, 1H), 7.86–7.81 (m, 1H), 7.68–7.57 (m, 2H), 4.49 (q, J = 7.3Hz, 2H), 2.83 (s, 3H), 1.53 (s, 6H), 1.44 (t, J = 7.3Hz, 3H). ESI-HRMS: m / z theoretical value C 13 H 18 N + [MI] - 188.1434; Measured value: 188.1438.

[0074] Synthesis of Compound 5

[0075] Compound 3 (2 g) and compound 4 (553 mg) were added to a mixed solution of acetic acid (14 mL), acetic anhydride (7 mL), and triethylamine (7 mL) and reacted at 65 °C for 2 h. The solvent was then removed under reduced pressure, followed by extraction three times with dichloromethane and saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, and the solvent was removed to obtain the crude product. Compound 5 was purified by column chromatography (eluent system: dichloromethane:methanol = 100:5) to obtain compound 5. The structure of compound 5 was characterized by NMR and high-resolution mass spectrometry.

[0076] 1H NMR(500MHz, DMSO-d6)δ:8.37(d,J=8.4Hz,2H),8.30(d,J=8.9Hz,2H),8.22(d,J=8.2Hz,2H),8.16(d,J=8.9Hz,2H),7.79(t,J= 7.6Hz,2H),7.73(t,J=7.5Hz,2H),4.62(q,J=7.4Hz,4H),2.94(s,6H),1.76(s,12H),1.50(t,J=7.3Hz,6H).ESI-HRMS:m / z theoretical value C 34 H 40 ClN2 + [MI] - 511.2875; Measured value: 511.2876.

[0077] Synthesis of Compound 8

[0078] Compound 6 (1 g) and compound 7 (603 mg) were added to dimethyl sulfoxide solvent and stirred. Then, an appropriate amount of AgNO3 was added, and the reaction was carried out at 120 °C for 2 h. The solvent was removed under reduced pressure, and the mixture was extracted three times sequentially with dichloromethane and saturated brine. The organic phase was collected, dried over anhydrous sodium sulfate, and the solvent was removed to obtain the crude product. Purification was performed using column chromatography (eluent system: petroleum ether: ethyl acetate = 2:1) to obtain compound 8. The structure of compound 8 was characterized by NMR and high-resolution mass spectrometry.

[0079] 1 H-NMR (400MHz, DMSO-d6) δ: 7.51 (dd, J=1.7, 1.0Hz, 1H), 7.50 (dd, J=1.7, 0.9Hz, 1H), 7.42 (t, J=2.0Hz, 2H), 7. 38(t,J=7.9Hz,2H),7.08(dd,J=2.3,1.0Hz,1H),7.06(dd,J=2.3,1.0Hz,1H),2.26(s,6H).ESI-HRMS: m / z theoretical value C 16 H 14 NaO4Se2 + [M+Na] + 452.9115; Measured value: 452.9128.

[0080] Synthesis of compound HCySe-OH

[0081] Compound 8 (96 mg) was dissolved in anhydrous ethanol (2 mL) under N2 and 0 °C. Sodium borohydride (23 mg) was added and reacted for 15 min, followed by the addition of citric acid (192 mg) and a further 5 min reaction, reducing compound 8 to a selenool intermediate. The obtained selenool intermediate was extracted with diethyl ether (5 mL) and deionized water (3 mL), and the organic phase was collected. The organic phase was washed with saturated NH4Cl aqueous solution and saturated NaCl, dried over Na2SO4, and the diethyl ether solvent was removed under reduced pressure. No further purification was required, and the intermediate was used directly in subsequent reactions. Subsequently, compound 5 (100 mg), carbonic acid (203 mg), and acetonitrile (as solvent) were added sequentially, and the reaction was carried out under N2 protection at 65 °C for 2 h. After the reaction was complete, the solvent was removed under reduced pressure, and the product was dissolved in dichloromethane. Extraction was performed with acidic saturated brine, and the organic phase was collected. The solvent was removed to obtain the crude product. Purification was performed using column chromatography (eluent system: dichloromethane:methanol = 100:7) to obtain compounds of general formula I. The structure of the compound was characterized by NMR and high-resolution mass spectrometry.

[0082] 1 H NMR(400MHz,Methylene Chloride-d2)δ:8.12(d,J=13.8Hz,1H),7.72(s,1H),7.56-7.44(m,3H),7.39( t,J=7.4Hz,1H),7.26(d,J=7.8Hz,1H),7.22(s,1H),7.13-7.04(m,1H),6.29(d ,J=13.8Hz,1H),4.17(q,J=7.3Hz,2H),2.78(t,J=6.0Hz,2H),2.60(t,J=6.2Hz ,2H),2.01-1.86(m,2H),1.77(s,6H),1.47(t,J=7.1Hz,3H).ESI-HRMS:m / z theoretical value C 27 H 28 NOSe + [M+Na] + 462.1331; Measured value 462.1330.

[0083] Example 2

[0084] The dye HCySe-OH molecule synthesized in Example 1 was dissolved in dimethyl sulfoxide to prepare a dye mother liquor. A certain volume of the mother liquor was then dissolved in methanol to prepare a 10 mM dye solution. UV-Vis absorption and fluorescence spectra were then collected using an Agilent UV-Vis spectrophotometer and a fluorescence spectrophotometer, respectively. The tests revealed that the maximum absorption wavelength and maximum emission wavelength of the dye in methanol solvent were approximately 760 nm and 784 nm, respectively. Figure 1 ).

[0085] Example 3

[0086] A methanol solution containing DPBF (DPBF is a commonly used reactive oxygen species scavenger; its absorption peak at 410 nm is significantly reduced in the presence of singlet oxygen) and the dye HCySe-OH was placed under a 760 nm laser and irradiated for different time periods (0-60 s). The spectra were collected using a UV-Vis spectrophotometer and plotted. Figure 2 a) A methanol solution containing DPBF was placed under a 760 nm laser for different time periods (0-60 s). The absorbance at 410 nm was collected using a UV-Vis spectrophotometer, and the results are plotted as follows. Figure 2 b). This indicates that the dye HCySe-OH has a good ability to generate reactive oxygen species.

[0087] Example 4

[0088] Human breast cancer cells (MCF-7) were seeded into confocal microscopy dishes and cultured in a cell culture incubator (37°C, 5% CO2). When the cell density reached a suitable level, the dye HCySe-OH synthesized in Example 1 was added, and the cells were cultured for different time periods (0.5, 1.0, and 2.0 h). The cells were then imaged using a laser confocal microscope. The excitation wavelength was 639 nm, and the receiving wavelength was 700-730 nm. The imaging results are shown below. Figure 3 As described in a)-3c), the fluorescence intensity increases with the extension of cell culture time, indicating that the dye can easily enter the cells and can be used for live cell fluorescence imaging.

[0089] Example 5

[0090] Human breast cancer cells MCF-7 were seeded into confocal microscopy dishes and cultured in a cell culture incubator (37℃, 5% CO2). When the cell density was suitable, the commercially available DCFH-DA reactive oxygen species probe was added to the confocal cell culture dishes and incubated for 2 hours. Then, the dye HCySe-OH synthesized in Example 1 was added, and the cells were cultured for another 1 hour. The confocal microscopy dishes containing the cells were divided into two groups: a control group (dark group, no light exposure) and a light-exposed group (760nm laser irradiation for 10 minutes). Finally, the results of laser confocal microscopy imaging of the cells in different groups showed that the cells in the control group did not exhibit obvious green fluorescence. Figure 4 a)); The cells in the experimental group showed obvious green fluorescence ( Figure 4 b) Imaging results demonstrate that the dye HCySe-OH synthesized in Example 1 can generate reactive oxygen species within cells. The excitation wavelength was 488 nm, and the receiving wavelength was 510-530 nm.

[0091] Example 6

[0092] Human breast cancer cells MCF-7 were seeded into confocal microscopy dishes and cultured in a cell culture incubator (37℃, 5% CO2). When the cell density was suitable, the dye HCySe-OH synthesized in Example 1 was added, and the cells were cultured for another 1 hour. The confocal microscopy dishes containing the cells were divided into two groups: a control group (dark group, no light exposure) and a light-exposed group (760nm laser irradiation for 10 min). Cells treated as described above were then treated with a live / dead cell kit (Calcein-AM and Propidium Iodide). Finally, laser confocal microscopy imaging of the cells from different groups showed that the cells in the control group exhibited significant fluorescence in the green channel but no fluorescence in the red channel. Figure 5 a) and 5b); no obvious fluorescence was observed in the green channel of the cells in the experimental group, while obvious fluorescence was observed in the red channel. Figure 5 c) and 5d)). Calcein-AM / PI cell double staining imaging results showed that the reactive oxygen species generated by the dye HCySe-OH during light treatment could effectively kill MCF-7 cells. Green channel: excitation wavelength 488nm, receiving band 510-530nm; red channel: excitation wavelength 543nm, receiving band 569-700nm.

[0093] Example 7

[0094] The dye HCySe-OH molecule synthesized in Example 1 was mixed with Staphylococcus aureus and incubated for 1 hour, followed by incubation with a 760 nm laser (50 mW / cm²). 2 Irradiate for 10 minutes, then spread onto plates. The petri dishes are then incubated at 37℃ for 24 hours. The other group (no light group) differs from the above experimental groups only in that no light treatment is applied; all other conditions are the same. Bacterial plate results show that compared to... Figure 6 a), Figure 6 The extremely low bacterial colony count in b) indicates that the reactive oxygen species produced by the dye have antibacterial effects.

[0095] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for the synthesis of a selenium-substituted hemicyanine dye precursor, characterized in that, The hemicyanine dye precursor structure is shown as general formula I: In general formula I: R1is H, phenyl, p-phenylbenzyl chloride, p-phenylbenzyl bromide, SO3R4, COOR4, or one of the group of C1-C 12 alkyl; R2is H, C1-C4alkyl, or C1-C4alkoxy; R2 is Se; R3 is one of H, phenyl; R4is H or one of C1-C 12 one of alkyl; Y is Br or I; The synthesis method of the selenium-substituted hemicyanine dye precursor comprises the following steps: (1) Compound 1 and compound 2 are reacted according to a molar ratio of 1:3.0-5.0 to prepare compound 3; (2) Compound 3 and compound 4 are reacted according to a molar ratio of 2.0-2.5:1 to prepare compound 5; (3) Compound 6 and compound 7 are reacted according to a molar ratio of 1:2.0-3.0 to prepare compound 8; In step (3), the solvent for the reaction of compound 6 and compound 7 is dimethyl sulfoxide, AgNO3 is used as the catalyst, and the reaction condition is 120~130 o C for 2~3 h; (4) Compound 5 and compound 8 are reacted according to a molar ratio of 1:1.2-1.5 to prepare the compound of general formula I.

2. The method of synthesis of selenium-substituted hemicyanine dye precursor according to claim 1, characterized in that, In step (1), the reaction solvent of the compound 3 and the compound 4 is acetonitrile, and the reaction condition is 85~90 o C reacts for 4~5 h.

3. The method of synthesis of selenium substituted hemicyanine dye precursor according to claim 1, characterized in that, In step (2), the reaction solvent of the compound 3 and the compound 4 is a mixed solution of acetic acid, acetic anhydride and triethylamine, and the reaction condition is 65~70 o C reacts for 1~3 h.

4. The method of synthesis of selenium substituted hemicyanine dye parents according to claim 1, characterized in that, In step (4), the compound 8 is reduced with sodium borohydride and citric acid system before reacting with the compound 5; the reaction solvent of the selenol intermediate with the compound 5 is acetonitrile, with cesium carbonate as the catalyst, under N2protection, at 65~70 o C reacts for 2~3 h.

5. The method of synthesis of selenium-substituted hemicyanine dye precursor according to claim 4, characterized in that, The method for preparing the selenol intermediate is that the compound 8 is reacted in the presence of NaBH4 in anhydrous ethanol as a solvent under N2 protection and 0±1 o C conditions for 10-20 min, then citric acid is added to continue the reaction for 5-8 min, the reaction solution is extracted with diethyl ether and water, the organic layer is washed with saturated NH4Cl aqueous solution and saturated NaCl, dried over Na2SO4, and the diethyl ether solvent is removed under reduced pressure to obtain the selenol intermediate.

6. The selenium-substituted hemicyanine dye precursor of claim 1 is applied in photodynamic bactericidal.

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