CN110790698A - Deep red/near infrared multifunctional aggregation-induced emission material and preparation method and application thereof - Google Patents
Deep red/near infrared multifunctional aggregation-induced emission material and preparation method and application thereof Download PDFInfo
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- CN110790698A CN110790698A CN201910784053.XA CN201910784053A CN110790698A CN 110790698 A CN110790698 A CN 110790698A CN 201910784053 A CN201910784053 A CN 201910784053A CN 110790698 A CN110790698 A CN 110790698A
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- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention relates to a deep red/near infrared multifunctional aggregation-induced emission material, a preparation method and application thereof. The pyridine ring in the molecular structure of the deep red/near infrared multifunctional aggregation-induced emission material provided by the invention enables the molecules to have electropositivity, and meanwhile, the molecules have proper lipid-water partition coefficient (3< ClogP <5) and space structure, thereby being beneficial to combining with gram-positive bacteria. When the molecule disclosed by the invention is co-cultured with bacteria, the specific 'lightening' imaging of gram-positive bacteria can be realized; the strong electron-donating (D) -electron-withdrawing (A) effect of the molecule itself causes the red shift of the absorption and emission wavelength of the molecule, and has deep red/near infrared fluorescence emission and strong ROS generation capacity. Meanwhile, the aggregation-induced emission material provided by the invention can efficiently kill gram-positive bacteria.
Description
Technical Field
The invention relates to the technical field of multifunctional organic micromolecule synthesis, in particular to a deep red/near infrared multifunctional aggregation-induced emission material, and a preparation method and application thereof.
Background
Fluorescence imaging technology has become an indispensable tool in disease research, medical practice and clinical experiments due to its advantages of high sensitivity, fast response, high spatial-temporal resolution, simple operation and non-invasiveness. More importantly, the fluorescence imaging technology can be used as a visual tool to perform nondestructive in-situ real-time tracking on a research target, and has natural advantages for timely and rapid detection and identification of pathogenic bacteria such as bacteria and the like.
The development of a simple and quick novel antibacterial system which is not influenced by bacterial drug resistance has important significance for overcoming the bacterial drug resistance and improving the antibacterial effect. Photodynamic Therapy (PDT) has received increasing attention from researchers at home and abroad in recent years. Compared with antibiotics with specific action targets, active oxygen generated by the photosensitizer can generate toxic action on bacteria both outside and inside the bacteria, and the photosensitizer does not need to penetrate through bacterial cell membranes to enter the inside of the bacteria, so that the antibacterial agent has a different sterilization mechanism from the traditional antibiotics. Meanwhile, photodynamic antibiosis is an oxidation damage mechanism based on synergistic effect of three factors of light, photosensitizer and oxygen, so that the problem of drug resistance caused by single drug, concentration of the photosensitizer, insufficient exposure time and the like is avoided.
Based on a fluorescence imaging technology and a photodynamic antibacterial principle, a one for all multifunctional system with gram-positive bacteria detection and photodynamic antibacterial functions is developed, in fact, as a core of photodynamic sterilization, most photosensitizers have fluorescence emission properties and have the capability of being used for fluorescence imaging mediated sterilization, however, most photosensitizers are hydrophobic, and are easy to form aggregates after being contacted with bacteria in a physiological environment, and are influenced by aggregation-induced quenching (ACQ) effect, so that the problems of reduced fluorescence intensity and reduced generation efficiency of active oxygen are easy to occur, and the photodynamic sterilization effect is lower.
Currently, aggregation-induced emission materials have some applications in the bacterial field, and there are few aggregation-induced emission materials with both gram-positive bacteria selective imaging and photodynamic killing capabilities. The near-infrared luminescent fluorescent molecule has many advantages in biological application, such as strong penetrating power and less light damage to organisms, can avoid interference of autofluorescence of the organisms on signal collection, and can greatly reduce light scattering. However, no report is found on the diagnosis and treatment integrated deep red/near infrared aggregation induced luminescent material which integrates gram-positive bacteria selective imaging and photodynamic antibacterial capability at present; other deep red/near infrared aggregation-induced emission molecules have been reported less frequently, and in few reported examples, the synthesis route thereof is complicated, and several reactions and complicated separation and purification steps are usually required.
Accordingly, the prior art is yet to be improved and developed.
Disclosure of Invention
In view of the above-mentioned shortcomings of the prior art, the present invention aims to provide an aggregation-induced emission material with deep red/near infrared emission, a preparation method thereof and applications thereof in gram-positive bacteria imaging and photodynamic sterilization, and aims to solve the problem of complex synthesis route of the existing near infrared emission aggregation-induced emission material.
The technical scheme adopted by the invention for solving the technical problems is as follows:
in a first aspect, a deep red/near infrared multifunctional aggregation-induced emission material is selected from any one of molecular structural formulas (I) - (IV):
wherein R is1、R2Each independently selected from H,
One of (1);
X-independently selected from I-、PF6 -、BF4 -、SbF6 -、SbF5 -、CH3COO-、CF3COO-、CO3 2-、SO4 2-、 SO3 2-、CF3SO2 -、TsO-、ClO4 -、F-、Cl-、Br-、(F3CSO2)N-、PO4 3-One kind of (1).
A preparation method of the deep red/near infrared multifunctional aggregation-induced emission material with the molecular structural formula (I) comprises the following steps:
step 11, adding 4- (diphenylamino) benzaldehyde and 1, 4-dimethylpyridine-1-iodide into a reaction vessel, adding absolute ethyl alcohol under the protection of nitrogen, adding piperidine as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring a reaction solution into absolute ethyl ether to obtain orange solid powder;
step 12, dissolving the orange solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain orange solid TPy, wherein the molecular structural formula of TPy is
Preferably, in the preparation method of the aggregation-induced emission material, the first reaction condition is a temperature of 70-85 ℃.
A preparation method of the deep red/near infrared multifunctional aggregation-induced emission material with the molecular structural formula (II) comprises the following steps:
step 21, adding 4-bromotriphenylamine, 4-formylphenylboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate into a reaction vessel, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating after the reaction to obtain a first intermediate product;
step 22, mixing the first intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring the reaction solution into absolute ethyl ether to obtain first red solid powder;
step 23, dissolving the first red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain a first red solid TPPy, wherein the molecular structural formula of the TPPy is shown in the specification
Preferably, in the preparation method of the deep red/near infrared multifunctional aggregation-induced emission material, the second reaction condition is reflux reaction at a temperature of 60-80 ℃ for 15-18 hours.
A preparation method of the deep red/near infrared multifunctional aggregation-induced emission material with the molecular structural formula (III) comprises the following steps:
step 31, mixing 4-bromotriphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a second intermediate product after the reaction;
step 32, mixing the second intermediate product and 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into the anhydrous ether to obtain second red solid powder;
step 33, dissolving the second red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring at 25 ℃ for 0.5-2 hours, and filtering to obtain a second red solid TTPy, wherein the molecular structural formula of the TTPy is shown in the specification
A preparation method of the deep red/near infrared multifunctional aggregation-induced emission material with the molecular structural formula (IV) comprises the following steps:
step 41, mixing 4-bromo-4 ',4' -dimethoxy triphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a third intermediate product after the reaction;
step 42, mixing the third intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into anhydrous ether to obtain third red solid powder;
step 43, dissolving the third red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain a third red solid MeOTTPy, wherein the molecular structural formula of the MeOTTPy is
Preferably, in the preparation method of the deep red/near infrared multifunctional aggregation-induced emission material, the volume ratio of toluene to methanol in the mixed solvent of toluene and methanol is 1: 1.
The application of the deep red/near infrared multifunctional aggregation-induced emission material is used for gram-positive bacteria specific marking and/or gram-positive bacteria dynamic killing.
Preferably, the deep red/near infrared multifunctional aggregation-induced emission material is applied to bacteria, including gram-positive bacteria and gram-negative bacteria.
Has the advantages that: the deep red/near infrared multifunctional aggregation-induced emission material provided by the invention has a simple synthesis method and does not need complex synthesis steps. Meanwhile, the material has longer absorption and emission wavelength, and the emission wavelength can reach a near infrared region. Has very high selectivity for gram-positive bacteria and good biocompatibility. Has high active oxygen (ROS) generation efficiency, and can effectively kill gram-positive bacteria.
Drawings
FIG. 1a is a normalized UV absorption spectrum of TPy, TPPy, TTPy, MeOTTPy in DMSO solution.
FIG. 1b is the fluorescence emission spectrum of MeOTTPy (10. mu.M) in DMSO/Toluene (v/v) mixed solvent with increasing Toluene (Toluene) content, lambdaex＝500nm。
FIG. 1c shows the fluorescence enhancement factor of TPy, TPPy, TTPy, MeOTTPy (10. mu.M) in DMSO/Toluene (v/v) mixed solvent with increasing Toluene (Toluene) content, lambdaex＝500nm。
FIG. 1d shows fluorescence emission spectra of TPy, TPPy, TTPy, and MeOTTPy normalized in the solid state.
FIG. 2 is a CLSM plot of TPy, TPPy, TTPy, MeOTTPy (2. mu.M) incubated with E.coli and S.aureus, respectively, for 20 minutes.
FIG. 3 is a CLSM plot of TPy, TPPy, TTPy, MeOTTPy (2. mu.M) incubated with P.aeruginosa and E.faecalis, respectively, for 20 minutes.
FIG. 4a shows the white light (22.1mW cm)-2) The irradiation time was prolonged, and the fluorescence intensity of the mixed solution of TPy, TPPy, TTPy, MeOTTPy (50nM) and ROS indicator DCFH (10. mu.M) was enhanced by a factor of two.
FIG. 4b shows the white light (22.1mW cm)-2) The irradiation time was extended and the fluorescence intensity of the mixture of TTPy (1. mu.M) and ROS indicator DCFH (5. mu.M) was increased by a factor of two.
FIGS. 5a and 5b show the presence/absence of TTPy (2. mu.M) and/or white light (60 mWcm) of Escherichia coli and Staphylococcus aureus, respectively-2) A photograph of the colonies from the agar plate under the condition treatment and a statistical chart of the number of the corresponding colonies.
FIG. 5c shows Staphylococcus aureus in the presence/absence of TTPy (2. mu.M) and/or white light (60mW cm)-2) Scanning electron microscopy images under conditioned conditions.
FIG. 6a first and second rows of S.aureus infected rat wounds with/without TTPy (2. mu.M) and/or white light (60mW cm)-2) Photographs of the wound on the first and fourth days after conditioning; third and fourth rowsThe rows are HE staining and partial magnification of wound tissue sections on day four, respectively.
FIGS. 6b and 6c are photographs of colonies on agar plates coated with the homogeneous suspension of the wound tissue shown in the photograph of FIG. 6a for 14 to 16 hours, respectively, and statistical charts of the numbers of corresponding colonies.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention clearer and clearer, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The molecular structural formula of the deep red/near infrared multifunctional aggregation-induced emission material provided by the embodiment of the invention is one of the following:
specifically, wherein R1、R2Each independently selected from H,
X-Independently selected from I-、PF6 -、BF4 -、SbF6 -、SbF5 -、CH3COO-、CF3COO-、CO3 2-、SO4 2-、SO3 2-、 CF3SO2 -、TsO-、ClO4 -、F-、Cl-、Br-、(F3CSO2)N-、PO4 3-。
The pyridine ring in the molecular structure of the deep red/near infrared multifunctional aggregation-induced emission material carries a certain positive charge, the surface of bacteria has electronegativity, and the electropositive aggregation-induced emission molecules are easy to aggregate on the surface of the bacteria due to the electrostatic interaction between the positive charge and the negative charge, so that the precondition is provided for the selective imaging of gram-positive bacteria; since the cell membrane of the bacteria is composed of phospholipid bilayers, the appropriate lipid-water partition coefficient (3< ClogP <5) enables the aggregation-inducing luminescent molecule to be capable of the cell membrane of the bacteria, limits the movement of the aggregation-inducing luminescent molecule, and emits fluorescence; due to the difference of the envelope structures of gram-positive bacteria and gram-negative bacteria, the aggregation-induced emission molecule disclosed by the invention is easier to insert into the cell membrane of the gram-positive bacteria during the co-culture with the bacteria, so that the specific 'lightening' imaging of the gram-positive bacteria is realized.
Based on the same inventive concept, the invention also provides a preparation method of the deep red/near infrared multifunctional aggregation-induced emission material, which comprises the following preparation steps:
step 11, adding 4- (diphenylamino) benzaldehyde and 1, 4-dimethylpyridine-1-iodide into a reaction vessel, adding absolute ethyl alcohol under the protection of nitrogen, adding piperidine as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring a reaction solution into absolute ethyl ether to obtain orange solid powder; the first reaction condition is that the temperature is 70-85 DEG C
Step 12, dissolving the orange solid powder in acetone and mixing with saturated potassium hexafluorophosphate water solution, stirring at 25 ℃ for 0.5-2 hours, and filtering to obtain an orange solid TPy.
The synthetic route is as follows:
specifically, 4- (diphenylamino) benzaldehyde (54.6mg, 0.20mmol) and 1, 4-dimethylpyridine-1-iodide (56.4mg, 0.24mmol) were weighed into a 50mL two-necked flask. Under the protection of nitrogen, 15mL of absolute ethyl alcohol is added as a reaction solvent, a few drops of piperidine is added as a catalyst, and the mixture is refluxed and reacted at 78 ℃ overnight. After the reaction is finished, cooling to room temperature, pouring the reaction liquid into anhydrous ether, and obtaining orange solid powder after precipitation and filtration.
Redissolving the solid powder in acetone and mixing with saturated KPF6Aqueous (3 mL) potassium hexafluorophosphate was mixed well. After stirring at room temperature for 1 hour, acetone was evaporated using a nitrogen purge. Filtration, washing with water and drying under reduced pressure gave an orange solid. With DCM/CH3OH (v/v,99/1) was used as an eluting solvent, and was purified and separated by a 100-200 mesh neutral alumina column to give TPy (87.0mg) as an orange powder in 86.0% yield. Product nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,DMSO-d6)δ:8.78(d,J＝6.6Hz, 2H),8.13(d,J＝6.6Hz,2H),7.94(d,J＝16.2Hz,1H),7.64-7.59(m, 2H),7.38(t,J＝7.8Hz,4H),7.29(d,J＝16.3Hz,1H),7.17(d,J＝7.3Hz,2H),7.14-7.09(m,4H),6.95(d,J＝8.6Hz,2H),4.21(s,3H)。13C NMR(100MHz,DMSO-d6)δ:152.85,149.49,146.24,144.83,140.54, 129.89,129.70,128.02,125.44,124.54,122.95,120.75,120.51,46.70。 ESI HRMS:C26H23N2[M-PF6]+calculated value of 363.1856 and actual measured value of 363.1822.
TPy normalized UV absorption spectra in DMSO solution as shown in FIG. 1 a. As shown in FIG. 1c, the fluorescence enhancement factor of TPy in the DMSO/Toluene (v/v) mixed solvent is increased with the increase of Toluene (Toluene) content, lambda ex500 nm. FIG. 1d is TPy normalized fluorescence emission spectra in the solid state.
In another embodiment, the preparation method of the deep red/near infrared multifunctional aggregation-induced emission material comprises the following preparation steps:
step 21, adding 4-bromotriphenylamine, 4-formylphenylboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate into a reaction vessel, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating after the reaction to obtain a first intermediate product; the second reaction condition is reflux reaction at 60-80 deg.c for 15-18 hr.
Step 22, mixing the first intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring the reaction solution into absolute ethyl ether to obtain first red solid powder;
and step 23, dissolving the first red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at the temperature of 25 ℃, and filtering to obtain a first red solid TPPy.
The synthetic route is as follows:
specifically, (1) Synthesis of Compound 1
Weighing 4-bromotriphenylamine (50.0mg, 0.15mmol), 4-formylphenylboronic acid (30.0mg, 0.20mmol) and [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (11.3mg, 0.02mmol) and potassium carbonate (106.6mg, 0.77mmol) were added to a 50mL two-necked flask. Under the protection of nitrogen, the reaction solution is added with the following components in a ratio of 1: 20mL of a mixed solvent of toluene and methanol was added as a reaction solvent at a volume ratio of 1, and the reaction was refluxed at 75 ℃ for 16 hours. After the reaction is finished, the reaction solvent is removed by reduced pressure rotary evaporation, 100mL of dichloromethane is added as an organic phase, the organic phase is washed by water and saturated sodium chloride in sequence, the organic phase is dried by anhydrous sodium sulfate overnight, and the crude product is obtained after reduced pressure rotary drying. Purification and isolation through 200-mesh 300-mesh silica gel column gave Compound 1(48.8mg) as a bright yellow solid in 93.2% yield. Nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,CDCl3)δ:10.01(s,1H),7.93 (d,J＝8.4Hz,2H),7.73(d,J＝8.4Hz),7.52(d,J＝8.4Hz,2H),7.28 (t,J＝8.0Hz,4H),7.15(m,6H),7.07(t,J＝7.2Hz,2H)。ESI HRMS:C25H19NO [M]+calculated value of 349.1466 and actual measured value of 349.1464.
(2) Synthesis of Compound TPPy
Compound 1(50.0mg, 0.14mmol) and 1, 4-dimethylpyridine-1-iodide (40.0mg, 0.17mmol) were weighed into a 50mL two-necked flask. Under the protection of nitrogen, 15mL of absolute ethyl alcohol is added as a reaction solvent, a few drops of piperidine is added as a catalyst, and the mixture is refluxed and reacted at 78 ℃ overnight. To be treatedAfter the reaction is finished, cooling to room temperature, pouring the reaction liquid into anhydrous ether, and obtaining red solid powder after precipitation and filtration. Redissolving the solid powder in acetone and mixing with saturated KPF6The aqueous solution (2.1mL) was mixed well. After stirring at room temperature for 1 hour, acetone was evaporated using a nitrogen purge. Filtration, washing with water and drying under reduced pressure gave a red solid. Purification and separation were carried out by means of a 100-mesh 200-mesh neutral alumina column to obtain the compound TPPy (63.9mg) as a red powder in a yield of 78.1%. Nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,DMSO-d6)δ:8.85(d,J＝6.4Hz,2H),8.21(d,J＝6.4Hz,2H),8.03(d,J＝16.3Hz, 1H),7.85-7.76(m,4H),7.72-7.67(m,2H),7.54(d,J＝16.3Hz,1H), 7.36-7.30(m,4H),7.11-7.03(m,8H),4.25(s,3H)。13C NMR(100MHz,DMSO-d6) δ:147.34,146.85,145.06,140.21,133.65,132.51,129.66,128.80, 127.66,126.57,124.42,123.53,123.43,122.87,122.81,46.87。ESI HRMS: C32H27N2[M-PF6]+calculated value of 439.2169 and actual measured value of 439.2167.
Normalized uv absorption spectra of TPPy in DMSO solution as shown in figure 1 a. As shown in FIG. 1c, the fluorescence enhancement factor in DMSO/Toluene (v/v) mixed solvent, λ, increases with increasing Toluene (Toluene) content of TPPy ex500 nm. FIG. 1d shows the fluorescence emission spectrum of TPPy normalized to that in the solid state.
In another embodiment, the preparation method of the deep red/near infrared multifunctional aggregation-induced emission material comprises the following preparation steps:
step 31, mixing 4-bromotriphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a second intermediate product after the reaction;
step 32, mixing the second intermediate product and 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into the anhydrous ether to obtain second red solid powder;
and step 33, dissolving the second red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain second red solid TTPy.
The synthetic route is as follows:
(1) synthesis of Compound 2
Weighing 4-bromotriphenylamine (50.0mg, 0.15mmol), 5-aldehyde-2-thiopheneboronic acid (31.3mg, 0.20mmol) and [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (11.3mg, 0.02mmol) and potassium carbonate (106.6mg, 0.77mmol) were added to a 50mL two-necked flask. Under the protection of nitrogen, the reaction solution is added with the following components in a ratio of 1: 20mL of a mixed solvent of toluene and methanol was added as a reaction solvent at a volume ratio of 1, and the reaction was refluxed at 75 ℃ for 16 hours. After the reaction is finished, the reaction solvent is removed by reduced pressure rotary evaporation, 100mL of dichloromethane is added as an organic phase, the organic phase is washed by water and saturated sodium chloride in sequence, the organic phase is dried by anhydrous sodium sulfate overnight, and the crude product is obtained after reduced pressure rotary drying. Purification and isolation through 200-mesh 300-mesh silica gel column using PE/DCM (v/v,2/1) as the eluting solvent gave compound 2(48.6mg) as a bright yellow solid in 91.3% yield. Nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,CDCl3)δ:9.85(s,1H),7.71(d,J＝4Hz,1H),7.52(d,J＝8.8 Hz,2H),7.28-7.32(m,5H),7.05-7.15(m,8H)。ESI HRMS:C23H17NOS[M]+calculated value of 355.1031 and actual measured value of 355.1011.
(2) Synthesis of TTPy Compound
Compound 2(40.0mg, 0.11mmol) and 1, 4-dimethylpyridine-1-iodide (30.6mg, 0.13mmol) were weighed into a 50mL two-necked flask. Under the protection of nitrogen, 15mL of absolute ethyl alcohol is added as a reaction solvent, a few drops of piperidine is added as a catalyst, and the mixture is refluxed and reacted at 78 ℃ overnight. After the reaction is finished, cooling to room temperature, pouring the reaction liquid into anhydrous ether, and obtaining red solid powder after precipitation and filtration. Redissolving the solid powderDissolving in acetone and reacting with saturated KPF6The aqueous solution (1.6mL) was mixed well. After stirring at room temperature for 1 hour, acetone was evaporated using a nitrogen purge. Filtration, washing with water and drying under reduced pressure gave a red solid. Purified and separated by a 100-mesh 200-mesh neutral alumina column to obtain the red powder compound TTPy (56.1mg) with the yield of 86.4 percent. Nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,DMSO-d6)δ:8.79(d,J＝6.8Hz,2H),8.14-8.21(m,3H),7.62(d,J＝6 8.8Hz,2H), 7.50(d,J＝2.0Hz,2H),7.35(t,J＝8.0Hz,2H),7.07-7.14(m,7H), 6.98(d,J＝8.8Hz,2H),4.22(s,3H)。13CNMR(100MHz,DMSO-d6)δ:152.22, 147.83,147.20,146.57,144.82,138.68,133.75,129.78,126.84,126.32, 124.78,124.21,123.93,122.95,122.23,121.22,46.75。ESIHRMS:C30H25N2S [M-PF6]+calculated value of 445.1733 and actual measured value of 445.1741. Normalized uv absorption spectrum of TTPy in DMSO solution as shown in figure 1 a. As shown in FIG. 1c, the fluorescence enhancement factor in DMSO/Toluene (v/v) mixed solvent, λ, increases with increasing Toluene (Toluene) content of TTPy ex500 nm. FIG. 1d is the fluorescence emission spectrum normalized by TTPy in the solid state.
In another embodiment, the preparation method of the deep red/near infrared multifunctional aggregation-induced emission material comprises the following preparation steps:
step 41, mixing 4-bromo-4 ',4' -dimethoxy triphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a third intermediate product after the reaction;
step 42, mixing the third intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into anhydrous ether to obtain third red solid powder;
and step 43, dissolving the third red solid powder in acetone, mixing with a saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at the temperature of 25 ℃, and filtering to obtain a third red solid MeOTTPy.
The synthetic route is as follows:
specifically, (1) Synthesis of Compound 3
Weighing 4-bromo-4 ',4' -dimethoxy triphenylamine (50.0mg, 0.13mmol), 5-aldehyde-2-thiopheneboronic acid (26.5mg, 0.17mmol) and [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride (11.3mg, 0.02mmol) and potassium carbonate (90.0mg, 0.65mmol) were added to a 50mL two-necked flask. Under the protection of nitrogen, the reaction solution is added with the following components in a ratio of 1: 20mL of a mixed solvent of toluene and methanol was added as a reaction solvent at a volume ratio of 1, and the reaction was refluxed at 75 ℃ for 16 hours. After the reaction is finished, the reaction solvent is removed by reduced pressure rotary evaporation, 100mL of dichloromethane is added as an organic phase, the organic phase is washed by water and saturated sodium chloride in sequence, the organic phase is dried by anhydrous sodium sulfate overnight, and the crude product is obtained after reduced pressure rotary drying. Purification and separation were carried out with 200-300 mesh silica gel column using PE/EA (v/v,3/1) as an elution solvent to obtain Compound 3(50.9mg) as a red solid in a yield of 94.4%. Nuclear magnetic and mass spectral characterization was as follows:1HNMR(400MHz,CDCl3)δ:9.83(s,1H),7.69(d,J＝4Hz,1H), 7.46(d,J＝9.2Hz,2H),7.25(d,J＝4.8Hz,1H),7.10-7.08(m,4H), 6.91-6.85(m,6H),3.81(s,6H)。13C NMR(100MHz,CDCl3):182.47,156.51, 155.06,149.98,140.78,139.85,137.79,127.19,127.11,124.21,122.27, 119.23,114.85,55.46.ESI HRMS:C25H21NO3S[M]+calculated value of 415.1242 and actual measured value of 415.1248.
(2) Synthesis of Compound MeOTTPy
Compound 3(50.0mg, 0.12mmol) and 1, 4-dimethylpyridine-1-iodide (33.0mg, 0.14mmol) were weighed into a 50mL two-necked flask. Under the protection of nitrogen, 15mL of absolute ethyl alcohol is added as a reaction solvent, a few drops of piperidine is added as a catalyst, and the mixture is refluxed and reacted at 78 ℃ overnight. After the reaction is finished, cooling to room temperature, pouring the reaction liquid into anhydrous ether, precipitating and filtering to obtain the productTo a red solid powder. Redissolving the solid powder in acetone and mixing with saturated KPF6The aqueous solution (1.7mL) was mixed well. After stirring at room temperature for 1 hour, acetone was evaporated using a nitrogen purge. Filtration, washing with water and drying under reduced pressure gave a red solid. Purification and separation were carried out by means of a 100-mesh 200-mesh neutral alumina column to obtain the compound MeOTTPy (65.7mg) as a red powder in a yield of 84.2%. Nuclear magnetic and mass spectral characterization was as follows:1H NMR(400MHz,DMSO-d6): 8.76(d,J＝6.8Hz,2H),8.12-8.19(m,3H),7.53(d,J＝8.8Hz,2H), 7.43-7.47(m,2H),7.06-7.10(m,5H),6.94-6.96(m,4H),6.77(d,J＝8.8 Hz,2H),4.2(s,3H),3.76(s,6H)。13C NMR(100MHz,DMSO-d6):156.24, 152.23,148.96,147.80,144.70,139.26,138.00,133.86,133.83,127.26, 126.63,123.98,123.39,122.79,120.75,118.41,115.07,55.25,46.66。 ESI HRMS:C32H29N2O2S[M-PF6]+calculated value of 505.1950 and actual measured value of 505.1931.
Normalized uv absorption spectra of MeOTTPy in DMSO solution as shown in figure 1 a. As shown in FIG. 1c, the fluorescence enhancement factor of MeOTTPy (10. mu.M) in DMSO/Toluene (v/v) mixed solvent is increased with the Toluene (Toluene) content, lambda ex500 nm. FIG. 1b is the fluorescence emission spectrum of MeOTTPy (10. mu.M) in DMSO/Toluene (v/v) mixed solvent with increasing Toluene (Toluene) content, lambda ex500 nm. FIG. 1d is the fluorescence emission spectrum of MeOTTPy normalized in the solid state.
Based on the same inventive concept, the invention also provides application of the deep red/near infrared multifunctional aggregation-induced emission material for gram-positive bacteria specific marking and/or gram-positive bacteria photodynamic killing.
Specifically, the pyridine ring of the deep red/near infrared multifunctional aggregation-induced emission molecule carries a certain positive charge, the surface of the bacteria has electronegativity, and the electropositive aggregation-induced emission molecule is easy to aggregate on the surface of the bacteria due to the electrostatic interaction between the positive charge and the negative charge, so that a precondition is provided for the selective imaging of gram-positive bacteria; because the cell membrane of the bacteria is composed of phospholipid bilayers, the appropriate lipid-water partition coefficient (3< ClogP <5) enables the aggregation-induced emission molecule to be inserted into the cell membrane of the bacteria, and limits the movement of the aggregation-induced emission molecule, thereby emitting fluorescence; because the envelope structures of gram-positive bacteria and gram-negative bacteria are different, the deep red/near infrared multifunctional aggregation-induced emission material disclosed by the invention is easier to insert into the cell membrane of the gram-positive bacteria when being co-cultured with the bacteria, so that the specific 'lighting' imaging of the gram-positive bacteria is realized; the aggregation-induced emission molecule has a strong electron donating (D) -electron withdrawing (A) effect, which results in red shift of absorption and emission wavelength of the molecule, and has deep red/near infrared fluorescence emission and strong ROS generation capability.
The deep red/near infrared multifunctional aggregation-induced emission material is co-cultured with gram-positive bacteria and gram-negative bacteria for a certain time respectively, then the fluorescence intensity is observed or detected under a microscope, and whether the gram-positive bacteria exist or not can be judged according to the existence of a fluorescence signal.
The deep red/near infrared multifunctional aggregation-induced emission material can detect a strong fluorescent signal after being combined with gram-positive bacteria, but the gram-negative bacteria can not detect the fluorescent signal of the compound. At the same time, the compound has high Reactive Oxygen Species (ROS) generating capacity, and even at low concentration (1 mu M), the fluorescence intensity of the ROS indicator reaches more than 1000 times of the initial value.
Further, the deep red/near infrared multifunctional aggregation-induced emission material can efficiently kill gram-positive bacteria through photodynamic.
The above-mentioned properties of the aggregation-inducing luminescent material are further explained below by means of specific examples.
Specific imaging of gram-positive bacteria
(1) Bacterial culture and bacterial imaging fluid preparation
Transferring single bacterial colony on the solid agar plate to 10mL of corresponding liquid culture medium, and culturing for 6-8 hours at 37 ℃ and 200rpm (culture medium: LB for escherichia coli and pseudomonas aeruginosa, NB for staphylococcus aureus and TSB for staphylococcus aureus)Enterococcus faecalis). After centrifugation (7100rpm, 2 minutes), the upper layer of the culture was discarded, and the lower layer was washed twice with PBS. After removal of the supernatant, the remaining bacteria were resuspended in PBS and diluted to an optical density of 1.0 (OD) at 600nm6001.0, about 108CFU mL-1)。
(2) Bacterial staining and imaging
Through the above procedure, 500. mu.L of bacteria (OD) was obtained600After centrifugation (7100rpm, 2 minutes) again, the supernatant was removed, 50. mu.L of PBS solution (2 μm) was added to the remaining bacteria, vortexed and incubated for 20 minutes. About 2. mu.L of the stained bacterial solution was transferred onto a glass slide, and then covered with a cover slip for imaging. Coli and S.aureus were imaged under a fluorescent Microscope (Upper Biological Microscope Ni-U) with the following settings: an excitation filter is 460-490nm, a dichroic mirror is 505nm, and an emission filter is 515nm long-pass; pseudomonas aeruginosa and enterococcus faecalis were imaged using a confocal fluorescence microscope (FV1200-IX83, Olympus, Japan) with an excitation wavelength of 488nm and fluorescence signals were collected in the range of 530-700 nm.
FIGS. 2a-2d are CLSM plots of TPy, TPPy, TTPy, MeOTTPy (2. mu.M) incubated with E.coli and S.aureus, respectively, for 20 minutes.
FIG. 3 is a CLSM plot of TPy, TPPy, TTPy, MeOTTPy (2. mu.M) incubated with P.aeruginosa and E.faecalis, respectively, for 20 minutes. As can be seen from the figure, after being incubated with TPy, TPPy, TTPy and MeOTTPy (2 μ M), the gram-positive staphylococcus aureus and enterococcus faecalis all emitted bright fluorescence with higher signal-to-noise ratio; gram-negative E.coli and P.aeruginosa emit little fluorescence. The above results indicate that TPy, TPPy, TTPy, MeOTTPy can selectively image gram-positive bacteria.
Photodynamic killing of gram-positive bacteria
(1) Detection of reactive oxygen species in solution
White light detection (22.1mW cm) using 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) as an ROS indicator-2) IrradiationLower aggregation induces ROS production of luminescent molecules in solution.
First, DCFH-DA in ethanol (1mM, 0.5mL) was added to 2mL NaOH solution (0.01M) and stirred at room temperature for 30 minutes to hydrolyze DCFH-DA to DCFH, which was then neutralized with 10mL 1 XPBS at pH 7.4 to give an activated ROS indicator (40. mu.M, 12.5mL), which was stored at 4 ℃ in the dark until needed.
Then, the activated ROS indicator (40 μ M) and aggregation-inducing luminescent molecule were mixed in PBS to give final concentrations of ROS indicator and aggregation-inducing luminescent molecule of 10 μ M/5 μ M and 50nM/1 μ M, respectively, and after white light irradiation for various periods of time, the fluorescence intensity of 2', 7' -dichlorofluorescein triggered by ROS production by aggregation-inducing luminescent molecule was measured by fluorescence spectrometer (Edinburgh FS5) to reflect ROS production. The excitation wavelength is 488nm, and the fluorescence signal in the range of 490-600nm is collected.
FIG. 4a shows the white light (22.1mW cm)-2) The irradiation time is prolonged, and the fluorescence intensity of the mixed solution of TPy, TPPy, TTPy, MeOTTPy (50nM) and ROS indicator DCFH (10 mu M) is enhanced by multiple; 4b is white light (22.1mW cm)-2) The irradiation time was extended and the fluorescence intensity of the mixture of TTPy (1. mu.M) and ROS indicator DCFH (5. mu.M) was increased by a factor of two. As can be seen from FIG. 4a, the DCFH alone is almost non-fluorescent, and after TPy, TPPy, TTPy and MeOTTPy are added, the DCFH fluorescence is gradually enhanced along with the extension of the white light irradiation time, thus proving that TPy, TPPy, TTPy and MeOTTPy can effectively generate ROS under the white light irradiation. As shown in FIG. 4b, when TTPy concentration is 1 μ M, DCFH exhibits an increase in fluorescence intensity of 1000 times the initial value after 30s of white light irradiation, indicating a high ROS-generating ability.
(2) Photodynamic killing of gram-positive bacteria
The antibacterial activity of aggregation-induced emission molecules against escherichia coli and staphylococcus aureus was evaluated by conventional plate culture and colony counting methods.
For the examination of the antibacterial activity of aggregation-induced emission molecules in the dark, the aggregation-induced emission molecules (2. mu.M) were compared with E.coli/Staphylococcus aureus (. about.2X 10)7CFU mL-1) Co-incubation of the PBS suspension for 20 min (3)At 7 ℃ C. Next, the incubated bacterial suspension was serially diluted 10 with PBS4And (4) doubling. 100 μ L of the diluted bacteria were spread on corresponding solid agar plates and incubated at 37 ℃ for 14-16 hours. The antibacterial activity of the aggregation-inducing luminescent molecule against bacteria was evaluated based on the reduced colony ratio. Bacterial colonies on agar plates were counted and analyzed according to the equation [ (A-B)/A)]X 100% calculation of the proportion of colony number reduction, where A is the average number of bacterial colonies (no aggregation-inducing luminescent molecule) in the control sample and B is the average bacterial colony number after incubation with aggregation-inducing luminescent molecule and/or light treatment. The results were repeated three times.
With respect to the antibacterial activity of aggregation-inducing luminescent molecules under light, bacteria were incubated with aggregation-inducing luminescent molecules for 5 minutes in the dark and then in white light (60mW cm)-2) Irradiation was continued for 15 minutes. The rest of the experimental work was the same as in the dark.
FIGS. 5a and 5b show the presence/absence of TTPy (2. mu.M) and/or white light (60 mWcm) of Escherichia coli and Staphylococcus aureus, respectively-2) Photographs of agar plates under conditioned conditions and corresponding statistical plots of colony counts. As can be seen from the figure, the TTPy-free treated group showed good growth of E.coli and S.aureus on agar plates in dark and light conditions; the single TTPy treatment has no obvious antibacterial effect on escherichia coli and staphylococcus aureus; the TTPy and the illumination jointly process the group, almost no staphylococcus aureus visible colony grows on the agar plate, the colony number reduction proportion is close to 100 percent, and the escherichia coli colony number on the agar plate has no obvious change, which shows that the TTPy can specifically kill the gram-positive bacteria through the photodynamic action. FIG. 5(C) shows Staphylococcus aureus in the presence/absence of TTPy (2. mu.M) and/or white light (60mW cm)-2) Scanning electron microscopy images under conditioned conditions. As can be seen, the integrity of the Staphylococcus aureus envelope is destroyed by the combined action of TTPy and light, resulting in the death of gram-positive bacteria.
In vivo antibacterial and anti-infection
16 common male Wistar rats of 6-8 weeks were randomly divided into 4 groups: (1) by TTPy
And a white light illuminated treated bacterial infected group; (2) aloneInfection of the group with TTPy-treated bacteria; (3) untreated bacterial-infected group; (4) control group without bacterial infection. After anesthetizing the rats, the skin on both sides of the dorsal spine was removed, and two 1.5X 1.5 cm/rat were prepared2The rat was inoculated with 50. mu.L of a Staphylococcus aureus suspension (2X 10)8CFU mL-1) And establishing a wound model of staphylococcus aureus infection. For the TTPy treatment group, 50 μ L TTPy (4 μ M) was added to each wound and covered with sterile non-woven for 20 minutes. Subsequently, white light (60mW cm)-2) The wound was irradiated for 30 minutes or not. The operations of TTPy injection and white light irradiation were performed once a day for 4 days. The wound area was imaged with a camera on day 1 and 4 post infection. All mice were collected on day 4 post-infection with whole wounds and adjacent normal skin. To determine the amount of bacteria in the infected tissue of rats, the infected tissue was isolated and homogenized in physiological saline, and then diluted 1000-fold with physiological saline. 20 μ L of the diluted bacterial solution was spread on an LB agar plate and cultured at 37 ℃. After 24 hours, bacterial colonies on the plates were counted and analyzed. Other tissues were fixed in 4% paraformaldehyde, and paraffin sections with a thickness of 4mm were prepared for histological analysis.
FIG. 6a first and second rows of S.aureus infected rat wounds with/without TTPy (2. mu.M) and/or white light (60mW cm)-2) Photographs of the wound on the first and fourth days after conditioning; the third and fourth rows are HE staining and partial magnification of wound tissue sections on day four, respectively. As can be seen in the figure, all staphylococcus aureus infected groups exhibited a degree of wound suppuration the first day after infection; on the fourth day, the wound suppuration of the staphylococcus aureus infected group without any treatment and TTPy alone treatment is aggravated, and the wound suppuration of the rats of the staphylococcus aureus infected group treated with TTPy and white light irradiation is obviously relieved; at the same time, H&The staining result of E shows that the neutrophil count of the TTPy and white light co-treated group is obviously reduced compared with other groups, which indicates that the TTPy can kill staphylococcus aureus in vivo through photodynamic and effectively control wound infection.
FIGS. 6b and 6c are the colony maps of the agar plates coated with the homogeneous suspension of the wound tissue corresponding to the photograph in FIG. 6a for 14-16 h, and the statistical plots of the corresponding colony counts. As can be seen from the figure, almost no Staphylococcus aureus colony was formed on the agar plates corresponding to the control group and the TTPy and white light co-treatment group, and more bacterial colonies were formed on the agar plates corresponding to the bacterial infection group treated with the single light and the TTPy, further indicating that the TTPy can kill Staphylococcus aureus in vivo by photodynamic.
In conclusion, the invention provides a deep red/near infrared multifunctional aggregation-induced emission material, and a preparation method and application thereof. The molecular structure of the aggregation-induced emission material provided by the invention has a pyridine ring carrying a certain positive charge, which is beneficial to the combination of the aggregation-induced emission material and bacteria through electrostatic interaction. Due to the difference of the envelope structures of gram-positive bacteria and gram-negative bacteria, the molecule can realize specific 'lighting' imaging of the gram-positive bacteria when being co-cultured with the bacteria; the strong electron-donating (D) -electron-withdrawing (A) effect of the molecule itself causes the red shift of the absorption and emission wavelength of the molecule, and has deep red/near infrared fluorescence emission and strong ROS generation capacity.
Meanwhile, the deep red/near infrared multifunctional aggregation-induced emission material provided by the invention can efficiently kill gram-positive bacteria.
It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.
Claims (10)
1. A deep red/near infrared multifunctional aggregation-induced emission material is characterized by being selected from any one of molecular structural formulas (I) to (IV):
wherein R is1、R2Each independently selected from H,
One of (1);
X-independently selected from I-、PF6 -、BF4 -、SbF6 -、SbF5 -、CH3COO-、CF3COO-、CO3 2-、SO4 2-、SO3 2-、CF3SO2 -、TsO-、ClO4 -、F-、Cl-、Br-、(F3CSO2)N-、PO4 3-One kind of (1).
2. A method for preparing the deep red/near infrared multifunctional aggregation-inducing luminescent material with the molecular structural formula (I) as claimed in claim 1, wherein the method comprises the steps of:
step 11, adding 4- (diphenylamino) benzaldehyde and 1, 4-dimethylpyridine-1-iodide into a reaction vessel, adding absolute ethyl alcohol under the protection of nitrogen, adding piperidine as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring a reaction solution into absolute ethyl ether to obtain orange solid powder;
step 12, dissolving the orange solid powder in acetone, mixing the solution with saturated potassium hexafluorophosphate aqueous solution, stirring the mixture for 0.5 to 2 hours at the temperature of 25 ℃, and filtering the mixture to obtain an orange solid TPy;
the molecular structural formula of TPy is
3. The method for preparing a deep red/near infrared multifunctional aggregation-induced emission material according to claim 2, wherein the first reaction condition is a temperature of 70-85 ℃.
4. A method for preparing the deep red/near infrared multifunctional aggregation-inducing luminescent material with molecular structural formula (II) as claimed in claim 1, wherein the method comprises the steps of:
step 21, adding 4-bromotriphenylamine, 4-formylphenylboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate into a reaction vessel, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating after the reaction to obtain a first intermediate product;
step 22, mixing the first intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under a first reaction condition, standing overnight, and pouring the reaction solution into absolute ethyl ether to obtain first red solid powder;
step 23, dissolving the first red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain a first red solid TPPy;
the molecular structural formula of the TPPy is shown in the specification
5. The method for preparing a deep red/near infrared multifunctional aggregation-induced emission material as claimed in claim 4, wherein the second reaction condition is a reflux reaction at a temperature of 60-80 ℃.
6. The method for preparing a deep red/near infrared multifunctional aggregation-induced emission material as claimed in claim 4, wherein the second reaction condition is a reflux reaction at a temperature of 60-80 ℃ for 15-18 hours.
7. A method for preparing a deep red/near infrared multifunctional aggregation-inducing luminescent material with molecular structural formula (III) as claimed in claim 1, which comprises the steps of:
step 31, mixing 4-bromotriphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a second intermediate product after the reaction;
step 32, mixing the second intermediate product and 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine serving as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into the anhydrous ether to obtain second red solid powder;
step 33, dissolving the second red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain second red solid TTPy;
the molecular structural formula of the TTPy is shown in the specification
8. A method for preparing a deep red/near infrared multifunctional aggregation-inducing luminescent material of molecular structural formula (IV) according to claim 1, comprising the steps of:
step 41, mixing 4-bromo-4 ',4' -dimethoxy triphenylamine, 5-aldehyde-2-thiopheneboronic acid, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride and potassium carbonate, adding a mixed solvent of toluene and methanol under the protection of nitrogen, reacting under a second reaction condition, and separating to obtain a third intermediate product after the reaction;
step 42, mixing the third intermediate product with 1, 4-dimethylpyridine-1-iodide, adding absolute ethyl alcohol under the protection of nitrogen, dropwise adding piperidine as a catalyst, carrying out reflux reaction under the first reaction condition, standing overnight, pouring the reaction liquid into anhydrous ether, and pouring the reaction liquid into anhydrous ether to obtain third red solid powder;
step 43, dissolving the third red solid powder in acetone, mixing with saturated potassium hexafluorophosphate aqueous solution, stirring for 0.5-2 hours at 25 ℃, and filtering to obtain a third red solid MeOTTPy;
the molecular structural formula of the MeOTTPy is shown as
9. The method for preparing a deep red/near infrared multifunctional aggregation-induced emission material according to any one of claims 4 to 7, wherein the volume ratio of toluene to methanol in the mixed solvent of toluene and methanol is 1: 1.
10. Use of the deep red/near infrared multifunctional aggregation-inducing luminescent material according to claim 1 for gram-positive bacteria specific labeling or for gram-positive bacteria photodynamic killing.
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