A photosensitizer based on porphyrin and triphenylamine pyridine salt, preparation method and application thereof

Abstract

This invention discloses a photosensitizer based on porphyrin and triphenylamine pyridine salt, its preparation method, and its application, belonging to the field of photosensitizer technology. Addressing the medical and health problems caused by bacterial infections and the issues of poor water solubility, easy ACQ formation, and decreased reactive oxygen species (ROS) yield of traditional porphyrin photosensitizers, this photosensitizer uses a copper-coordinated 5,10,15,20-tetra(4-aminophenyl)porphyrin as its core. Substituents containing triphenylamine and eight pyridinium salt cations are introduced through a Schiff base reaction, endowing it with excellent water solubility, high ROS generation efficiency, and bacterial targeting ability. An aldehyde-containing intermediate is obtained through coupling and methylation of the triphenylamine bispyridine unit; a copper porphyrin intermediate is obtained by coordination of the porphyrin with copper acetate; and the two are then condensed through Schiff base to obtain the target product. This photosensitizer has good dispersibility in water and can efficiently generate reactive oxygen species under light. It has excellent photodynamic killing effects on Escherichia coli and methicillin-resistant Staphylococcus aureus, and has good biocompatibility. It can be used to prepare antibacterial photodynamic therapy drugs.

Description

Technical Field

[0001] This invention belongs to the field of photosensitizer technology, specifically relating to a novel and highly efficient photosensitizer based on porphyrin and triphenylamine pyridine salt, and also provides a preparation method and application of the photosensitizer. Background Technology

[0002] Bacterial infections have become a major global public health threat. The overuse and misuse of antibiotics have accelerated the rise of multidrug-resistant (MDR) strains, severely undermining the effectiveness of traditional antimicrobial treatments. Furthermore, their high morbidity and mortality rates continue to place a heavy burden on healthcare resource allocation, socioeconomic development, and human health. According to a systematic analysis published in *The Lancet*, approximately 4.95 million deaths globally in 2019 were related to antimicrobial resistance, with 1.27 million directly attributable to drug-resistant bacterial infections. Extensive clinical and epidemiological evidence further indicates that the morbidity and mortality risk of drug-resistant infections continue to rise. Predictive models show that if current trends continue, drug-resistant infections could cause up to 10 million deaths annually by 2050. More critically, the complex resistance mechanisms exhibited by multidrug-resistant (MDR) bacteria, especially common clinically resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coupled with their biofilm-forming ability, further exacerbate the limitations of traditional antibiotic treatments. To address these increasingly severe challenges, researchers have actively explored various non-antibiotic treatment strategies.

[0003] Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach, offering spatiotemporally controllable, rapid, and highly effective bactericidal effects with a low risk of inducing drug resistance. In aPDT, a photosensitizer is excited to a singlet excited state (S1) under illumination of a specific wavelength of light, and then transitions to a triplet state (T1) via intersystem crossing (ISC). The triplet photosensitizer can then generate reactive oxygen species (ROS) through two different mechanisms: the first mechanism involves electron transfer between the photosensitizer and the biological substrate, generating superoxide anion radicals (·O2). - The second mechanism involves transferring excited-state energy to ground-state molecular oxygen, generating singlet oxygen (·OH) and hydroxyl radicals (·OH). 1 O2). These ROS achieve rapid bacterial killing through multiple synergistic pathways, including oxidizing bacterial cell membrane lipids, disrupting DNA structure, and inactivating key enzymes.

[0004] Among various photosensitizers, porphyrin compounds have become one of the most promising photosensitizers in the field of antibacterial photodynamic therapy (aPDT) due to their excellent chemical modifiability and outstanding photophysical properties. However, traditional porphyrin photosensitizers, due to their large planar conjugated structures, often face problems such as poor water solubility, strong π-π stacking leading to fluorescence quenching (ACQ), and unsatisfactory reactive oxygen species (ROS) generation efficiency, which limit their practical application in the antibacterial field. Therefore, the invention of porphyrin photosensitizers with good water solubility and high ROS generation efficiency is of great significance for solving bacterial infections caused by MDR strains. Summary of the Invention

[0005] In response to the medical and health problems caused by bacterial infections and the problems of poor water solubility, easy occurrence of ACQ and decreased reactive oxygen species yield of traditional porphyrin photosensitizers, this invention provides a photosensitizer based on porphyrin and triphenylamine pyridine salt, which can kill Escherichia coli and MRSA under light conditions.

[0006] This invention employs copper coordination with porphyrin to significantly promote intersystem crossing and extend triplet lifetime through enhanced spin-orbit coupling, thereby greatly improving ROS generation efficiency. Simultaneously, a triphenylamine group with aggregation-induced emission (AIE) properties is introduced into the porphyrin core via a Schiff base reaction. Its propeller-like spatial configuration effectively suppresses close packing between porphyrin molecules, overcoming ACQ defects. Triphenylamine, as a strong electron donor, forms a donor-acceptor (DA) structure with a pyridinium salt acceptor, promoting intramolecular charge transfer and intersystem crossing, further enhancing ROS generation efficiency. Furthermore, the eight pyridinium salts in the PTPyI molecule structure endow it with good water solubility and can selectively bind to negatively charged bacterial cell surfaces through electrostatic interactions, achieving rapid and precise anchoring of bacteria. The negatively charged counterions in the pyridinium salts provide an electron-rich microenvironment for the excited-state photosensitizer, effectively promoting electron transfer and enhancing type I ROS generation.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0008] A photosensitizer based on porphyrin and triphenylamine pyridine salt, said photosensitizer having the structure shown in Formula I:

[0009] The photosensitizer comprises a copper-coordinated porphyrin core, a triphenylamine skeleton, and eight pyridinium salt cationic groups, wherein the triphenylamine skeleton is linked to the porphyrin core via Schiff base bonds.

[0010] A method for preparing small organic molecules based on porphyrin and triphenylamine pyridine salt, comprising the following steps:

[0011] Step 1: Mix 4-(bis(4-bromophenyl)amino)benzaldehyde, potassium carbonate, Pd(PPh3)4, 4-pyridineboronic acid, 1,4-dioxane, and water. Vacuum the mixture under nitrogen and reflux. After the reaction is complete, cool to room temperature, filter, extract, dry the organic phase, remove the solvent by rotary evacuation, and separate by column chromatography to obtain the yellow solid 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde.

[0012]

[0013] Step 2: 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde, iodomethane, and dichloromethane were mixed and reacted at room temperature. After the reaction was complete, the mixture was filtered, washed, and dried under vacuum to obtain a red solid 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridin-1-onium);

[0014]

[0015] Step 3: Under nitrogen protection, 5,10,15,20-tetra-(4-aminophenyl)porphyrin, DMF, methanol, and chloroform were mixed and activated at room temperature. Copper acetate was then added, and the reaction was heated. After the reaction was complete, the mixture was cooled to room temperature, the solvent was removed by rotary evaporation, the pH of the solution was adjusted, and the solution was filtered, washed, and vacuum dried to obtain a purple-black solid, 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II)(CuTPP).

[0016]

[0017] Step 4: 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridin-1-onium), 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) and DMF were mixed, sonicated, and then heated in the dark. After the reaction was complete, the mixture was cooled to room temperature, filtered, washed, and dried under vacuum to obtain a black solid, PTPyI.

[0018]

[0019] Furthermore, in step 1, the molar ratio of 4-(bis(4-bromophenyl)amino)benzaldehyde, 4-pyridineboronic acid, potassium carbonate, and Pd(PPh3)4 is 1:2-8:2-8:0.05-0.4, and the solvent usage is 2 mmol of 4-(bis(4-bromophenyl)amino)benzaldehyde using 4-14 mL of 1,4-dioxane and 0.5-4 mL of water.

[0020] Furthermore, in step 2, the amount of solvent used is 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde and iodomethane in a molar ratio of 1:2 to 10, and the amount of solvent used is 3 mmol of 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde and 5 to 15 mL of dichloromethane.

[0021] Furthermore, in step 3, the molar ratio of 5,10,15,20-tetra(4-aminophenyl)porphyrin to copper acetate is 1:1 to 3, and the solvent usage is as follows: 0.3 mmol of 5,10,15,20-tetra(4-aminophenyl)porphyrin requires 20 to 30 mL of DMF, 10 to 15 mL of methanol, and 60 to 80 mL of chloroform.

[0022] Furthermore, in step 4, the molar ratio of 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) and 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridine-1-onium) is 1:4 to 6, and 0.15 mmol of 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) is obtained using 5 to 15 mL of DMF.

[0023] Furthermore, in step 1, the reflux reaction temperature is 90–120 °C, and the reaction time is 16–24 h; in step 1, the reaction solution is extracted with dichloromethane 2–4 times and dried with anhydrous sodium sulfate.

[0024] Furthermore, in step 2, the reflux reaction temperature is 20–35 °C, and the reaction time is 16–24 h; in step 2, the filter cake is washed with dichloromethane 2–5 times, and the vacuum drying temperature is 50–70 °C, and the drying time is 8–15 h.

[0025] Furthermore, in step 3, the heating temperature is 70–90 °C, and the reaction time is 16–24 h; in step 3, the pH is adjusted to 7–8 with saturated NaHCO3, the vacuum drying temperature is 50–70 °C, and the drying time is 8–15 h.

[0026] Furthermore, in step 4, the temperature for the heating reaction in the dark is 110–130 °C, and the reaction time is 2–4 days; in step 4, the vacuum drying temperature is 50–70 °C, and the drying time is 8–15 h.

[0027] Application of a photosensitizer based on porphyrin and triphenylamine pyridine salt in the treatment of bacterial infections or in antibacterial photodynamic therapy.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] The PTPyI of this invention exhibits good dispersibility and photostability in aqueous solution, stronger bacterial anchoring ability and higher ROS generation efficiency. It can efficiently generate ROS under light conditions and shows excellent photodynamic killing effects on Escherichia coli and MRSA, and has broad application prospects in the field of aPDT. Attached Figure Description

[0030] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0031] Figure 1 This is a particle size distribution diagram of the PTPyI nanoparticles of this invention in water;

[0032] Figure 2 This is a potential diagram of the PTPyI nanoparticles of this invention in water;

[0033] Figure 3 This is the UV-Vis absorption spectrum of CuTPP and PTPyI in DMSO solution and nanoparticles of this invention.

[0034] Figure 4 This is a graph showing the reactive oxygen generation capacity of CuTPP and PTPyI nanoparticles in this invention.

[0035] Figure 5 This is a graph showing the antibacterial properties of the PTPyI nanoparticles of this invention against Escherichia coli at different concentrations.

[0036] Figure 6 This is a graph showing the antibacterial properties of PTPyI nanoparticles against MRSA at different concentrations.

[0037] Figure 7 This is a graph showing the cytotoxicity of the PTPyI nanoparticles of this invention on L929 cells at different concentrations. Detailed Implementation

[0038] To gain a deeper understanding of this invention, we will provide a comprehensive and detailed description. However, this invention has various implementations and is not limited to the specific examples listed herein. These examples are presented to enhance a full understanding of the disclosure of this invention.

[0039] Example 1

[0040] The preparation method of PTPyI includes the following steps:

[0041] Step 1: 4-(bis(4-bromophenyl)amino)benzaldehyde (0.86 g, 2 mmol), potassium carbonate (0.83 g, 6 mmol), Pd(PPh3)4 (0.23 g, 0.2 mmol), 4-pyridineboronic acid (0.74 g, 6 mmol), 10 mL of 1,4-dioxane, and 2 mL of water were added to a 100 mL round-bottom flask. The reaction was carried out at 100 °C for 24 h under nitrogen protection. After the reaction was complete, the mixture was filtered, the solvent was removed by rotary evaporation, 100 mL of dichloromethane was added, and the organic phase was extracted three times with 50 mL of distilled water. The organic phase was dried with anhydrous sodium sulfate and separated by column chromatography (dichloromethane / triethylamine = 100 / 1, v / v) to obtain 0.62 g of a yellow solid 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde, with a yield of 72%. 1 H NMR (600 MHz, CDCl3, ppm) δ: 9.90 (s, 1H), 8.69 (s, 4H), 7.80 (s, 2H), 7.66 (s, 4H), 7.53 (s, 4H), 7.32 (s, 4H), 7.22(s, 2H).

[0042] Step 2: 1.28 g (3 mmol) of 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde and 10 mL of dichloromethane were added to a 50 mL round-bottom flask, followed by 4.98 g (30 mmol) of iodomethane. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the solid was filtered and washed three times with dichloromethane. After vacuum drying, 2.06 g of a red solid, 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridin-1-onium), was obtained, with a yield of 90%. 1 H NMR (400MHz, DMSO-d6, ppm) δ: 9.95 (s, 1H), 8.98 (d, J = 6.8 Hz, 4H), 8.48 (d, J =6.9 Hz, 4H), 8.15 (d, J = 8.7 Hz, 4H), 7.93 (d, J = 8.6 Hz, 2H), 7.36 (d, J =8.7 Hz, 4H), 7.30 (d, J = 8.6 Hz, 2H), 4.33 (s, 6H).

[0043] Step 3: 5,10,15,20-tetratetra-(4-aminophenyl)porphyrin (583 mg, 0.9 mmol) was added to a 250 mL round-bottom flask, followed by 24 mL DMF, 12 mL methanol, and 72 mL chloroform. The mixture was stirred for ten minutes under N2 protection, and then Cu(CH3COO)2 (245 mg, 1.35 mmol) was added. The reaction was stirred at 80 °C for 24 h. After the reaction was complete, the mixture was cooled to room temperature, the solvent was removed by rotary evaporation, 30 mL water and an appropriate amount of NaHCO3 were added, the pH of the solution was adjusted to 8, the mixture was filtered, the filter cake was washed three times with distilled water, and then dried under vacuum at 60 °C for 12 h to obtain 559 mg of the purplish-black solid 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) (CuTPP), with a yield of 84%. 1 H NMR (400 MHz, DMSO-d6, ppm) δ: 8.88 (s, 8H), 7.80 (d, J = 8.0 Hz, 8H), 6.99 (d, J = 8.0 Hz, 8H), 5.52 (s, 8H).

[0044] Step 4: 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridin-1-onium (275 mg, 0.6 mmol) and 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) (110 mg, 0.15 mmol) were added to a 100 mL round-bottom flask, along with 10 mL of DMF and sonicated for 5 minutes. The mixture was reacted at 120 °C in the dark for 3 days. After the reaction was complete, the mixture was cooled to room temperature, filtered, and the filter cake was washed three times with 15 mL of distilled water. The cake was then dried under vacuum at 60 °C for 12 h to obtain 257 mg of black solid PTPyI, with a yield of 48%. 1 H NMR (400 MHz, DMSO-d6, ppm) δ: 9.01-8.89 (m,16H), 8.46 (d, J = 8.2 Hz, 16H), 8.12 (s, 20H), 7.90 (s, 20H), 7.34 (s, 32H),7.22 (s, 4H), 4.31 (d, J = 6.2 Hz, 24H).

[0045] Example 2

[0046] Preparation of PTPyI nanoparticles and measurement of particle size and zeta potential:

[0047] 1) Preparation of nanoparticles:

[0048] PTPyI powder was dissolved in dimethyl sulfoxide (DMSO) to prepare a stock solution with a concentration of 1 mg / mL. Under ultrasonic treatment, 1 mL of this stock solution was added to 1 mL of Pluronic F-127 aqueous solution with a concentration of 5 mg / mL, and ultrasonically mixed for 30 min to obtain a PTPyI nanoparticle stock solution with a concentration of 500 μg / mL. CuTPP nanoparticle stock solutions were prepared using the same procedure.

[0049] 2) Particle size and zeta potential testing of PTPyI nanoparticles:

[0050] The prepared PTPyI nanoparticle stock solution was diluted with ultrapure water to a concentration of 100 μg / mL. Three mL of the 100 μg / mL PTPyI nanoparticle solution was added to a cuvette, and the particle size and potential of both nanoparticles were measured using a Malvern particle size analyzer (Zetasizer Pro). The particle size test results are shown below. Figure 1 The results of the Zeta potential test are shown in [the original text]. Figure 2 .Depend on Figure 1 and Figure 2 It is known that the particle size of PTPyI nanoparticles with a concentration of 100 μg / mL in water is approximately 313 nm, and the Zeta potential is +9.5 mV.

[0051] Example 3

[0052] Ultraviolet absorption spectroscopy of CuTPP and PTPyI nanoparticles

[0053] CuTPP and PTPyI powders were dissolved in DMSO to prepare stock solutions with a concentration of 500 μg / mL. One stock solution was diluted to 20 μg / mL with DMSO to serve as the organic solution test sample. Another stock solution was assembled according to the nanoparticle preparation method and diluted to 20 μg / mL with ultrapure water to serve as the nanoparticle test sample. 3 mL of each sample (DMSO solution and nanoparticle solution, both at a concentration of 20 μg / mL) were placed in cuvettes, and their UV-Vis absorption spectra were measured using a Shanghai Instrument & Electronics Analytical UV-Vis Spectrophotometer (L5S type). The UV-Vis absorption spectral results are shown below. Figure 3 .Depend on Figure 3 It can be seen that the maximum absorption peaks of CuTPP and PTPyI in DMSO are at 597 and 590 nm, respectively, and the maximum absorption peaks of CuTPP and PTPyI nanoparticles in water are at 592 and 593 nm, respectively.

[0054] Example 4

[0055] Test of the ability of CuTPP and PTPyI nanoparticles to generate reactive oxygen species

[0056] Take 50 μL of a 10.0 mM 2,7-dichlorofluorescein diacetate (DCFH-DA) ethanol solution, dilute with 450 μL of ethanol, then add 2.0 mL of 0.01 M NaOH aqueous solution, and activate at room temperature in the dark for 30 min. After activation, add 10 mL of 1×PBS buffer and mix well to obtain a 40 μM 2,7-dichlorodihydrofluorescein (DCFH) working solution. Add 960 μL of the above activated DCFH solution (40 μM) and 40 μL of PTPyI nanoparticles (500 μg / mL) to a cuvette, mix well, and irradiate under a white light source (10 mW / cm²) for 5 min. Use a PerkinElmer fluorescence spectrometer (LS-55) to measure the fluorescence emission intensity of the mixed solution at 525 nm every 1 min at an excitation wavelength of 488 nm. The blank control group consisted of a mixture of 960 μL of activated DCFH solution (40 μM) and 40 μL of ultrapure water, measured under the same light conditions and using the same method. The results are as follows: Figure 4 As shown. By Figure 4 It can be seen that the DCF fluorescence intensity of the PTPyI group rapidly increased within 0–4 min with the extension of illumination time, indicating that PTPyI nanoparticles can efficiently generate reactive oxygen species under illumination. Compared with CuTPP nanoparticles, PTPyI nanoparticles exhibit a faster ROS generation rate under the same conditions.

[0057] Example 5

[0058] Test on the bactericidal effect of PTPyI nanoparticles on Escherichia coli:

[0059] Take the Escherichia coli suspension cultured to the logarithmic growth phase (approximately 10 h), centrifuge at 7100 rpm for 2 min, discard the supernatant, wash the precipitate twice with 10 mM phosphate-buffered saline (PBS, pH=7.4), resuspend, and adjust the bacterial concentration to OD0.05. 600 =1.0. Take 100 μL of this bacterial culture and mix it with different volumes of PTPyI nanoparticles, then add PBS to make up to 500 μL, so that the final concentrations of nanoparticles are 0, 5, 10, and 20 μg / mL, respectively. After incubating the mixture at 37 ℃ in the dark for 20 min, divide it into a light group and a dark group: the light group is incubated at 50 mW / cm 2 The control group was exposed to white light for 15 minutes, while the dark control group was treated under the same conditions in the dark. After incubation, the bacterial cultures of each group were diluted 10 μL with PBS. 4The bacterial suspension was diluted 100 μL and evenly spread onto LB agar plates. The plates were incubated at 37 ℃ for 18 h, and colony counts were performed. Bacterial survival rate (%) was calculated using the formula: (Experimental group colony count / Blank control group colony count) × 100%. The results are as follows: Figure 5 As shown. By Figure 5 It was found that under dark conditions, as the concentration of PTPyI nanoparticles increased, the bacterial survival rate decreased from 100% to 81%, 39%, and 17%, respectively; under light conditions, the bacterial survival rate decreased to 76%, 33%, and 0%, respectively, all exhibiting significant concentration-dependent bactericidal effects. The results indicate that PTPyI nanoparticles possess excellent antibacterial properties against *Escherichia coli*, and the synergistic effect of electrostatic membrane disruption imparted by their high-density pyridinium cations and the generation of reactive oxygen species through photodynamic therapy is key to achieving highly efficient bactericidal activity.

[0060] Example 6

[0061] Test on the bactericidal effect of PTPyI nanoparticles on MRSA:

[0062] Take the MRSA suspension cultured to the logarithmic growth phase (approximately 12 h), centrifuge at 7100 rpm for 2 min, discard the supernatant, wash the precipitate twice with 10 mM phosphate-buffered saline (PBS, pH=7.4), resuspend, and adjust the bacterial concentration to OD0.05. 600 =1.0. Take 100 μL of this bacterial culture and mix it with different volumes of PTPyI nanoparticles. Make up to 500 μL with PBS to achieve final nanoparticle concentrations of 0, 5, 10, 20, and 30 μg / mL. Incubate the mixtures at 37 ℃ in the dark for 20 min, then divide them into light and dark groups: the light group was irradiated with 50 mW / cm² white light for 15 min, while the dark group was treated under the same conditions in the dark. After incubation, dilute each group of bacterial culture with PBS by 10%. 4 Dilute 100 μL of the bacterial suspension and spread it evenly on NB agar plates. Incubate at 37 ℃ for 18 h, then count the colonies. Calculate the bacterial survival rate (%) using the formula: (Experimental group colony count / Blank control group colony count) × 100%. The results are as follows: Figure 6 As shown. By Figure 6 It was found that PTPyI nanoparticles exhibited a significant concentration-dependent bactericidal effect against MRSA. When the concentration of PTPyI nanoparticles was 30 μg / mL, the bacterial survival rate was 52% in the absence of light; however, under light conditions, PTPyI nanoparticles could almost completely kill MRSA (survival rate of only 3%).

[0063] Example 7

[0064] Cytotoxicity test of PTPyI nanoparticles:

[0065] L929 cells in the logarithmic growth phase were seeded into 96-well plates at a density of 1 × 10⁶ cells per well. 4 Cells were incubated at 37 °C for 24 h. Then, the culture medium was replaced with 100.0 μL of fresh medium containing different concentrations of PTPyI nanoparticles (0 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL, 30 μg / mL). After 12 h of incubation, the cells were washed and fresh medium and 10.0 μL of CCK-8 were added. Incubation was continued for another 2 h, and the OD was measured using a microplate reader. 450 .

[0066] Depend on Figure 7 It can be seen that when the concentration of PTPyI nanoparticles is 30 μg / mL, the cell viability is still maintained at over 85%, indicating that it has good biocompatibility.

[0067] Contents not described in detail in this specification are prior art known to those skilled in the art. Although illustrative specific embodiments of the invention have been described above to facilitate understanding by those skilled in the art, it should be understood that the invention is not limited to the scope of the specific embodiments. Various modifications are readily apparent to those skilled in the art as long as they fall within the spirit and scope of the invention as defined and determined by the appended claims, and all inventions utilizing the concept of this invention are protected.

Claims

1. A photosensitizer based on porphyrin and triphenylamine pyridine salt, characterized in that, The photosensitizer has the structure shown in Formula I: The photosensitizer comprises a copper-coordinated porphyrin core, a triphenylamine skeleton, and eight pyridinium salt cationic groups, wherein the triphenylamine skeleton is linked to the porphyrin core via Schiff base bonds.

2. A method for preparing the photosensitizer as described in claim 1, characterized in that, Includes the following steps: (1) 4-(bis(4-bromophenyl)amino)benzaldehyde and 4-pyridineboronic acid were coupled in 1,4-dioxane and water in the presence of tetra(triphenylphosphine)palladium and potassium carbonate to obtain 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde; (2) The product obtained in step (1) is reacted with iodomethane in dichloromethane to give 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridine-1-onium); (3) Under nitrogen protection, 5,10,15,20-tetra-(4-aminophenyl)porphyrin was reacted with copper acetate in a mixed solvent of N,N-dimethylformamide, methanol and chloroform to obtain 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II). (4) The product obtained in step (2) and the product obtained in step (3) are subjected to ultrasonication in N,N-dimethylformamide and then heated in the dark to obtain the photosensitizer PTPyI.

3. The preparation method according to claim 2, characterized in that, The molar ratio of 4-(bis(4-bromophenyl)amino)benzaldehyde, 4-pyridineboronic acid, potassium carbonate and tetra(triphenylphosphine)palladium in step (1) is 1:2-8:2-8:0.05-0.

4.

4. The preparation method according to claim 2, characterized in that, In step (2), the molar ratio of 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzaldehyde to iodomethane is 1:2 to 10; the reaction temperature in step (2) is 20 to 35 °C, and the reaction time is 16 to 24 h.

5. The preparation method according to claim 2, characterized in that, In step (3), the molar ratio of 5,10,15,20-tetra(4-aminophenyl)porphyrin to copper acetate is 1:1 to 3.

6. The preparation method according to claim 2, characterized in that, In step (4), the molar ratio of 5,10,15,20-tetra-(4-aminophenyl)-porphyrin-copper-(II) and 4,4'-(((4-formylphenyl)imino)bis(4,1-biphenyl))bis(1-methylpyridine-1-onium) is 1:4 to 6.

7. The preparation method according to claim 2, characterized in that, The reaction temperature of the coupling reaction in step (1) is 90-120°C and the reaction time is 16-24 hours.

8. The preparation method according to claim 2, characterized in that, In step (3), the heating temperature is 70-90℃ and the reaction time is 16-24 h.

9. The preparation method according to claim 2, characterized in that, In step (4), the temperature for heating and avoiding light is 110-130℃, and the reaction time is 2-4 days.

10. The use of the photosensitizer prepared by the method according to any one of claims 2 to 9 in the preparation of a drug for treating bacterial infections or in the preparation of an antibacterial photodynamic therapy drug.

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