A monosubstituted formic acid hydroxyaluminum phthalocyanine, its preparation method and application

Abstract

This invention discloses a monosubstituted formate hydroxyaluminum phthalocyanine, its preparation method, and its applications, the structural formula of which is shown below. The monosubstituted formate hydroxyaluminum phthalocyanine of this invention can be used to prepare photosensitizers, photodynamic drugs, or photosensitizing drugs. The compound of this invention has the following characteristics: it exists in water as a monomer, has a strong ability to generate reactive oxygen species, low dark toxicity, and high phototoxicity. Its phototherapy index (PI) is greater than 223713, far exceeding that of approved phthalocyanine photosensitizing drugs (PI = 725).

Description

Technical Field

[0001] This invention belongs to the field of photosensitizers, specifically relating to a monosubstituted formic acid hydroxyaluminum phthalocyanine, its preparation method, and its application. Background Technology

[0002] Phthalocyanine compounds were initially used as dyes, but as research into phthalocyanines progressed, their diverse applications were discovered. They can be used to synthesize electrode materials, solar cell materials, photocatalytic materials, electrocatalytic materials, contrast agents in photothermal therapy, and photodynamic therapy, among others.

[0003] Over the past few decades, photodynamic therapy (PDT) has become a widely used treatment for various precancerous lesions and malignant tumors. PDT involves injecting a photosensitizer into the body. After a period of time, the photosensitizer accumulates at the target site. The target is then irradiated with light of a specific wavelength (for targets within body cavities, the light source can be introduced using interventional techniques such as fiber optics). The photosensitizer accumulated in the target, under photoexcitation, triggers a series of photophysical and photochemical reactions, generating reactive oxygen species, which in turn destroy the target (e.g., cancer cells and cancerous tissue). Due to its non-invasive or minimally invasive nature, this method has many potential applications.

[0004] PDTs do not exhibit cumulative toxicity, and their activation can be controlled spatially and temporally. The tunable light used and the short diffusion radius of reactive oxygen species (ROS) minimize damage to surrounding healthy tissues. Phthalocyanine photosensitizers have attracted widespread attention due to their maximum absorption wavelength in the red light region, facilitating easy propagation through human tissues. However, currently reported biologically active phthalocyanine complexes still have some drawbacks, such as poor stability, complex synthetic routes, poor bioselectivity, and easy aggregation in aqueous solutions. Summary of the Invention

[0005] Objective of the Invention: To address the problems existing in the prior art, this invention provides a monosubstituted formate hydroxyaluminum phthalocyanine, which exhibits high phototoxicity and low dark toxicity; after irradiation with low-dose light at 680 nm, the drug's dark toxicity IC50 is [not specified in the original text]. 50 With phototoxic IC 50 The phototoxicity index (PI) exceeds 223713, indicating that it has good safety. This phthalocyanine exists in water in monomer form, which is beneficial for exerting photodynamic activity in water. It is expected to be used as a photosensitizer for photodynamic therapy of cancer.

[0006] This invention also provides a method for preparing and applying the monosubstituted formate hydroxyaluminum phthalocyanine.

[0007] Technical solution: To achieve the above objectives, the present invention provides a monosubstituted formate hydroxyaluminum phthalocyanine, the structural formula of which is as follows:

[0008]

[0009] The preparation method of the monosubstituted carboxylic acid hydroxyaluminum phthalocyanine photosensitizer of the present invention includes the following steps:

[0010] (1) Using 4-nitrophthalonitrile with ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate and pentyl p-hydroxybenzoate as reactants, respectively, the corresponding compounds (ethyl 4-(3,4-dicyanophenoxy)benzoate), (methyl 4-(3,4-dicyanophenoxy)benzoate) and (pentyl 4-(3,4-dicyanophenoxy)benzoate) were generated.

[0011] (2) Ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate are cyclized with phthalonitrile to generate compounds 2 and 3, respectively.

[0012] (3) The mixture of compound 2 and compound 3 was separated to obtain compound 2;

[0013] (4) Compound 2 is hydrolyzed and deesterified to obtain monosubstituted carboxylic acid hydroxyaluminum phthalocyanine, compound 4;

[0014] The reaction formula for using ethyl p-hydroxybenzoate and (4-(3,4-dicyanophenoxy)ethyl benzoate) is shown below:

[0015]

[0016] In the reaction process, DMF refers to N,N-dimethylformamide, n-pentanol refers to n-pentanol, and DBU refers to 1,8-diazacyclo[5,4,0]undecene-7.

[0017] In step (1), 4-nitrophthalonitrile and ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate are used as reactants, and N,N-dimethylformamide is used as solvent. The mixture is stirred at 60-80°C for 24-48 hours in the presence of potassium carbonate and under nitrogen protection. After the reactants have reacted completely, the target product compound 1 is precipitated in water.

[0018] In step (1), the molar ratio of 4-nitrophthalonitrile to ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate, or pentyl p-hydroxybenzoate is 1:1-1.1, the amount of solvent used is 2-4 mL per mole of 4-nitrophthalonitrile, and the amount of potassium carbonate used is 0.93-1.1 mol per mole of 4-nitrophthalonitrile.

[0019] In step (2), ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate and phthalonitrile are used as raw materials, n-pentanol is used as solvent, aluminum chloride is added, and 1,8-diazacyclo[5,4,0]undecene-7 is used as catalyst. Under nitrogen protection, the reaction is carried out at 130-140℃ for 10-12 hours to obtain compound 2 and compound 3.

[0020] In step (2), the molar ratio of ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate, phthalonitrile, and aluminum chloride is 1:9-12:3.5-5; the amount of catalyst used is 2-3 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate; and the amount of solvent used is 20-40 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate.

[0021] In step (3), the target product compound 2 is obtained by column chromatography purification.

[0022] In step (4), compound 2 is used as the raw material, an alkaline reagent is added, and the reaction is carried out at 80-100℃ for 10-12 hours to obtain the target product.

[0023] In step (4), a 5-20% sodium hydroxide aqueous solution is used, and the amount used is 0.3-0.5 mL per milligram of compound 2.

[0024] As a preferred method, the preparation steps of the monosubstituted formate hydroxyaluminum phthalocyanine photosensitizer are as follows:

[0025] Step (1): The molar ratio of 4-nitrophthalonitrile to ethyl p-hydroxybenzoate is 1:1. The amount of solvent used is 2-4 mL per mole of 4-nitrophthalonitrile, and the amount of potassium carbonate used is 0.93 mol per mole of 4-nitrophthalonitrile. Under nitrogen protection, the mixture is stirred at 75°C for 30 hours. After the reaction is complete, the target product is precipitated in water.

[0026] Step (2): The molar ratio of ethyl 4-(3,4-dicyanophenoxy)benzoate, phthalonitrile, and aluminum chloride is 1:11:3.5-4; the amount of catalyst DBU is 2-3 mL per mol of ethyl 4-(3,4-dicyanophenoxy)benzoate; the amount of solvent n-pentanol is 20-30 mL per mol of ethyl 4-(3,4-dicyanophenoxy)benzoate. The reaction is carried out at 140℃ for 12 hours under nitrogen protection. During the reaction, the ethyl ester in the cyclized ethyl 4-(3,4-dicyanophenoxy)benzoate undergoes an transesterification reaction with the solvent n-pentanol, converting the ethyl ester to the pentyl ester. After the reaction was completed, the reaction solution was cooled to room temperature, and n-pentanol was removed by vacuum distillation. The resulting blue-black solid was refluxed at 70°C for 2-3 hours with methanol (30 mL) and concentrated hydrochloric acid (2 mL). The filter cake was collected by hot filtration and washed with methanol (15 mL each time, 3 times). The resulting solid was placed in a vacuum drying oven to dry, and a blue solid (a mixture of compound 2 and compound 3) was obtained.

[0027] Step (3): Dissolve the solid in dichloromethane, dry and mix the sample, and perform crude purification by column chromatography. Use dichloromethane / methanol / acetic acid = 200:4:1-200:5:1 (v / v / v) as the eluent to obtain monosubstituted pentyl formate chloroaluminophthalocyanine as a blue solid.

[0028] Step (4): Weigh compound 2 and add 10% sodium hydroxide aqueous solution. The amount of 10% sodium hydroxide aqueous solution is 0.3-0.5 mL per milligram of compound 2. Reflux at 100℃ for 12 h. Cool the reaction solution to room temperature and add concentrated hydrochloric acid to adjust the pH to 7-8. Stir at room temperature for 30 min and add deionized water (30 mL). A large amount of blue solid precipitates. Centrifuge to collect the precipitate and wash it three times with distilled water (25-30 mL each time). Place the obtained solid in a vacuum drying oven to dry and obtain compound 4 as a blue solid.

[0029] The application of the monosubstituted formic acid hydroxyaluminum phthalocyanine described in this invention in the preparation of photosensitizers, photodynamic drugs, or photosensitizing drugs.

[0030] The monosubstituted carboxylic acid hydroxyaluminum phthalocyanine described in this invention has excellent photosensitizing activity and good physiological compatibility, making it suitable as a photosensitizer for photodynamic therapy of tumors.

[0031] This invention presents for the first time a method for synthesizing and isolating monosubstituted aluminum formate phthalocyanine, which exhibits a significantly superior phototherapy index (PI) far exceeding that of conventional photosensitizers. The monosubstituted aluminum formate phthalocyanine prepared in this invention belongs to the category of photosensitizers, photodynamic drugs, or photosensitizing agents. The compounds described in this invention have the following characteristics: they exist in water as monomers, exhibit strong reactive oxygen species generation capacity, low dark toxicity, and high phototoxicity. The phototherapy index (PI) is greater than 223713, significantly higher than that of approved phthalocyanine photosensitizers. (CAS122170-90-5)(PI=725).

[0032] In the preparation and synthesis of monosubstituted aluminum formate phthalocyanine, if the carboxyl group of the phthalocyanine precursor is not protected and the reaction is carried out directly, the reaction will not succeed. Similarly, if the amount of catalyst DBU is not reached as specified in this invention, the reaction will also fail. Furthermore, without the addition of acetic acid during the separation process, compound 2 is difficult to separate. This invention is the first to synthesize monosubstituted aluminum formate phthalocyanine. The synthesis products of monosubstituted aluminum formate phthalocyanine include monosubstituted pentyl formate chloroaluminophthalocyanine (compound 2) and unsubstituted aluminum phthalocyanine (compound 3). The properties of unsubstituted aluminum phthalocyanine are very similar to those of monosubstituted aluminum formate chloroaluminophthalocyanine, making the separation of the target product (compound 2) difficult. In contrast, the tetrasubstituted aluminum formate phthalocyanine synthesis product consists only of the product itself, making separation easy. Moreover, compared to tetrasubstituted aluminum phthalocyanine... Its phototoxicity activity is 2.07 μM, which is 2315 times lower than that of monosubstituted hydroxyaluminum phthalocyanine, and significantly lower than that of the monosubstituted phthalocyanine of this invention.

[0033] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0034] This invention represents the first synthesis of monosubstituted formate hydroxyaluminum phthalocyanine. Experiments on in vitro cancer cells using the monosubstituted formate hydroxyaluminum phthalocyanine prepared by this invention show that this type of complex exhibits low dark toxicity but high phototoxicity. After irradiation with low-dose light at 680 nm, the drug's dark toxicity IC50 is [not specified in the original text]. 50 With phototoxic IC 50 The phototoxicity index (PI) exceeds 223,713, far higher than that of approved phthalocyanine photosensitizing drugs. (PI = 725). This compound exhibits strong absorption within the phototherapy window (600-900 nm); under photosensitizing conditions, it can effectively generate various reactive oxygen species. It exists in water in monomeric form, which is beneficial for its photodynamic activity in aquatic bodies, and it holds promise as a photosensitizer for photodynamic therapy of cancer. Attached Figure Description

[0035] Figure 1 For monosubstituted formate hydroxyaluminum phthalocyanine (10) -5 mol / L) and monosubstituted amyl formate chloroaluminophthalocyanine (10 -5 UV-Vis absorption spectrum of (mol / L) in aqueous phase;

[0036] Figure 2 For monosubstituted formate hydroxyaluminum phthalocyanine (10) -5 The ability of mol / L to generate singlet oxygen in an aqueous phase;

[0037] Figure 3 Dark toxicity of monosubstituted formate hydroxyaluminum phthalocyanine in human bladder cancer cells T24;

[0038] Figure 4 Phototoxicity of monosubstituted formate hydroxyaluminum phthalocyanine in human bladder cancer cells T24. Detailed Implementation

[0039] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0040] Unless otherwise specified, the experimental methods described in the embodiments are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0041] Example 1

[0042] Synthesis of monosubstituted formate hydroxyaluminum phthalocyanine

[0043]

[0044] The specific steps are as follows:

[0045] (1) Ethyl 4-(3,4-dicyanophenoxy)benzoate: 4-nitrophthalonitrile (2.598 g, 15.0 mmol), ethyl p-hydroxybenzoate (2.49 g, 15.0 mmol), potassium carbonate (2.0 g, 14.0 mmol) and DMF (30 mL) were added sequentially to the reaction flask. The mixture was stirred at 75 °C for 30 h under N2 protection. After the reaction was completed, the reaction solution was poured into ice water at ten times the volume of the solvent and stirred for 30 minutes. A large amount of white solid precipitated out. The solid was filtered and the filter cake was washed three times with water. The filter cake was then dried in an oven at 50 °C for 12 h to obtain compound 1 (ethyl 4-(3,4-dicyanophenoxy)benzoate). 1H NMR (400MHz, CDCl3) δ8.17 (d, J=8.5Hz, 2H), 7.79 (d, J=8.7Hz, 1H), 7.36 (s, 1H), 7.31 (d, J=8.7Hz, 1H), 7.14 (d, J=8.5Hz, 2H), 4.43 (q, J=7.1Hz, 2H), 1.43 (t, J=7.1Hz, 3H).

[0046] (2) Monosubstituted pentyl formate chloroaluminophthalocyanine: Under nitrogen protection, ethyl 4-(3,4-dicyanophenoxy)benzoate (386 mg, 1.32 mmol), phthalonitrile (1.87 g, 14.59 mmol), aluminum chloride (707 mg, 5.3 mmol), and n-pentanol (40 mL) were added to a three-necked flask, refluxed and heated to 95 °C, activated for 0.5 h, DBU (3 mL) was added, and the temperature was rapidly increased to 140 °C. The reflux was maintained under these conditions for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, and n-pentanol was removed by vacuum distillation. The resulting blue-black solid, a mixture of compounds 2 and 3, was refluxed at 70°C for 2 hours with methanol (30 mL) and concentrated hydrochloric acid (2 mL, 37% by mass). The mixture was filtered while hot, and the filter cake was collected. The filter cake was washed with methanol (15 mL each time, 3 times). The resulting solid was dried in a vacuum drying oven to obtain a blue solid (1.5 g, a mixture of monosubstituted pentyl formate chloroaluminophthalocyanine and unsubstituted chloroaluminophthalocyanine). The solid was dissolved in 25 mL of dichloromethane, dried, and mixed. The sample was purified by column chromatography using dichloromethane / methanol / acetic acid = 200:4:1 (v / v / v) as the eluent to obtain monosubstituted pentyl formate chloroaluminophthalocyanine as a blue solid (compound 2) (80 mg, yield: 7.75%). 1 H NMR (400MHz, DMSO) δ9.80-9.58 (m, 6H), 9.24 (d, J = 2.0Hz, 1H), 8.68-8.36 (m, 7H), 8.29-8.16 (m, 3H), 7.64-7. 52(m,2H),4.38-4.31(m,2H),1.83-1.74(m,2H),1.27(dd,J=18.1,9.1Hz,4H),0.93(dd,J=11.9,4.7Hz,3H).

[0047] (3) Monosubstituted formate hydroxyaluminum phthalocyanine: Take 60 mg of monosubstituted formate chloroaluminum phthalocyanine, add 30 mL of 10% sodium hydroxide aqueous solution, and reflux at 100 °C for 12 h. Cool the reaction solution to room temperature, add concentrated 37% hydrochloric acid to adjust the pH to 7.5, stir at room temperature for 30 min, add deionized water (30 mL), and a large amount of blue solid precipitates. Centrifuge to collect the precipitate, wash with distilled water (25 mL each time, three times), and place the obtained solid in a vacuum drying oven to dry, and obtain monosubstituted formate hydroxyaluminum phthalocyanine as a blue solid (compound 4) (47 mg, yield: 88.35%). 1H NMR(400MHz, DMSO)δ9.78-9.58(m,7H),9.22(d,J=2.1Hz,1H),8.59-8.39(m,6H),8.28-8.16(m,3H),7.60-7.51(m,2H).HRMS(ESI,+ve)calcd.for C 39 H 21 AlN8O4 + : 692.630, Found [M+H] + : 693.157.

[0048] Example 2

[0049] The steps (2) and (3) are basically the same as those in Example 1, but in step (1) of Example 1, ethyl p-hydroxybenzoate is changed to methyl p-hydroxybenzoate, and the resulting monosubstituted formate hydroxyaluminum phthalocyanine has the same structure.

[0050] Example 3

[0051] The steps (2) and (3) are basically the same as those in Example 1, but in step (1) of Example 1, ethyl p-hydroxybenzoate is changed to pentyl p-hydroxybenzoate, and the resulting monosubstituted formate hydroxyaluminum phthalocyanine has the same structure.

[0052] Example 4

[0053] The steps (1), (2), and (3) of Example 1 are basically the same, except that 4-nitrophthalonitrile in step (1) is replaced with an equimolar amount of 3-nitrophthalonitrile, and the resulting phthalocyanine substituent is at the α-position.

[0054]

[0055] The monosubstituted hydroxyaluminum phthalocyanine synthesized in Example 1 has a side chain at the β position. According to Example 4, monosubstituted hydroxyaluminum phthalocyanine at the α position can be synthesized. Different side chain positions may lead to different properties, different reactive oxygen generation capabilities, and may also change the activity, providing more product variations.

[0056] Example 5

[0057] The absorption spectra and states of matter in water of compounds 4 and 2 prepared in Example 1 were compared. Figure 1 In an aqueous system, 10 μM monosubstituted aluminum formate phthalocyanine exhibited the spectral characteristics of a monomer, showing a strong monomer absorption band near 690 nm, significantly stronger than the aggregate absorption band at 630 nm, indicating that it exists primarily in water as a monomer. Monosubstituted pentyl formate aluminum phthalocyanine showed a distinct broad peak at 630 nm, indicating that it exists as an aggregate. Figure 1The absorption peak of monosubstituted aluminum formate at 690 nm is higher than that at 630 nm, indicating that it is predominantly a monomer in water. The monosubstituted aluminum formate chlorophthalocyanine shows a broad peak at 630 nm, indicating it is an aggregate. This demonstrates that monosubstituted aluminum formate is predominantly a monomer in water and does not readily aggregate; the aggregated state affects its activity.

[0058] Example 6

[0059] like Figure 2 Example 1: Preparation of the singlet oxygen generation capacity of monosubstituted formate hydroxyaluminum phthalocyanine and monosubstituted formate pentyl chloride phthalocyanine in aqueous phase. 3 μL of a 10... -2 mol / L of monosubstituted formic acid hydroxyaluminum phthalocyanine and 30 μL of 10 - 2 Add mol / L ADPA (singlet oxygen probe, anthracene-9,10-dipropionic acid CAS: 71367-28-7) to a cuvette containing 3 mL of distilled water, and measure at 680 nm (25 mW / cm²). 2 Irradiation with red light was performed, and the ultraviolet absorption spectrum was measured every 5 minutes. The same experimental procedure was followed for monosubstituted pentyl formate aluminum phthalocyanine. The results showed that monosubstituted hydroxyaluminum formate aluminum phthalocyanine had a significantly higher singlet oxygen generation capacity than monosubstituted pentyl formate aluminum phthalocyanine, likely due to their different aggregation states in the aqueous phase. Monosubstituted hydroxyaluminum formate aluminum phthalocyanine is predominantly monomeric in the aqueous phase, resulting in a stronger singlet oxygen generation capacity.

[0060] like Figure 2 The rate of change of the UV absorption peak of ADPA was significantly stronger for monosubstituted formate hydroxyaluminum phthalocyanine than formate pentyl formate aluminum phthalocyanine.

[0061] Example 7

[0062] The method for preparing a photodynamic drug (i.e., a photosensitizing agent) using the monosubstituted formate hydroxyaluminum phthalocyanine prepared in Example 1 of this invention is as follows: Using dimethyl sulfoxide as a solvent, the phthalocyanine metal complex described in this invention is dissolved to prepare a uniform blue solution (i.e., a photosensitizing agent) with a concentration of 10... -2 The concentration of the phthalocyanine metal complex in the photosensitizer should not exceed its saturation concentration (mol / L). Antioxidants, buffers, and isotonic agents can be added to the prepared solution as additives to maintain the chemical stability of the photosensitizer.

[0063] Example 8

[0064] 1 mM of the monosubstituted formate hydroxyaluminum phthalocyanine prepared in Example 1 was diluted in serum-free DMEM culture medium to prepare DMEM solutions containing phthalocyanine complexes at different concentrations. Bladder cancer (T24) cells were cultured at 10... 5Cells were inoculated at a density of 100 μL / well in 96-well plates and cultured in 5% CO2 at 37°C in the dark for 24 hours. Different concentrations of DMEM containing phthalocyanine were then added, and the cells were cultured in the dark for another 12 hours. The light-illuminated experimental group was then subjected to 680 nm (25 mW / cm²) microplate chromatography. 2 The cells were irradiated with red light for 10 minutes; no light irradiation was required for the non-illuminated group. Cell viability was detected using the CCK8 assay.

[0065] like Figure 3 The dark toxicity activity of monosubstituted hydroxyaluminum phthalocyanine against bladder cancer cells (T24). Figure 4 The phototoxic activity of monosubstituted hydroxyaluminum phthalocyanine against bladder cancer cells (T24) was investigated. Results showed that without light exposure, the IC50 concentration was significantly reduced. 50 At concentrations greater than 200 μM, monosubstituted formate hydroxyaluminum phthalocyanine showed no killing or growth-inhibiting effect on human bladder cancer cells T24, indicating no dark toxicity; however, under red light irradiation, monosubstituted formate hydroxyaluminum phthalocyanine exhibited significant photodynamic activity, with an IC50 concentration of [missing value]. 50 The value is 0.894 nM. The PI value is greater than 223713, which is much higher than that of approved phthalocyanine photosensitizing drugs. (PI=725).

[0066]

[0067] The phthalocyanine photosensitizers reported in the literature (ACS Med. Chem. Lett. 2021, 12, 502-507) The phototoxicity is 2.07 μM, and the dark toxicity is greater than 1500 μM. High-PI photosensitizers exhibit low cytotoxicity in the dark, thus having less impact on normal tissues and cells under non-light conditions, thereby reducing side effects during treatment and improving treatment safety. High-PI photosensitizers also demonstrate stronger selective killing of cancer cells when selectively irradiating tumor tissue.

Claims

1. A monosubstituted hydroxyaluminum carboxy phthalocyanine characterized in that, The monosubstituted carboxylic acid hydroxy aluminum phthalocyanine has the following structure: 。 2. A process for the preparation of monosubstituted hydroxyaluminum carboxylic phthalocyanine according to claim 1, characterized in that, The method comprises the following steps: (1) 4-nitrophthalonitrile is used as a reactant with ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate, and N,N dimethylformamide is used as a solvent, and the reaction is carried out under the presence of potassium carbonate and nitrogen protection, and stirring is carried out at 60-80°C for 24-48 hours, and the corresponding compound is obtained by precipitation in water after the reactants are completely reacted. (2) Ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate is used as a raw material with phthalonitrile, n-pentanol is used as a solvent, aluminum chloride is added, 1,8-diazocyclo [5,4,0] undecene-7 is used as a catalyst, and the reaction is carried out under nitrogen protection at 130-140°C for 10-12 hours to obtain compound 2 and compound 3. (3) The mixture of compound 2 and compound 3 is separated to obtain compound 2. (4) Compound 2 is subjected to hydrolysis and deesterification to obtain monosubstituted carboxylic acid hydroxy aluminum phthalocyanine, compound 4. The reaction formula of ethyl p-hydroxybenzoate and ethyl 4-(3,4-dicyanophenoxy)benzoate is shown in the following formula: 。 3. The method for preparing monosubstituted formate hydroxyaluminum phthalocyanine according to claim 2, characterized in that, In step (1), 4-nitrophthalonitrile and ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate are used as reactants, N,N dimethylformamide is used as a solvent, and the reaction is carried out under the presence of potassium carbonate and nitrogen protection, and stirring is carried out at 60-80°C for 24-48 hours, and the corresponding compound is obtained by precipitation in water after the reactants are completely reacted.

4. The method of preparing monosubstituted aluminum hydroxyphthalocyanine according to claim 3, wherein the monosubstituted aluminum hydroxyphthalocyanine is represented by the following formula (1) : ###0001### (1) wherein R represents a hydrogen atom or a hydrocarbon group. In step (1), the molar ratio of 4-nitrophthalonitrile and ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate is 1:1-1.1, the solvent dosage is 2-4 mL per mole of 4-nitrophthalonitrile, and the potassium carbonate dosage is 0.93-1.1 mol per mole of 4-nitrophthalonitrile.

5. The method of preparing monosubstituted aluminum hydroxyphthalocyanine according to claim 2, wherein the monosubstituted aluminum hydroxyphthalocyanine is represented by the following formula (2) : ###0002### (2) wherein R represents a hydrogen atom or a methyl group. In step (2), ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate and phthalonitrile are used as raw materials, n-pentanol is used as a solvent, aluminum chloride is added, 1,8-diazocyclo [5,4,0] undecene-7 is used as a catalyst, and the reaction is carried out under nitrogen protection at 130-140°C for 10-12 hours to obtain compound 2 and compound 3.

6. The method of preparing monosubstituted aluminum hydroxyphthalocyanine according to claim 5, wherein the monosubstituted aluminum hydroxyphthalocyanine is represented by the following formula (1) : ###0001### (1) wherein R represents a hydrogen atom or a hydrocarbon group. In step (2), the molar ratio of ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate and phthalonitrile and aluminum chloride is 1:9-12:3.5-5, the catalyst dosage is 2-3 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate, and the solvent dosage is 20-40 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate.

7. The method for preparing monosubstituted formate hydroxyaluminum phthalocyanine according to claim 2, characterized in that, In step (3), the target product compound 2 is obtained by column chromatography purification.

8. The method for preparing monosubstituted formic acid hydroxyaluminum phthalocyanine according to claim 2, characterized in that, In step (4), compound 2 is used as a raw material, an alkaline reagent is added, and the reaction is carried out under reflux at 80-100°C for 10-12 hours to obtain the target product.

9. The method for preparing monosubstituted formic acid hydroxyaluminum phthalocyanine according to claim 8, characterized in that, The amount of the 5-20% sodium hydroxide aqueous solution used in step (4) is 0.3-0.5 mL per mg of compound 2.

10. Use of the monosubstituted aluminum hydroxyphthalocyanine of claim 1 in the preparation of a photosensitizer or a photodynamic drug or a photosensitive drug.

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