Heliotropin-modified ruthenium polypyridine complex as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of antibacterial medicines, and particularly relates to a heliotropin-modified ruthenium polypyridine complex as well as a preparation method and application thereof. The structural formula of the ruthenium polypyridine complex is shown as a formula I. According to the polypyridine ruthenium complex modified by the heliotropin structure, the bacterial cell membrane penetrating capacity and the retention effect of the polypyridine ruthenium complex are enhanced. As the ruthenium complex has a rigid octahedral geometric structure, the structure is easier to modify, so that the ruthenium complex can more easily optimize the binding affinity of cell targets compared with organic drugs; the polypyridine structure is a typical nitrogen-containing heterocyclic compound, so that the polypyridine structure has more target spots, and can be used for breaking bacterial cell membranes, thereby inhibiting the generation of bacterial toxins; and the formula I of the # imgabs0 # is shown in the specification.

Description

Technical Field

[0001] This application belongs to the technical field of antibacterial medicine, and specifically relates to a ruthenium polypyridine complex modified with piperonal, its preparation method and application. Background Art

[0002] Staphylococcus aureus α-toxin is a key virulence factor secreted by Staphylococcus aureus and plays a key role in various Staphylococcus aureus infections. Therefore, inhibiting α-toxin can effectively reduce bacterial pathogenicity.

[0003] In recent years, with the widespread use of antibiotics, the problem of drug resistance in Staphylococcus aureus has become increasingly serious. In particular, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) has brought great challenges to clinical treatment.

[0004] There is a close and complex relationship between hemolysis and bacterial infection. Bacterial infection can trigger hemolysis, and the occurrence of hemolysis will in turn affect the process of bacterial infection and the development of the disease. After red blood cells rupture and hemolyze, substances such as hemoglobin and iron released can provide nutrients for the growth and reproduction of bacteria. Hemolysis can also affect the body's immune response and exacerbate inflammation, etc. Similarly, the active toxins produced by bacteria can directly damage red blood cells and destroy the living environment of blood cells by causing acidosis and hypoxia in the body.

[0005] Therefore, developing drugs that can inhibit bacterial growth and the hemolysis problem caused by bacterial toxins is an urgent problem to be solved. Summary of the Invention

[0006] The purpose of the present invention is to solve the deficiencies of the prior art and provide a ruthenium polypyridine complex modified with piperonal, its preparation method and application. The specific technical solutions are as follows: In the first aspect, the present invention provides a ruthenium polypyridine complex modified with piperonal, and the structural formula of the ruthenium polypyridine complex is shown as Formula I: Formula I; Wherein, is selected from the following structures: .

[0007] The ruthenium polypyridine complex modified with piperonal provided by the present invention contains ruthenium ions and carries a positive charge, while the bacterial cell membrane usually carries a negative charge. Positively charged organic molecules can interact with the phospholipid bilayer of the bacterial cell membrane through electrostatic interaction, resulting in the destruction of the cell membrane, leakage of intracellular substances, and the inability of the bacteria to produce toxins, thereby inhibiting bacterial growth. At the same time, the ruthenium complex has a multi-coordination configuration, which can enable it to be modified with different ligands, thereby making its biological activity higher.

[0008] In a second aspect, the present invention provides a method for preparing the above-mentioned ruthenium polypyridyl complex modified with piperonal, comprising the following steps: Dissolve the compound shown in formula a and the compound shown in formula b in a solvent, and carry out a coordination substitution reaction under the condition of a protective gas to obtain the ruthenium polypyridyl complex modified with piperonal; The structure of the compound shown in formula a is as follows: ; The structure of the compound shown in formula b is as follows: ; wherein, is selected from the following structures: .

[0009] In the above preparation method, the present invention uses a ruthenium complex as an auxiliary ligand. Ruthenium belongs to transition metals, and ruthenium complexes have good biocompatibility, electrochemical and photophysical properties, and can form small molecule compounds and nanomaterials. In addition, ruthenium polypyridyl complexes usually carry a positive charge, while the surface of bacterial cell membranes usually carries a negative charge. This charge complementarity enables the complex to bind to the surface of the bacterial membrane through electrostatic interaction, thereby destroying the integrity of the membrane. The molecular structure of ruthenium polypyridyl complexes has hydrophobicity or specific functional groups, and these characteristics enable them to insert into the lipid bilayer of the bacterial membrane. This insertion may cause a change in the membrane fluidity, destroy the barrier function of the membrane, and thus increase the membrane permeability. Therefore, the present invention can achieve the destruction of bacterial membranes by modifying ruthenium polypyridyl complexes, thereby inhibiting the production of bacterial toxins.

[0010] As a further preferred embodiment, the compound shown in formula a is prepared by the following process: Mix 1,10-phenanthroline-5,6-dione, 6-nitro-piperonal and ammonium acetate, and under acid catalysis, carry out a keto-aldehyde condensation reaction between the carbonyl group provided by 1,10-phenanthroline-5,6-dione and the aldehyde group provided by 6-nitro-piperonal to obtain the compound shown in formula a.

[0011] In the above preparation process, the present invention mixes 1,10-phenanthroline-5,6-dione, 6-nitropiperonal and ammonium acetate. Under acid catalysis, the carbonyl group provided by 1,10-phenanthroline-5,6-dione reacts with the aldehyde group provided by 6-nitropiperonal to undergo a keto-aldehyde condensation reaction, forming a main ligand containing piperonal. During the reaction, ammonium acetate will dissociate to a certain extent to generate ammonium ions and undergo a nucleophilic addition reaction with 6-nitropiperonal, and an imine product is formed through a dehydration reaction. At the same time, the nitrogen atom of the imine will attack the carbonyl carbon of 1,10-phenanthroline-5,6-dione, forming a new negatively charged oxygen intermediate. The negatively charged oxygen intermediate can react with another carbonyl group of 1,10-phenanthroline-5,6-dione through an intramolecular electron transfer and proton transfer process, forming a new carbon-oxygen bond. At the same time, a double bond is formed between the nitrogen atom and another carbonyl carbon, and an intramolecular cyclization reaction occurs to generate a product containing a heterocyclic structure, obtaining a main ligand containing piperonal (the compound shown in formula a).

[0012] As a further preferred embodiment, the molar ratio of 1,10-phenanthroline-5,6-dione, 6-nitropiperonal and ammonium acetate is 1:1:29 - 31.

[0013] As a further preferred embodiment, the temperature of the keto-aldehyde condensation reaction is 120°C - 140°C, and the time is 2h - 4h.

[0014] As a further preferred embodiment, the molar ratio of the compound shown in formula a and the compound shown in formula b is 1:0.9 - 1.1.

[0015] As a further preferred embodiment, the temperature of the coordination substitution reaction is 140°C - 160°C, and the time is 6h - 10h; the solvent includes ethylene glycol.

[0016] In the third aspect, the present invention provides the application of the above-mentioned ruthenium polypyridine complex modified with piperonal in the preparation of antibacterial drugs.

[0017] As a further preferred embodiment, the preparation of antibacterial drugs includes drugs for inhibiting bacteria.

[0018] As a further preferred embodiment, the bacteria include Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

[0019] The beneficial effects of the present invention are: (1) The present invention provides a polypyridyl ruthenium complex with a piperonal structure modification. Ruthenium polypyridyl complexes usually carry a positive charge, while the surface of bacterial cell membranes usually carries a negative charge. This charge complementarity enables the complex to bind to the surface of the bacterial membrane through electrostatic interaction, thereby destroying the integrity of the membrane and inhibiting bacterial growth. At the same time, compared with traditional organic small molecules, the polypyridyl ruthenium complex modified with a piperonal structure in the present invention enhances its ability to penetrate bacterial cell membranes and the retention effect. Due to the rigid octahedral geometric structure of the ruthenium complex, it is easier to modify the structure, so it can optimize the binding affinity of cell targets more easily than organic drugs. The polypyridyl structure is a typical nitrogen-containing heterocyclic compound, which enables it to have more targets, achieve the destruction of bacterial cell membranes, and thus inhibit the production of bacterial toxins.

[0020] (2) The present invention uses 1,10-phenanthroline-5,6-dione and 6-nitropiperonal to carry out a keto-aldehyde condensation reaction to form a main ligand containing piperonal. Then, the main ligand containing the piperonal small molecule is introduced into the auxiliary ligand containing ruthenium element to synthesize polypyridyl ruthenium complexes with three different auxiliary ligands. The polypyridyl ruthenium complex with a piperonal structure in the present invention can effectively inhibit Staphylococcus aureus, quickly kill Staphylococcus aureus, and can inhibit the release of hemolysin toxin by Staphylococcus aureus, weakening its pathogenicity. Therefore, the polypyridyl ruthenium complex with a piperonal structure provided by the present invention has certain potential in inhibiting hemolysis. Brief Description of the Drawings

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1 The nuclear magnetic resonance hydrogen spectrum of Ru-1 is shown.

[0023] Figure 2 The HPLC (high performance liquid chromatography) of Ru-1 is shown.

[0024] Figure 3 The nuclear magnetic resonance hydrogen spectrum of Ru-2 is shown.

[0025] Figure 4 The HPLC of Ru-2 is shown.

[0026] Figure 5 The nuclear magnetic resonance hydrogen spectrum of Ru-3 is shown.

[0027] Figure 6 The HPLC of Ru-3 is shown.

[0028] Figure 7 Shown are the plate coating diagrams of the bacterial suspension after Ru-3 at different concentrations acts on Staphylococcus aureus for different times.

[0029] Figure 8 Shown is the hemolysis rate of the Ru-3 complex on Staphylococcus aureus at different concentrations. Detailed implementation manners

[0030] Next, the technical solutions in the embodiments of the present application will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are some, but not all, of the embodiments of the present application. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application without making creative efforts shall fall within the protection scope of the present application.

[0031] The present invention provides a preparation method of a piperonal-modified ruthenium polypyridine complex, and its preparation route is as shown below: ; Among them, formula b is selected from any one of the following structures: .

[0032] The chemical formulas of the above formula b-1, b-2, and b-3 are Ru(bpy)2Cl2·2H2O, Ru(dmb)2Cl2·2H2O, and Ru(dtb)2Cl2·2H2O respectively; bpy represents 2,2′-bipyridine, dmb represents 4,4′-dimethyl-2,2′-bipyridine, and dtb represents 4,4′-di-tert-butyl-2,2′-bipyridine.

[0033] Example 1 A preparation method of a piperonal-modified ruthenium polypyridine complex specifically includes the following steps: (1) Prepare the main ligand, and its preparation reaction route is as shown below: The specific preparation process is as follows: Weigh 210.0 mg of 1,10-phenanthroline-5,6-dione, 195.0 mg of 6-nitropiperonal and 2312.4 mg of ammonium acetate into a 250 mL reaction flask, then add 60 ml of acetic acid, and reflux and stir at 130 °C for 3 h; after the reaction solution is cooled, add water for dilution, and adjust the pH to neutral with ammonia water to precipitate a yellow solid; the precipitate after vacuum filtration is recrystallized with ethanol as the solvent to obtain a pure product, and then dried under vacuum to obtain 2-(6-nitrobenzo[d][1,3]dioxoleno[5,4-f][1,10]phenanthroline as shown in formula a, that is, the main ligand (formula a), with a yield of 70%; (2) Preparation of piperonal-modified polypyridyl ruthenium complex (Ru-1), and its preparation reaction route is as follows: The specific preparation process is as follows: Add 115.52 mg of the main ligand as shown in formula a and 158.7 mg of Ru(bpy)2Cl2·2H2O into a 50 mL three-necked flask, and dissolve them in ethylene glycol; under the protection of argon, stir and reflux at 150 °C for 8 h, after the reaction is completed, cool to room temperature, and then add a saturated potassium hexafluorophosphate solution to precipitate a large amount of red-brown solid; filter and collect the precipitate, and dry it under vacuum to obtain a crude product; the crude product is separated and purified by a neutral alumina column with a mixed solution of xylene and acetonitrile as the concentration gradient eluent; among them, the volume ratio of xylene to acetonitrile is 2:1 to obtain the piperonal-modified polypyridyl ruthenium complex (Ru-1).

[0034] The above-prepared product Ru-1 was characterized by 1H NMR, and the results are as Figure 1 shown: 1 1H NMR (600 MHz, DMSO) δ 8.87 (d, J J = 8.3 Hz, 2H), 8.84 - 8.79 (m, 4H), 8.19 (t, J J = 7.9 Hz, 2H), 8.08 (t, J J = 7.9 Hz, 2H), 7.87 (d, J J = 5.6 Hz, 2H), 7.76 (d, J J = 5.2 Hz, 2H), 7.71 - 7.68 (m, 2H), 7.57 (q, J J = 5.8 Hz, 5H), 7.44 (s, 1H), 7.35 (t, J J = 6.7 Hz, 2H), 6.22 (s, 2H).

[0035] The purity of the prepared product Ru-1 was verified by HPLC, and the results are as Figure 2 shown, and the purity of Ru-1 was 99.65%.

[0036] Example 2 A preparation method of a piperonal-modified ruthenium polypyridyl complex specifically includes the following steps: (1) Prepare the main ligand, and the preparation process is the same as that in step (1) of Example 1.

[0037] (2) Prepare the piperonal-modified ruthenium polypyridyl complex (Ru-2), and its preparation reaction route is as follows: The specific preparation process is as follows: Add 115.52 mg of the main ligand shown in formula a and 162.1 mg of Ru(dmb)2Cl2·2H2O into a 50 mL three-necked flask, and dissolve them in ethylene glycol; under the protection of argon, stir and reflux at 150 °C for 8 h. After the reaction is completed, cool to room temperature, add a saturated potassium hexafluorophosphate solution, and a large amount of red-brown solid will precipitate; filter and collect the precipitate, and obtain the crude product after vacuum drying; the crude product is separated and purified by a neutral alumina column using a mixed solution of xylene and acetonitrile as the concentration gradient eluent; among them, the volume ratio of xylene to acetonitrile is 3:1 to obtain the piperonal-modified ruthenium polypyridyl complex (Ru-2).

[0038] The prepared product Ru-2 was characterized by 1H NMR, and the results are as Figure 2 shown: 1 1H NMR (600 MHz, DMSO) δ 8.78 (d, J J = 8.3 Hz, 2H), 8.73 (s, 2H), 8.68 (s, 2H), 7.77 (d, J J = 5.3Hz, 2H), 7.69 (d, J J = 6.4 Hz, 4H), 7.59 (s, 1H), 7.45 (s, 1H), 7.40 (d, J J = 6.0Hz, 2H), 7.36 (d, J J = 5.9 Hz, 2H), 7.16 (d, J J = 6.0 Hz, 2H), 6.23 (s, 2H), 2.55(s, 6H), 2.43 (s, 6H).

[0039] The purity of the prepared product Ru-2 was verified by HPLC, and the results are as Figure 4 shown, and the purity of Ru-1 was 95.76%.

[0040] Example 3 A preparation method of a piperonal-modified ruthenium polypyridine complex, specifically including the following steps: (1) Prepare the main ligand, and its preparation process is the same as that of step (1) in Example 1.

[0041] (2) Prepare the piperonal-modified polypyridine ruthenium complex (Ru-3), and its preparation reaction route is as follows: The specific preparation process is as follows: Add 115.52 mg of the main ligand shown in formula a and 212.6 mg of Ru(dtb)2Cl2·2H2O into a 50 mL three-necked flask, and dissolve them in ethylene glycol; under the protection of argon, stir and reflux at 150 °C for 8 h. After the reaction is completed, cool to room temperature, add a saturated potassium hexafluorophosphate solution, and a large amount of red-brown solid will precipitate; filter and collect the precipitate, and obtain the crude product after vacuum drying; the crude product is separated and purified by a neutral alumina column using a mixed solution of xylene and acetonitrile as the concentration gradient eluent; among them, the volume ratio of xylene to acetonitrile is 5:1, and the piperonal-modified polypyridine ruthenium complex (Ru-3) is obtained.

[0042] Perform 1H NMR characterization on the above-prepared product Ru-3, and the results are as Figure 3 shown: 1 1H NMR (600 MHz, DMSO) δ 8.87 (s, 2H), 8.83 (s, 2H), 8.80 (d, J = 7.9 Hz, 2H), 7.75 - 7.68 (m, 6H), 7.60 (d, J = 6.0 Hz, 2H), 7.58 (s, 1H), 7.47 - 7.42 (m, 3H), 7.36 (d, J = 6.3 Hz, 2H), 6.23 (s, 2H), 1.42 (s, 18H), 1.32 (s, 18H).

[0043] Verify the purity of the above-prepared product Ru-3 by HPLC, and the results are as Figure 6 shown, and the purity of Ru-1 is 98.45%.

[0044] Example 4 Perform antibacterial experiment tests on the above-prepared piperonal-modified ruthenium polypyridine complex (1) Determine the MIC values of Ru-1, Ru-2 and Ru-3, and the specific method is as follows: Culture the Staphylococcus aureus strain (Escherichia coli strain / Pseudomonas aeruginosa strain) in TSB medium until the logarithmic growth phase; dilute it 1000 times with fresh medium to obtain a bacterial suspension. Add 50 µL of metal ruthenium complexes and ligands with different concentrations into the 96-well plate in sequence, and then add 200 µL of the bacterial suspension to each well, so that the final concentration of each well is 200 µg / mL, 100 µg / mL, 50 µg / mL, 25 µg / mL, 12.5 µg / mL, 6.25 µg / mL, 3.125 µg / mL, 1.56 µg / mL, 0.78 µg / mL, 0.39 µg / mL from left to right. Add 50 µL of sterile water to the last well as a blank control, and measure 3 parallel groups for each drug. After incubating at 37 °C for 20 h, monitor the growth of bacteria by observing the turbidity of the culture, and the lowest drug concentration corresponding to the clear drug well is the MIC (minimum inhibitory concentration).

[0045] The results are shown in Table 1. For Staphylococcus aureus, the MIC values of Ru-1, Ru-2, and Ru-3 are 200 µg / mL, 12.5 µg / mL, and 0.78 µg / mL, respectively.

[0046] For Escherichia coli, the MIC values of Ru-1, Ru-2, and Ru-3 are 100 µg / mL, 100 µg / mL, and 100 µg / mL, respectively.

[0047] For Pseudomonas aeruginosa, the MIC values of Ru-1, Ru-2, and Ru-3 are 50 µg / mL, 50 µg / mL, and 50 µg / mL, respectively.

[0048] Table 1 MIC values of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa corresponding to Ru-1, Ru-2, and Ru-3 (2)Time-kill kinetic experiment: Ru-3 at concentrations of 1 × MIC, 2 × MIC, 4 × MIC, and 8 × MIC were separately mixed with the Staphylococcus aureus culture solution. The suspension was placed in a shaker at 37°C and shaken at 220 r / min for 10 h. Then, 1 mL of the suspension was first aspirated using a pipette and centrifuged at a high speed of 5000 rpm for 2 min to obtain the bacterial supernatant. 2 mL of defibrinated rabbit blood was placed in a centrifuge tube and centrifuged at a high speed of 2000 rpm for 2 min. The supernatant was discarded, and the rabbit red blood cells were preserved. 150 μL of the bacterial supernatant and 25 μL of the rabbit red blood cells were added to 1 mL of PBS buffer and incubated in an environment at 37°C for 30 min to obtain three sample solutions. PBS and the culture medium were set as blank control groups; PBS buffer was added to the rabbit red blood cells and washed repeatedly three times as the PBS blank control group, denoted as PBS; a positive experimental group with only bacteria and rabbit red blood cells added was set, denoted as Ctrl; three samples were taken for experiments in each group.

[0049] The results are as Figure 7 shown, Figure 7 in which are the time-killing effect diagrams of Ru-3 complexes on Staphylococcus aureus at different concentrations; from left to right, they are 0 min, 30 min, 60 min, 90 min, and 120 min; from top to bottom, they are 1 × MIC, 2 × MIC, 4 × MIC, and 8 × MIC. The results show that as the concentration increases, the effect of Ru-3 becomes more and more obvious. When the concentration is 8 × MIC and the time is 1.5 h, there are no colonies growing on the culture dish, that is, at this time Ru-3 can kill all bacteria, indicating that Ru-3 has excellent bactericidal effects and can quickly kill bacteria in a short time.

[0050] (3) Experiment on inhibiting the secretion of bacterial hemolysin: Ru-3 at concentrations of 0.2 μg / mL, 0.39 μg / mL, and 0.59 μg / mL were separately mixed with the Staphylococcus aureus culture solution. The suspension was placed in a shaker at 37 °C and shaken at 220 r / min for 10 h. Then, 1 mL of the suspension was first aspirated using a pipette and centrifuged at a high speed of 5000 rpm for 2 min to obtain the bacterial supernatant. 2 mL of defibrinated rabbit blood was placed in a centrifuge tube and centrifuged at a high speed of 2000 rpm for 2 min. The supernatant was discarded, and the rabbit red blood cells were preserved. 150 μL of the bacterial supernatant and 25 μL of the rabbit red blood cells were added to 1 mL of PBS buffer and incubated in an environment at 37 °C for 30 min to obtain three sample solutions. PBS and the culture medium were set as blank control groups; PBS buffer was added to the rabbit red blood cells and washed repeatedly three times as the PBS blank control group, denoted as PBS; a positive experimental group with only bacteria and rabbit red blood cells added was set, denoted as Ctrl; three samples were taken for each group for the experiment.

[0051] The results are as Figure 8 shown, Figure 8 in which are the hemolysis rates of the Ru-3 complexes at different concentrations. Through the hemolysis test, it shows that the clearer the color of the supernatant, the stronger the inhibitory effect on bacterial toxins. The incubated suspension was centrifuged at a high speed of 2000 rpm for 2 min, and the supernatant was taken to measure the absorbance at 543 nm to quantitatively determine the rupture of red blood cells and calculate the hemolysis rate. The hemolysis rates of 0.2 μg / mL, 0.39 μg / mL, and 0.59 μg / mL were quantitatively detected by OD543 nm absorbance. The secretion of hemolytic toxins of the Ru-3 complexes at the concentrations of 0.2 μg / mL, 0.39 μg / mL, and 0.59 μg / mL decreased by 16.01%, 47.19%, and 94.94% respectively. This indicates that the piperonal-modified polypyridyl ruthenium complex prepared in the present invention can significantly reduce the secretion of Staphylococcus aureus hemolytic toxins.

[0052] The embodiments of the present application have been described above in conjunction with the accompanying drawings. Specific examples have been used herein to elaborate on the principles and implementation manners of the present application. The description of the above embodiments is only for helping to understand the core idea of the present application. However, the present application is not limited to the above specific implementation manners. The above specific implementation manners are only illustrative and not restrictive. Those of ordinary skill in the art, under the inspiration of the present application, without departing from the purpose of the present application and the scope protected by the claims, can also make many forms, all of which fall within the protection scope of the present application.

Claims

1. A piperonal-modified ruthenium polypyridine complex, characterized in that: The structural formula of the ruthenium polypyridine complex is shown in Formula I: Formula I; in, Selected from the following structures: 。 2. The method for preparing the piperonal-modified ruthenium polypyridine complex according to claim 1, characterized in that: The following steps are involved: The compound represented by formula a and the compound represented by formula b are dissolved in a solvent, and a coordination substitution reaction is carried out under protective gas conditions to obtain the piperonal-modified ruthenium polypyridine complex; The structure of the compound represented by formula a is shown below: ； The structure of the compound represented by formula b is as follows: ;in, Selected from the following structures: 。 3. The preparation method according to claim 2, characterized in that: The compound represented by formula a is prepared by the following process: 1,10-phenanthroline-5,6-dione, 6-nitropiperonal and ammonium acetate are mixed, and under acid catalysis, a ketoaldehyde condensation reaction is carried out between the carbonyl group provided by 1,10-phenanthroline-5,6-dione and the aldehyde group provided by 6-nitropiperonal to obtain the compound represented by formula a.

4. The preparation method according to claim 3, characterized in that: The molar ratio of the 1,10-phenanthroline-5,6-dione, 6-nitropiperonal and ammonium acetate is 1:1:29-31.

5. The preparation method according to claim 3, characterized in that: The temperature of the ketoaldehyde condensation reaction is 120° C. to 140° C., and the time is 2 h to 4 h.

6. The preparation method according to claim 2, characterized in that: The molar ratio of the compound represented by formula a to the compound represented by formula b is 1:0.9-1.

1.

7. The preparation method according to claim 2, characterized in that: The temperature of the coordination substitution reaction is 140° C. to 160° C., and the time is 6 h to 10 h; and the solvent includes ethylene glycol.

8. Use of the piperonal-modified ruthenium polypyridine complex according to claim 1 in the preparation of antibacterial drugs.

9. The use according to claim 8, characterized in that: The antibacterial drugs prepared include drugs that inhibit bacteria.

10. The use according to claim 8, characterized in that: The bacteria include Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

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