阅读说明：本技术 一种联萘吡啶盐抗菌材料和制备方法及应用 (Dinaphthalene pyridinium antibacterial material and preparation method and application thereof ) 是由 王皓萍 冯丽恒 王美营 于 2020-06-15 设计创作，主要内容包括：本发明涉及小分子抗菌剂技术领域,具体涉及一种联萘吡啶盐抗菌材料和制备方法及应用。S-1,1’-联-2-萘酚与1,4-二(溴甲基)苯反应制备2,2’-双((4-(溴甲基)苄基)氧基)-1,1’-联萘,2,2’-双((4-(溴甲基)苄基)氧基)-1,1’-联萘在DMF中与吡啶反应制备1,1’-((((([[[1,1’-联萘]-2,2’-二基双(氧基))双(亚甲基))双(4,1-亚苯基))双(亚甲基))双(吡啶-1)溴化物。本发明联萘吡啶盐抗菌材料能够有效杀伤革兰氏阴性菌。本发明通过涂布平板法对革兰氏阴性菌的杀伤效果进行确定,在抗菌浓度下对细胞损伤较低,且细胞毒性低。(The invention relates to the technical field of micromolecular antibacterial agents, and particularly relates to a naphthyridine salt antibacterial material, and a preparation method and application thereof. S-1,1 '-bi-2-naphthol reacts with 1, 4-di (bromomethyl) benzene to prepare 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1 '-binaphthyl, and 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1 '-binaphthyl reacts with pyridine in DMF to prepare 1,1' - (((([ [ [1,1 '-binaphthyl ] -2,2' -diylbis (oxy)) bis (4, 1-phenylene)) bis (methylene)) bis (pyridine-1) bromide, the binaphthylpyridinium antibacterial material of the present invention can effectively kill gram-negative bacteria, the present invention is determined by the killing effect of a plate coating method on gram-negative bacteria, has low damage to cells under the antibacterial concentration and low cytotoxicity.)

1. The antibacterial material of the dinaphthyl pyridinium is characterized in that: the structural formula is as follows:

2. a preparation method of a dinaphthyl pyridinium antibacterial material is characterized by comprising the following steps: the method comprises the following steps:

step 1, heating and vigorously stirring S-1,1' -bi-2-naphthol and acetone to obtain a uniform mixed solution, then adding 1, 4-di (bromomethyl) benzene and potassium carbonate into the mixed solution under the protection of inert gas, heating, refluxing and stirring, filtering a solid while the reaction is finished, extracting with dichloromethane and water, collecting an organic phase, drying with anhydrous sodium sulfate, removing the solvent in a vacuum rotary manner, and performing column chromatography on the obtained crude product by using dichloromethane/petroleum ether (1/3 (v/v) as an eluent to obtain 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl;

and 2, adding 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl and pyridine into DMF under the protection of nitrogen, heating to react under stirring, cooling to room temperature, adding into an acetone solution, filtering out a white solid after the white solid is separated out, washing with DMF, acetone and diethyl ether in sequence, and drying in vacuum to obtain 1,1' - ((((([ [ [ [ [1,1' -binaphthyl ] -2,2' -diylbis (oxy)) bis (methylene)) bis (4, 1-phenylene)) bis (methylene)) bis (pyridine-1) bromide, namely the binaphthyl pyridinium antibacterial material.

3. The method for preparing the naphthyridine salt antibacterial material according to claim 2, characterized in that: the mass ratio of the S-1,1' -bi-2-naphthol to the acetone in the step 1 is 1: 18-1: 22;

in the step 1, the molar ratio of 1, 4-bis (bromomethyl) benzene to potassium carbonate is 3.5: 1-5: 1;

the volume ratio of the mixed solution, 1, 4-bis (bromomethyl) benzene and potassium carbonate in the step 1 is 6: 1-8: 1.

4. The method for preparing the naphthyridine salt antibacterial material according to claim 2, characterized in that: the heating time of heating reflux stirring in the step 1 is 6 hours;

the heating temperature for heating and violently stirring in the step 1 is 65 ℃, and the stirring time is 4-8 hours;

the heating temperature of the heating reaction in the step 2 is 70-80 ℃, and the reaction time is 48 h.

5. The method for preparing the naphthyridine salt antibacterial material according to claim 2, characterized in that: the molar ratio of pyridine and 2,2 '-bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl to DMF in step 2 was 2:1: 86.5.

6. The method for preparing the naphthyridine salt antibacterial material according to claim 2, characterized in that: the washing amount of DMF, acetone and diethyl ether is as follows: 150 mL-200 mL;

the temperature of the vacuum drying is 25 ℃, and the time is 48 h.

7. The application of the dinaphthyl pyridinium antibacterial material is characterized in that: can be used for killing gram-negative bacteria.

8. The use of the antibacterial material of a naphthyridine salt according to claim 7, wherein: the gram-negative bacteria include Escherichia coli, Enterobacter cloacae, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

9. An application method of a naphthyridine salt antibacterial material is characterized in that: the killing effect of gram-negative bacteria is determined by a plate coating method, the damage to cells is low under the antibacterial concentration, and the cytotoxicity is low.

Technical Field

The invention relates to the technical field of micromolecular antibacterial agents, and particularly relates to a naphthyridine salt antibacterial material, and a preparation method and application thereof.

Background

Bacteria are widely present in nature and are closely related to human activities. Some bacteria are beneficial bacteria, such as lactic acid bacteria, bifidobacteria, etc. However, some bacteria often cause diseases, such as Salmonella typhimurium which can cause gastrointestinal discomfort and even septicemia, Pseudomonas aeruginosa which can cause wound suppuration, and Klebsiella pneumoniae which is the cause of pneumonia. Since the discovery of penicillin, many antibiotics have been reported in succession to exert excellent bactericidal effects for some time. However, some antibiotics have not been effective against bacteria due to the wide use and abuse of antibiotics, and new effective antibacterial agents are urgently needed to solve the situation.

From the structure of bacteria, the bacteria have cell walls and cell membranes, a plurality of proteins are contained in the cell walls and the cell membranes, the isoelectric points of the proteins are generally between 3 and 5, the external pH is generally neutral and is higher than the isoelectric points, so the proteins are negatively charged, and the bacteria are negatively charged under the general external conditions. Positively charged compounds such as those with groups such as quaternary ammonium salts, quaternary phosphonium salts, guanidinium salts, and pyridinium salts have been shown to electrostatically attract bacteria and thereby interfere with normal physiological activities of the bacteria to kill them. Since many antibacterial agents tend to damage normal cells during use, it is of great importance to develop efficient and low-toxic antibacterial agents.

Disclosure of Invention

Aiming at the problems, the invention provides a dinaphthyl pyridinium antibacterial material, a preparation method and application.

In order to achieve the purpose, the invention adopts the following technical scheme:

the antibacterial material of the dinaphthyl pyridinium has the structural formula as follows:

a preparation method of a dinaphthyl pyridinium antibacterial material comprises the following steps:

step 1, heating and vigorously stirring S-1,1' -bi-2-naphthol and acetone to obtain a uniform mixed solution, then adding 1, 4-di (bromomethyl) benzene and potassium carbonate into the mixed solution under the protection of inert gas, heating, refluxing and stirring, filtering a solid while the reaction is finished, extracting with dichloromethane and water, collecting an organic phase, drying with anhydrous sodium sulfate, removing the solvent in a vacuum rotary manner, and performing column chromatography on the obtained crude product by using dichloromethane/petroleum ether (1/3 (v/v) as an eluent to obtain 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl;

and 2, adding 2,2' -bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl and pyridine into DMF under the protection of nitrogen, heating to react under stirring, cooling to room temperature, adding into an acetone solution, filtering out a white solid after the white solid is separated out, washing with DMF, acetone and diethyl ether in sequence, and drying in vacuum to obtain 1,1' - ((((([ [ [ [ [1,1' -binaphthyl ] -2,2' -diylbis (oxy)) bis (methylene)) bis (4, 1-phenylene)) bis (methylene)) bis (pyridine-1) bromide, namely the binaphthyl pyridinium antibacterial material.

Further, the mass ratio of the S-1,1' -bi-2-naphthol to the acetone in the step 1 is 1: 18-1: 22;

in the step 1, the molar ratio of 1, 4-bis (bromomethyl) benzene to potassium carbonate is 3.5: 1-5: 1;

the volume ratio of the mixed solution, 1, 4-bis (bromomethyl) benzene and potassium carbonate in the step 1 is 6: 1-8: 1.

Further, the heating time of heating, refluxing and stirring in the step 1 is 6 hours;

the heating temperature for heating and violently stirring in the step 1 is 65 ℃, and the stirring time is 4-8 hours;

the heating temperature of the heating reaction in the step 2 is 70-80 ℃, and the reaction time is 48 h.

Further, the molar ratio of pyridine and 2,2 '-bis ((4- (bromomethyl) benzyl) oxy) -1,1' -binaphthyl to DMF in step 2 was 2:1: 86.5.

Further, the amount of DMF, acetone and ether washing is as follows: 150 mL-200 mL;

the temperature of the vacuum drying is 25 ℃, and the time is 48 h.

An application of the antibacterial material of dinaphthyl pyridinium in killing gram-negative bacteria.

Further, the gram-negative bacteria include escherichia coli, enterobacter cloacae, salmonella typhimurium, klebsiella pneumoniae, and pseudomonas aeruginosa.

An application method of a binaphthyl pyridinium antibacterial material determines the killing effect of gram-negative bacteria by a coating plate method, and has low damage to cells and low cytotoxicity under antibacterial concentration.

Compared with the prior art, the invention has the following advantages:

the invention discloses a preparation method and application of an antibacterial material containing a binaphthyl skeleton and a pyridinium functional group. The dinaphthalene pyridinium antibacterial material obtained by the invention is a low-toxicity and high-efficiency antibacterial material, has good antibacterial performance on various gram-negative bacteria, and has lower cytotoxicity. The material can be used as an antibacterial agent for treating bacterial infection. The preparation method is simple and has mild conditions.

Drawings

FIG. 1 shows an ultraviolet absorption spectrum and a fluorescence emission spectrum of the antibacterial material of the present invention in dimethyl sulfoxide;

FIG. 2 shows the results of the bactericidal test of the antibacterial material of the present invention against five gram-negative bacteria;

FIG. 3 shows the toxicity test results of the antibacterial material of the present invention against human cervical cancer cells;

FIG. 4 is a scanning electron micrograph of the antibacterial material of the present invention killing Escherichia coli.

Detailed Description