Cyclodextrin grafted N cation bornyl ester polymer antibacterial material and synthesis thereof

Abstract

The invention relates to a cyclodextrin grafted N cation bornyl ester polymer antibacterial material, which has the following structure: # imgabs0 #, wherein x is the number of structural units of N cation bornyl ester, namely the degree of polymerization, and x is equal to 20-100; x is one of F <->, Cl <->, Br <-> or I <->. Meanwhile, the invention further discloses a synthesis method of the macromolecular antibacterial material. The cyclodextrin grafted N cation bornyl ester polymer is a natural cyclic oligosaccharide antibacterial material grafted with natural active molecules, and the cyclodextrin grafted N cation bornyl ester polymer prepared through two simple steps has more efficient antibacterial activity, broad-spectrum antibacterial performance and good biocompatibility, and can be applied to the field of biomedicine. And preparing antibacterial materials such as fruit fresh-keeping materials, antibacterial coatings, antibacterial fabrics and the like.

Description

Technical Field

[0001] The invention relates to the technical field of synthesis of antibacterial functional polymer materials, in particular to a natural cyclic oligosaccharide antibacterial material grafted with natural active molecules, namely: a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material and its synthesis. Background Art

[0002] Bacteria are one of the main branches of pathogens, and most bacteria endanger human health and cause frequent public health incidents. According to data provided by the World Health Organization (WHO) in 2015, about 700,000 people die each year from drug-resistant bacteria such as "super bacteria". By 2050, this number is likely to exceed 10 million, exceeding the current number of deaths from cancer. Of course, harmful microorganisms such as bacteria are also not conducive to the normal development and growth of animals and plants. Therefore, how to effectively resist bacteria has become a research hotspot in the current scientific research fields such as materials science and biomedicine, and innovative research results have positive social significance and economic value.

[0003] Traditional antimicrobial agents include antibiotics (such as penicillin, cephalosporin, tetracycline, etc.), metal ions (such as Au + 、Ag + , Cu 2+etc.), organic cationic compounds (such as quaternary ammonium salts, quaternary phosphonium salts, hexamethyl argon arc, etc.). Among them, with the abuse of antibiotics, the emergence of drug-resistant bacteria has greatly reduced the effectiveness of antibiotics, the dosage has continued to increase, and it is also accompanied by great harm to the human body, and the cost has continued to rise. Cationic antibacterial agents have strong antibacterial ability and are not easy to develop drug resistance; especially quaternary ammonium salt antibacterial agents, because of their high potential and peptide-like structure, they have attracted widespread attention. For example: Xu Y, et al. (Synthesis, characterization, antifungal properties of quaternary ammonium salts derived from natural rosin, Biomass Conversion and Biorefinery, 2024, 14, 18803-18811.) synthesized rosin-derived quaternary ammonium salts and found that rosin acid-derived quaternary ammonium salts showed obvious antifungal activity and are expected to be used as bamboo mold inhibitors. Wei L,et al.(The antioxidant and antifungal activity of chitosan derivatives bearing Schiff bases and quaternary ammonium salts,Carbohydrate Polymers,2019,226,115256.)Quaternary ammonium salt chitosan derivatives were synthesized through the intermediate 6-O-chloroacetyl-2-N,N,N-trimethyl quaternary ammonium salt chitosan, and used for antifungal (Fusarium oxysporum), and found that its antifungal activity was enhanced and showed stronger antioxidant activity than chitosan.In short, N cationic antibacterial materials represented by quaternary ammonium salts have certain activity, but their high cytotoxicity limits their application areas.

[0004] As a class of biocompatible and biodegradable cyclic oligosaccharides, cyclodextrins have good surface activity. Because their structure belongs to the cage-like molecule family, they are easy to form inclusion complexes with other compounds or ions, and the internal hydrophobic cavity can encapsulate functional small molecules. Combining cyclodextrins with functional small molecules or functional polymers can improve their biocompatibility, such as: cyclodextrins can interact with N-acyl-L-homoserine lactone (AHL, a major signaling molecule in the bacterial intercellular communication quorum sensing system). Of course, the concept of complexing cyclodextrins with signaling molecules (AHLs or peptides) is not to kill bacteria, but to control bacterial growth and reduce their toxicity. When drugs are complexed with cyclodextrins, the surface active groups based on cyclodextrins can improve their performance. Khanna S, et al. (Mosquito repellent activity of cotton functionalized with inclusion complexes of β-cyclodextrin citrate and essential oils, International Journal of Interdisciplinary Research, 2018, 5, 1-18) found that β-cyclodextrin citrate was compounded with cedar, clove, eucalyptus, mint, lavender and jasmine essential oils to evaluate the properties of the encapsulation inclusion complex; Dong C, et al. (Antibacterial modification of cellulose fibers by grafting β-cyclodextrin and inclusion with ciprofloxacin, Cellulose, 2014, 21, 1921-1932) reported the preparation of antibacterial modified cellulose fibers by β-cyclodextrin encapsulated ciprofloxacin hydrochloride (CipHCl), revealing the loading and release behavior of CipHCl in β-CD grafted cellulose fibers, and observed that the release time of loaded CipHCl was prolonged, and the grafted fibers had much higher bacterial activity against Escherichia coli and Staphylococcus aureus; Ntoutoume GMAN, et al. al. (Development of curcumin-cyclodextrin / cellulose nanocrystals complexes: New anticancer drug delivery systems, Bioorganic & Medicinal Chemistry Letters, 2016, 26, 941-945) reported the synthesis of curcumin-cyclodextrin / cellulose nanocrystal nanocomplexes and found that the resulting complexes exerted antiproliferative effects on colorectal cancer cell lines and prostate cancer cell lines, IC50 (the half-inhibitory concentration of the measured antagonist) is lower than that of curcumin alone; Minodora A, et al. (Host-Guest interaction study of olmesartan medoxomil with β-cyclodextrin derivatives, Molecules, 2024, 29, 2209) reported that methylated β-cyclodextrin (RM-β-CD) was used to encapsulate Olmesartan Medoxomil (OLM). The molecular encapsulation of OLM in RM-β-CD increased the solubility of the drug, overcoming the limitation of poor water solubility in the treatment process. RM-β-CD can be used to design a new drug formulation containing OLM. Therefore, the use of cyclodextrin to encapsulate organic drugs in its internal cavity provides an ideal "hiding place" for these molecules, which can improve the biopharmaceutical profile, use cyclodextrin to enhance the water solubility of drugs, reduce their own toxicity, and have higher bioavailability.

[0005] As people pay more and more attention to health, the development and utilization of bio-based functional materials are becoming increasingly important, and antibacterial materials represented by plant essential oils have been widely recognized. Studies have found that borneol, a natural molecule extracted from the leaves of Lauraceae plants, has excellent antibacterial adhesion effects. For example: Yang L, et al. (Durable antibacterialcotton fabrics based on natural borneol-derived anti-MRSA agents, AdvancedHealthcare Materials, 2020, 9, 2000186.) Borneol is combined with hydrophilic poly (N,N-dimethylethyl methacrylate) polymer chains. Based on the antibacterial ability of borneol, it can be grafted onto cotton fabrics as a non-leaching antibacterial agent, thereby enhancing the antibacterial ability of borneol against Gram-negative, Gram-positive and even multidrug-resistant bacteria; Zhang P, et al. (Dual coordination between stereochemistry and cations endows polyethyleneterephthalate fabrics with diversiform antimicrobial abilities for attack and defense, ACS Applied Materials&Interfaces, 2023, 15, 9926-9939.) Borneol-4-formylbenzoate is introduced into cationic polymer-modified fabrics to enhance the antibacterial and anti-adhesion properties of the fabrics. In addition, most reports on borneol are based on its unique spatial structure and its targeting, such as: Invention patent CN110628011A discloses a phospholipid polyethylene glycol borneol polymer and its preparation method for achieving blood-brain barrier penetration function, which uses borneol as a functional molecule to achieve brain-targeted drug delivery and provides a preparation method for a brain-targeted drug delivery carrier; Invention patent CN118530291A discloses a breviscapine-borneol eutectic and its preparation method, the breviscapine-borneol eutectic prepared has good stability, sustained release characteristics, and can improve the in vitro transdermal performance of the poorly soluble drug breviscapine, thereby improving its bioavailability; Invention patent CN114231112 A discloses a bismuth vanadate / 3D graphene foam / acrylic acid boroisobornyl ester polymer-based composite coating and its preparation method, the pore structure formed by the hydrolysis of the acrylic acid boroisobornyl ester polymer can expose its interior, which can effectively improve the anti-fouling performance of the coating; Invention patent CN110724424 A discloses an antifouling coating for marine net lines and a preparation method thereof. The synthesized quaternary novel diisobutylene / n-pentyl acrylate / styrene / isobornyl methacrylate copolymer improves the antifouling ability of the coating.The above shows that borneol has great development potential in the fields of drug delivery, anti-bacterial adhesion, anti-fouling, etc. However, the direct use of borneol is limited to a certain extent by the hydrophobicity caused by its unique structure. Modifying borneol and expanding its application range is an interesting research direction.

[0006] The three-dimensional structure of borneol can prevent bacteria from adhering, which is the key to giving it antibacterial properties. In order to achieve better antibacterial effects of borneol-modified materials, antibacterial ability is given to them on the basis of borneol's anti-adhesion, so as to achieve the purpose of quickly killing microorganisms and preventing the formation of biofilms. This "attack and defense integrated" antibacterial and anti-adhesion strategy is a new antibacterial approach. The present invention first combines borneol with antibacterial and anti-adhesion functions with cationic antibacterial units to synthesize a new type of N-cationic borneol ester antibacterial monomer; secondly, a cyclodextrin-grafted small molecule chain transfer agent is used through reversible addition-fragmentation chain transfer (RAFT) polymerization technology to graft polymerize N-cationic borneol ester antibacterial monomers with biocompatible cyclodextrin to synthesize cyclodextrin-grafted N-cationic borneol ester polymer antibacterial materials. The polymer antibacterial material combines borneol and N cations and embeds them into the cyclodextrin grafted polymer chain, thereby creatively constructing a "attack and defense integrated" polymer antibacterial material. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material with excellent performance.

[0008] Another technical problem to be solved by the present invention is to provide a method for synthesizing the cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material.

[0009] In order to solve the above problems, the present invention discloses a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material, characterized in that the polymer antibacterial material has the following structure:

[0010]

[0011] Wherein: x is the number of structural units of N-cationic bornyl ester, i.e., the degree of polymerization, x=20 to 100; X - =F - , Cl - Br - or I - One of them.

[0012] The method for synthesizing the cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as described above comprises the following steps:

[0013] ⑴Synthesis of N-cationic Borneol Antibacterial Monomer:

[0014] In a container A equipped with a stirring device, borneol, a reaction solvent and a base are added in sequence, and stirred in an ice-water bath at 0-5°C for 10-30 minutes; then, a mixed solution of a haloacetyl halide reagent and a reaction solvent is added by slow dropwise addition, and after the dropwise addition is completed, the reaction is continued at low temperature for 1-3 hours; the ice-water bath is removed, and the temperature is raised to room temperature and the reaction is continued for 6-24 hours; saturated salt water is added to separate the organic phase, and anhydrous magnesium sulfate is added to filter it, and a crude product is obtained by rotary evaporation; the crude product is purified by column chromatography to obtain a product having an aromatic odor. The ratio of the borneol to the haloacetyl halide reagent is 10-40mmol:5-80mmol; the ratio of the borneol to the saturated saline solution is 10-40mmol:20-50mL; the ratio of the borneol to the anhydrous magnesium sulfate is 10-40mmol:2.0-3.5g;

[0015] In a container B equipped with a stirring and heating device, dimethylaminoethyl methacrylate, haloacetyl bornyl ester and a reaction solvent are added in sequence, and the reaction is carried out at 65-80°C for 12-48 hours under the protection of an inert gas; after the reaction is completed, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation, and the mixture is injected into a precipitant to precipitate the target product; the target product is filtered, washed and vacuum dried to obtain an off-white solid powder of N-cationic bornyl ester antibacterial monomer; the ratio of dimethylaminoethyl methacrylate, haloacetyl bornyl ester and the reaction solvent is 10-40mmol:10-40mmol:20-80mL; the ratio of haloacetyl bornyl ester to the precipitant is 10-40mmol:50-100mL;

[0016] (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material:

[0017] In a polymerization reactor, N-cationic bornyl ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent are added in sequence, stirred evenly, and the system is subjected to 3 to 6 cycles of freeze-thaw-vacuum-filling with inert gas. After the cycle is completed, the system is filled with inert gas and stirred in a heating bath at 70 to 85° C. for 18 to 36 hours. After the reaction is completed, the system is immersed in liquid nitrogen for quenching and thawing, and a precipitant is added to the system. The product is filtered and washed 3 to 5 times and collected. The product is subjected to 3 The product cyclodextrin grafted N cationic borneol ester polymer antibacterial material is obtained by vacuum drying at 0-60°C for 3-6h; the ratio of the N cationic borneol ester antibacterial monomer, the cyclodextrin grafted chain transfer agent, the initiator and the reaction solvent is 0.5-2.0g: 0.05-0.15g: 1.0-5.5mg: 10-25mL; the ratio of the N cationic borneol ester antibacterial monomer to the precipitant is 0.5-2.0g: 20-250mL.

[0018] In the step (1), the base refers to one of triethylamine, ammonia water and pyridine.

[0019] The mixed solution of the haloacetyl halide reagent and the reaction solvent in step (1) refers to a solution in which the haloacetyl halide reagent and the reaction solvent are uniformly mixed in a ratio of 5 to 80 mmol: 25 to 45 mL; the haloacetyl halide reagent refers to chloroacetyl chloride or bromoacetyl chloride.

[0020] In the step (1), the column chromatography uses neutral silica or alumina as the stationary phase and an ethyl acetate / petroleum ether mixture as the eluent; the volume ratio of ethyl acetate to petroleum ether in the ethyl acetate / petroleum ether mixture is 1:5 to 1:20.

[0021] The reaction solvents in step (1) and step (2) are both dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol, acetone, or a mixture of two thereof.

[0022] The precipitating agents in step (1) and step (2) are all one of ether, acetone, and n-hexane or a mixture of the two.

[0023] The inert protective gas in step (1) and step (2) is one of nitrogen, argon and carbon dioxide.

[0024] The cyclodextrin-based chain transfer agent in step (2) refers to a β-cyclodextrin single-arm chain transfer agent synthesized using cyclodextrin and 2-(dodecyl trithiocarbonate)-2-methylpropionic acid as raw materials.

[0025] In the step (2), the initiator is azobisisobutyronitrile (AIBN) or azobisisoheptanenitrile (ADVN).

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] 1. The cyclodextrin grafted N-cationic bornyl ester polymer prepared by the present invention has more efficient antibacterial activity, broad-spectrum antibacterial performance and good biocompatibility.

[0028] 2. The method of preparing cyclodextrin grafted N-cationic borneol ester polymer of the present invention has the characteristics of high reaction selectivity and conversion rate, simple and efficient reaction steps, good reaction substrate tolerance, etc., providing a novel strategy for the innovative development and use of borneol.

[0029] 3. The cyclodextrin grafted N-cationic bornyl ester polymer obtained by the present invention can be applied to the preparation of antibacterial coatings, coatings, fabrics and fruit preservation.

[0030] 4. The cyclodextrin grafted N-cationic borneol ester polymer prepared by the present invention improves the hydrophilicity of the natural active molecule - borneol, and has a new antibacterial mode of "attack and defense in one". BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The specific implementation modes of the present invention are further described in detail below in conjunction with the accompanying drawings.

[0032] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of chloroacetyl bornyl ester prepared in Example 1 of the present invention.

[0033] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the N-cationic bornyl ester prepared in Example 1 of the present invention.

[0034] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the cyclodextrin grafted N-cationic bornyl ester polymer prepared in Example 1 of the present invention.

[0035] Figure 4 The infrared spectra of the cationic bornyl ester (1) and the cyclodextrin-grafted N-cationic bornyl ester polymer (2) prepared in Example 1 of the present invention.

[0036] Figure 5 This is a scanning electron microscope image of the cyclodextrin grafted N-cationic bornyl ester prepared in Example 1 of the present invention.

[0037] Figure 6 This is the contact angle of the cyclodextrin grafted N-cationic bornyl ester prepared in Example 1 of the present invention.

[0038] Figure 7 The figure shows the effect of the cyclodextrin grafted N-cationic bornyl ester prepared in Example 1 of the present invention on the antibacterial rate of Escherichia coli and Staphylococcus aureus at a specific concentration. DETAILED DESCRIPTION

[0039] A cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material, the polymer antibacterial material has the following structure:

[0040]

[0041] Wherein: x is the number of structural units of N-cationic bornyl ester, i.e., the degree of polymerization, x=20 to 100; X - =F - , Cl - Br - or I - One of them.

[0042] The present invention first combines borneol with antibacterial and anti-adhesion functions with cationic antibacterial units to synthesize a novel N-cationic borneol ester antibacterial monomer; secondly, a small molecule chain transfer agent based on β-cyclodextrin is used to graft polymerize the N-cationic borneol ester antibacterial monomer with cyclodextrin with biocompatibility through reversible addition-fragmentation chain transfer (RAFT) polymerization technology to synthesize a cyclodextrin-grafted N-cationic borneol ester polymer antibacterial material. The specific process is as follows:

[0043] The synthesis method of the cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material comprises the following steps:

[0044] ⑴Synthesis of N-cationic Borneol Antibacterial Monomer:

[0045] In a container A equipped with a stirring device, borneol, reaction solvent and base are added in sequence, the ratio of borneol, reaction solvent and base is 10-40mmol:25-45mL:5-80mmol, and the base refers to one of triethylamine, ammonia water and pyridine. Stir in a 0-5℃ ice water bath for 10-30min; then slowly add a mixed solution of haloacetyl halide reagent and reaction solvent in a dropwise manner, the mixed solution of haloacetyl halide reagent and reaction solvent refers to a solution in which haloacetyl halide reagent and reaction solvent are uniformly mixed in a ratio of 5-80mmol:25-45mL; haloacetyl halide reagent refers to chloroacetyl chloride or bromoacetyl chloride, and the ratio of borneol to haloacetyl halide reagent is 10-40mmol:5-80mmol. After the addition is completed, the reaction is continued at low temperature for 1 to 3 hours; the ice water bath is removed, and the temperature is raised to room temperature and the reaction is continued for 6 to 24 hours; saturated salt water is added to separate and collect the organic phase, the ratio of borneol to saturated salt water is 10 to 40 mmol: 20 to 50 mL, and anhydrous magnesium sulfate is added for filtration, and the ratio of borneol to anhydrous magnesium sulfate is 10 to 40 mmol: 2.0 to 3.5 g; a crude product is obtained by rotary evaporation; the crude product is purified by column chromatography to obtain haloacetyl borneol ester as a bright yellow clear oily liquid with an aromatic odor. Column chromatography uses neutral silica or alumina as the stationary phase and ethyl acetate / petroleum ether mixture as the eluent; the volume ratio (mL / mL) of ethyl acetate to petroleum ether in the ethyl acetate / petroleum ether mixture is 1:5 to 1:20.

[0046] In a container B equipped with a stirring and heating device, dimethylaminoethyl methacrylate, haloacetyl borneol and a reaction solvent are added in sequence, and the ratio of dimethylaminoethyl methacrylate, the haloacetyl borneol and the reaction solvent is 10-40mmol:10-40mmol:20-80mL; react at 65-80°C for 12-48h under the protection of an inert gas; after the reaction is completed, cool to room temperature, remove the solvent by rotary evaporation, and inject into a precipitant, and the ratio of haloacetyl borneol to the precipitant is 10-40mmol:50-100mL; precipitate the target product; the target product is filtered, washed and vacuum dried to obtain an off-white solid powder of N-cationic borneol antibacterial monomer.

[0047] The structure of the N-cationic bornyl ester antibacterial monomer is as follows:

[0048]

[0049] (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material:

[0050] In a polymerization reactor, N-cationic bornyl ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent are added in sequence, the ratio of N-cationic bornyl ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent is 0.5-2.0g: 0.05-0.15g: 1.0-5.5mg: 10-25mL, the cyclodextrin-based chain transfer agent refers to a β-cyclodextrin single-arm chain transfer agent synthesized with cyclodextrin and 2-(dodecyl trithiocarbonate)-2-methylpropionic acid as raw materials, and the initiator is azobisisobutyronitrile (AIBN) or azobisisoheptanenitrile (ADVN). Stir evenly, and perform freeze-thaw-vacuum-inert gas cycle for 3 to 6 times. After the cycle is completed, fill the system with inert gas and stir in a heating bath at 70 to 85°C for 18 to 36 hours. After the reaction is completed, immerse in liquid nitrogen for quenching and thawing, add a precipitant to the system, and the ratio of N-cationic bornyl ester antibacterial monomer to precipitant is 0.5 to 2.0 g: 20 to 250 mL. Filter and wash 3 to 5 times and collect the product, which is vacuum dried at 30 to 60°C for 3 to 6 hours to obtain the product cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material.

[0051] During the whole reaction process, the reaction solvent is one of dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol, acetone or a mixture of two thereof. The precipitant is one of ether, acetone, n-hexane or a mixture of two thereof. The inert protective gas is one of nitrogen, argon and carbon dioxide.

[0052] Embodiment 1 A method for synthesizing a cyclodextrin-grafted N-cationic bornyl ester polymer antibacterial material comprises the following steps:

[0053] ⑴Synthesis of N-cationic Borneol Antibacterial Monomer:

[0054] In a round-bottom flask equipped with a stirring device, 10mmol borneol, 25mL dichloromethane and 5mmol triethylamine were added in sequence, and the mixture was placed in a 0℃ ice-water bath and stirred for 10min; then, 5mmol chloroacetyl chloride and 25mL dichloromethane were mixed evenly, and slowly added dropwise to the system, and the reaction was continued at low temperature for 1h; the ice-water bath was removed, the temperature was raised to room temperature, and the reaction was continued for 6h; 20mL saturated brine was added and the organic phase was collected by separation, and 2g anhydrous magnesium sulfate was added for filtration, and a crude product was obtained by rotary evaporation; the crude product was purified by column chromatography using ethyl acetate: petroleum ether = 1:5 (volume ratio) as the eluent, and finally a bright yellow clear oily liquid with an aromatic odor was obtained, namely chloroacetyl borneol ester.

[0055] Secondly, in a flask equipped with a stirring and heating device, 10 mmol of dimethylaminoethyl methacrylate, 10 mmol of chloroacetyl bornyl ester and 20 mL of acetonitrile were added in sequence, and the mixture was reacted at 65°C for 12 hours under nitrogen protection; after the reaction, the mixture was cooled to room temperature, the solvent was removed by rotary evaporation, and the mixture was injected into 50 mL of ether to precipitate the target product; after filtering and washing, the mixture was vacuum dried to obtain an off-white solid powder N-cationic bornyl ester antibacterial monomer.

[0056] (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material:

[0057] In a polymerization reactor, 0.50 g of N-cationic bornyl ester, 0.05 g of cyclodextrin grafted chain transfer agent, 1.0 mg of azobisisobutyronitrile and 10 mL of N,N-dimethylformamide were weighed and added in sequence, stirred evenly, and the system was subjected to three freeze-thaw-vacuum-nitrogen filling cycles. After the cycle was completed, the system was filled with nitrogen and stirred in a heating bath at 70°C for 18 hours; after the reaction was completed, it was immersed in liquid nitrogen for quenching and thawing, and 20 mL of ether was added to the system; the product was filtered and washed three times and collected, and vacuum dried at 30°C for 3 hours to obtain the product cyclodextrin grafted N-cationic bornyl ester polymer.

[0058] The target product (cyclodextrin grafted N-cationic bornyl ester polymer) and its intermediate (N-cationic bornyl ester antibacterial monomer) synthesized by the present invention were characterized and analyzed and tested for performance using the following methods:

[0059]

Nuclear magnetic resonance spectrum

[0060] Figure 1 The NMR spectrum of the synthesized chloroacetylated borneol ( 1 1H NMR). 1The positions and splitting conditions of the peaks in the H NMR spectrum are (CDCl3, 400MHz, δppm): 4.07 (d, 2H), 4.95-4.98 (dt, 1H), 2.38-2.41 (ddd, 2H), 1.91-1.95 (ddd, 1H), 1.43-1.69 (t, 2H), 1.24-1.31 (t, 2H), 0.85 (s, 3H), 0.87-0.9 (d, 3H). The results show that the chemical shift and integral ratio of each characteristic peak can correspond to the chemical structure of N-cationic bornyl ester antibacterial monomer, proving that the product structure is correct and pure, indicating that the target chloroacetylated bornyl was successfully prepared.

[0061] Figure 2 The NMR spectrum of the N-cationic bornyl ester antibacterial monomer ( 1 1H NMR). 1 The positions and splitting of the peaks in the H NMR spectrum are (CDCl3, 400 MHz, δ ppm): 4.06 (s, 1H), 5.63 (s, 1H), 1.91 (s, 3H), 4.98 (s, 2H), 4.23 (d, 2H), 4.37-4.42 (m, 2H), 4.93 (d, 1H), 3.74 (s, 3H), 1.16-1.37 (m, 7H), 0.85 (s, 3H), 0.87-0.9 (d, 3H). 1 H NMR showed that the chemical shift and integral ratio of each characteristic peak could correspond to the chemical structure of N-cationic bornyl ester antibacterial monomer, proving that the structure of the obtained product was correct and indicating that the N-cationic bornyl ester antibacterial monomer was successfully prepared.

[0062] Figure 3 The H NMR spectrum of the cyclodextrin grafted N-cationic bornyl ester polymer material ( 1 1H NMR). 1 The positions and splitting of the peaks in the H NMR spectrum are (CDCl3, 400 MHz, δ ppm): 2.94-2.86 (β-CD), 3.71, 4.92 (-CH2-), 3.43-3.48 (dd, N-CH3), 1.16-1.21 (t, -CH2-CH3), 0.87-0.9 (m, -CH3). 1 H NMR showed that the peaks of the obtained cyclodextrin grafted N-cationic bornyl ester polymer material were typical polymer broad peaks, and the chemical shift and integral ratio of each characteristic peak could correspond to its chemical structure, proving that the obtained structure was correct, indicating that the cyclodextrin grafted N-cationic bornyl ester polymer was successfully prepared.

[0063]

Infrared analysis spectrum

[0064] Figure 4The infrared spectra of N-cationic bornyl ester monomer (1) and cyclodextrin-grafted N-cationic bornyl ester polymer (2) are shown in FIG. -1 It is a strong absorption peak of ester carbonyl, with sharp peak shape and strong absorption; 2850~2995cm -1 It is the stretching and bending vibration of methyl and methylene; CN at 1630cm -1 Peak: 1045, 817cm -1 The presence of a six-membered ring epoxy compound confirmed the existence of cyclodextrin; in the N-cationic bornyl ester monomer spectrum at 1660 cm -1 The peak intensity of C=C is medium and obvious. There is no peak at this position in the spectrum of cyclodextrin grafted N-cationic bornyl ester polymer, indicating that the N-cationic bornyl ester monomer and cyclodextrin grafted N-cationic bornyl ester polymer were successfully synthesized.

[0065]

Microscopic morphology

[0066] Figure 5 This is a scanning electron microscope (SEM) image of the microscopic morphology of cyclodextrin grafted N-cationic bornyl ester polymer. SEM shows that the cyclodextrin grafted N-cationic bornyl ester polymer is irregular particles with a diameter of about 1 to 20 μm, and the surface is rough and porous, which increases the specific surface area of ​​the material and increases the probability of its contact with bacteria, making it easier to achieve the purpose of antibacterial.

[0067]

Contact angle

[0068] Figure 6 The figure is a contact angle diagram of cyclodextrin grafted N-cationic borneol ester polymer. It can be seen from the figure that the contact angle of the cyclodextrin grafted N-cationic borneol ester polymer is 31.78° (less than 90°), indicating that the cyclodextrin grafted N-cationic borneol ester polymer has strong hydrophilicity. It can be seen that the disadvantage of poor water solubility of borneol has been changed by cyclodextrin grafting, and it can play a better role in the antibacterial process.

[0069]

Antibacterial properties

[0070] Representative Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were selected as colonies, a certain amount of solid culture medium was prepared, and the antibacterial properties of cyclodextrin grafted N-cationic bornyl ester polymer were tested by a semi-qualitative colony counting method. Figure 7 The effect of cyclodextrin grafted N-cationic bornyl ester polymer on the antibacterial rate of E. coli and S. aureus; due to the presence of quaternary ammonium salt, N-cationic bornyl ester polymer exhibits significant antibacterial activity, and the antibacterial rate against E. coli exceeds 96% and can even reach 100%.

[0071] Example 2 A method for synthesizing a cyclodextrin-grafted N-cationic bornyl ester polymer antibacterial material comprises the following steps:

[0072] ⑴Synthesis of N-cationic Borneol Antibacterial Monomer:

[0073] In a round-bottom flask equipped with a stirring device, 20mmol borneol, 35mL dichloromethane and 30mmol triethylamine were added in sequence, and the mixture was placed in a 0℃ ice-water bath and stirred for 15min; 25mmol chloroacetyl chloride and 30mL dichloromethane were mixed evenly and slowly added dropwise to the system, and the reaction was continued at low temperature for 2h; the ice-water bath was removed, the temperature was raised to room temperature, and the reaction was continued for 12h; 30mL saturated brine was added and the organic phase was collected by separation, and 2.5g anhydrous magnesium sulfate was added for filtration, and a crude product was obtained by rotary evaporation; the crude product was purified by column chromatography using an eluent of ethyl acetate: petroleum ether in a volume ratio of 1:15 to obtain a bright yellow clear oily liquid with an aromatic odor, namely chloroacetyl borneol ester.

[0074] Secondly, in a flask equipped with a stirring and heating device, 25 mmol of dimethylaminoethyl methacrylate, 15 mmol of chloroacetyl borneol and 40 mL of acetonitrile were added in sequence, and the mixture was reacted at 70°C for 36 hours under nitrogen protection; after the reaction, the mixture was cooled to room temperature, the solvent was removed by rotary evaporation, and the mixture was injected into 80 mL of ether to precipitate the target product; after filtering and washing, the mixture was vacuum dried to obtain an off-white solid powder N-cationic borneol antibacterial monomer.

[0075] (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material:

[0076] In a polymerization reactor, 1 g of N-cationic bornyl ester, 0.15 g of cyclodextrin grafted chain transfer agent, 5 mg of azobisisobutyronitrile and 25 mL of N,N-dimethylformamide were added in sequence and stirred evenly. The system was subjected to three freeze-thaw-vacuum-nitrogen filling cycles. After the cycle was completed, the system was filled with nitrogen and stirred in a heating bath at 80°C for 24 hours. After the reaction was completed, it was immersed in liquid nitrogen for quenching and thawing, and 80 mL of ether was added to the system. The product was filtered and washed three times and collected, and then vacuum dried at 40°C for 5 hours to obtain the product cyclodextrin grafted N-cationic bornyl ester polymer.

[0077] Example 3 A method for synthesizing a cyclodextrin-grafted N-cationic bornyl ester polymer antibacterial material comprises the following steps:

[0078] ⑴Synthesis of N-cationic Borneol Antibacterial Monomer:

[0079] In a round-bottom flask equipped with a stirring device, 40mmol borneol, 45mL dichloromethane and 80mmol triethylamine were added in sequence, and the mixture was placed in a 5°C ice-water bath and stirred for 30min; 80mmol chloroacetyl chloride and 45mL dichloromethane were mixed evenly and slowly added dropwise to the system, and the reaction was continued at low temperature for 3h; the ice-water bath was removed, the temperature was raised to room temperature, and the reaction was continued for 8h; 50mL saturated brine was added and the organic phase was collected by separation, and 3.5g anhydrous magnesium sulfate was added for filtration, and a crude product was obtained by rotary evaporation; the crude product was purified by column chromatography using an eluent of ethyl acetate: petroleum ether in a volume ratio of 1:20 to obtain a bright yellow clear oily liquid with an aromatic odor, namely chloroacetyl borneol ester.

[0080] Secondly, in a flask equipped with a stirring and heating device, 40 mmol of dimethylaminoethyl methacrylate, 40 mmol of chloroacetyl borneol and 80 mL of acetonitrile were added in sequence, and the mixture was reacted at 80°C for 48 hours under nitrogen protection; after the reaction, the mixture was cooled to room temperature, the solvent was removed by rotary evaporation, and the mixture was injected into 100 mL of ether to precipitate the target product; after filtering and washing, the mixture was vacuum dried to obtain an off-white solid powder, namely N-cationic borneol antibacterial monomer.

[0081] (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material:

[0082] In a polymerization reactor, 2 g of N-cationic bornyl ester antibacterial monomer, 0.15 g of cyclodextrin grafted chain transfer agent, 5.5 mg of azobisisobutyronitrile and 25 mL of N,N-dimethylformamide were added in sequence and stirred evenly. The system was subjected to 6 freeze-thaw-vacuum-nitrogen filling cycles. After the cycle was completed, the system was filled with nitrogen and stirred in a heating bath at 85°C for 36 hours; after the reaction was completed, it was immersed in liquid nitrogen for quenching and thawing, and 250 mL of ether was added to the system; the product was filtered and washed 3 times and collected, and vacuum dried at 60°C for 6 hours to obtain the product cyclodextrin grafted N-cationic bornyl ester polymer.

Claims

1. A cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material, characterized in that: The polymer antibacterial material has the following structure: Wherein: x is the number of structural units of N-cationic bornyl ester, i.e., the degree of polymerization, x=20 to 100; X - =F - , Cl - Br - or I - One of them.

2. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 1, comprising the following steps: ⑴Synthesis of N-cationic Borneol Antibacterial Monomer: In a container A equipped with a stirring device, borneol, a reaction solvent and a base are added in sequence, and stirred in an ice-water bath at 0-5°C for 10-30 minutes; then, a mixed solution of a haloacetyl halide reagent and a reaction solvent is added by slow dropwise addition, and after the dropwise addition is completed, the reaction is continued at low temperature for 1-3 hours; the ice-water bath is removed, and the temperature is raised to room temperature and the reaction is continued for 6-24 hours; saturated salt water is added to separate the organic phase, and anhydrous magnesium sulfate is added to filter it, and a crude product is obtained by rotary evaporation; the crude product is purified by column chromatography to obtain a product having an aromatic odor. The ratio of the borneol to the haloacetyl halide reagent is 10-40mmol:5-80mmol; the ratio of the borneol to the saturated saline solution is 10-40mmol:20-50mL; the ratio of the borneol to the anhydrous magnesium sulfate is 10-40mmol:2.0-3.5g; In a container B equipped with a stirring and heating device, dimethylaminoethyl methacrylate, haloacetyl bornyl ester and a reaction solvent are added in sequence, and the reaction is carried out at 65-80°C for 12-48 hours under the protection of an inert gas; after the reaction is completed, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation, and the mixture is injected into a precipitant to precipitate the target product; the target product is filtered, washed and vacuum dried to obtain an off-white solid powder of N-cationic bornyl ester antibacterial monomer; the ratio of dimethylaminoethyl methacrylate, haloacetyl bornyl ester and the reaction solvent is 10-40mmol:10-40mmol:20-80mL; the ratio of haloacetyl bornyl ester to the precipitant is 10-40mmol:50-100mL; (2) Synthesis of cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material: In a polymerization reactor, N-cationic bornyl ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent are added in sequence, stirred evenly, and the system is subjected to 3 to 6 cycles of freeze-thaw-vacuum-filling with inert gas. After the cycle is completed, the system is filled with inert gas and stirred in a heating bath at 70 to 85° C. for 18 to 36 hours. After the reaction is completed, the system is immersed in liquid nitrogen for quenching and thawing, and a precipitant is added to the system. The product is filtered and washed 3 to 5 times and collected. The product is subjected to 3 The product cyclodextrin grafted N cationic borneol ester polymer antibacterial material is obtained by vacuum drying at 0-60°C for 3-6h; the ratio of the N cationic borneol ester antibacterial monomer, the cyclodextrin grafted chain transfer agent, the initiator and the reaction solvent is 0.5-2.0g: 0.05-0.15g: 1.0-5.5mg: 10-25mL; the ratio of the N cationic borneol ester antibacterial monomer to the precipitant is 0.5-2.0g: 20-250mL.

3. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: In the step (1), the base refers to one of triethylamine, ammonia water and pyridine.

4. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: The mixed solution of the haloacetyl halide reagent and the reaction solvent in step (1) refers to a solution in which the haloacetyl halide reagent and the reaction solvent are uniformly mixed in a ratio of 5 to 80 mmol: 25 to 45 mL; the haloacetyl halide reagent refers to chloroacetyl chloride or bromoacetyl chloride.

5. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: In the step (1), the column chromatography uses neutral silica or alumina as the stationary phase and an ethyl acetate / petroleum ether mixture as the eluent; the volume ratio of ethyl acetate to petroleum ether in the ethyl acetate / petroleum ether mixture is 1:5 to 1:

20.

6. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: The reaction solvents in step (1) and step (2) are both dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol, acetone, or a mixture of two thereof.

7. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: The precipitating agents in step (1) and step (2) are all one of ether, acetone, and n-hexane or a mixture of the two.

8. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: The inert protective gas in step (1) and step (2) is one of nitrogen, argon and carbon dioxide.

9. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: The cyclodextrin-based chain transfer agent in step (2) refers to a β-cyclodextrin single-arm chain transfer agent synthesized using cyclodextrin and 2-(dodecyl trithiocarbonate)-2-methylpropionic acid as raw materials.

10. The method for synthesizing a cyclodextrin grafted N-cationic bornyl ester polymer antibacterial material as claimed in claim 2, characterized in that: In the step (2), the initiator is azobisisobutyronitrile or azobisisoheptanenitrile.

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