A cyclodextrin grafted n-cationic borneol ester polymer antibacterial material and synthesis thereof

Abstract

The application relates to a cyclodextrin grafted N-cationic borneol ester polymer antibacterial material, which has the following structure: wherein x is the structural unit number of the N-cationic borneol ester, that is, the polymerization degree, x=20-100; X ‑ =F ‑ , Cl ‑ , Br ‑ or I ‑ . Meanwhile, the application also discloses a synthesis method of the polymer antibacterial material. The natural cyclic oligosaccharide antibacterial material grafted with natural active molecules has higher antibacterial activity, broad-spectrum antibacterial performance and good biocompatibility, can be applied to the biomedical field, and can be used for preparing fruit preservative materials, antibacterial coating, antibacterial fabric and other antibacterial materials.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of synthesis of antibacterial functional polymer materials, in particular to a natural cyclic oligosaccharide antibacterial material grafted with a natural active molecule, namely: a cyclodextrin grafted N-cationic borneol ester polymer antibacterial material and synthesis thereof. BACKGROUND

[0002] Bacteria are one of the main branches of pathogenic microorganisms, and most of them are harmful to human health and cause frequent public health incidents. According to the data provided by the World Health Organization (WHO) in 2015, about 700,000 people die from drug-resistant bacteria such as "super bacteria" every year, and this number may exceed 10 million by 2050, exceeding the number of people who die 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 fields of material science, biomedical science, etc., and innovative research results have positive social significance and economic value.

[0003] Traditional antibacterial 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.) and the like. Among them, with the abuse of antibiotics, the emergence of drug-resistant bacteria leads to a significant decrease in the effectiveness of antibiotics, and the dosage is constantly increasing, accompanied by great harm to the human body, and the cost is rising. Cationic antibacterial agents have strong antibacterial ability and are not easy to produce drug resistance; especially quaternary ammonium salt antibacterial agents, because of their high potential and peptide-like structure, they have received 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 were 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.) synthesized quaternary ammonium salt chitosan derivatives through intermediate 6-O-chloroacetyl-2-N,N,N-trimethyl quaternary ammonium salt chitosan, and used them for antifungal (Fusarium oxysporum), and found that their antifungal activity was enhanced, and they showed stronger antioxidant activity than chitosan. In summary, N-cationic antibacterial materials represented by quaternary ammonium salts have certain activity, but their high cytotoxicity limits their application field.

[0004] Cyclodextrins are biocompatible and biodegradable cyclic oligosaccharides with good surface activity. They belong to the family of cage-like molecules, which can form inclusion complexes with other compounds or ions. The hydrophobic cavity can encapsulate functional small molecules. Combining cyclodextrins with functional small molecules or functional polymers can improve their biocompatibility. For example, cyclodextrins can interact with N-acyl-L-homoserine lactone (AHL, a major signaling molecule of bacterial interspecies communication quorum sensing system). Of course, the concept of cyclodextrin complexing with signaling molecules (AHL or peptides) is not to kill bacteria, but to control bacterial growth and reduce their virulence. 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 complexed with cedar, clove, eucalyptus, peppermint, lavender and jasmine essential oils to evaluate the properties of the embedded 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 β-cyclodextrin complexed with ciprofloxacin hydrochloride (CipHCl) to modify antibacterial cellulose fibers. The loading and release behavior of CipHCl in β-CD grafted cellulose fibers was revealed, and it was 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 G.M.A.N., et 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 complexes. It was found that the resulting complexes exerted antiproliferative effects on colorectal and prostate cancer cell lines, with IC50 (Minodora A, et al. (Host-Guest interaction study of olmesartan medoxomil with β-cyclodextrin derivatives, Molecules, 2024, 29, 2209) reported the inclusion of olmesartan medoxomil (OLM) with methylated β-cyclodextrin (RM-β-CD), the molecular encapsulation of OLM in RM-β-CD resulted in an increase in the solubility of the drug, overcoming the limitations of poor water solubility during treatment, 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 "shelter" for these molecules, which can improve the biological pharmaceutical profile, and the use of cyclodextrin to enhance the water solubility of drugs, reduce their own toxicity, and have higher bioavailability.

[0005] With the increasing emphasis on 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 antibacterial cotton fabrics based on natural borneol-derived anti-MRSA agents, Advanced Healthcare Materials, 2020, 9, 2000186.) combined borneol with hydrophilic poly(N,N-dimethylacrylate) polymer chains, and based on the antibacterial ability of borneol, it can be grafted onto cotton fabrics as a non-leaching antibacterial agent, enhancing the antibacterial ability of borneol against gram-negative, gram-positive and even multi-drug resistant bacteria; Zhang P, et al. (Dual coordination between stereochemistry and cations endows polyethylene terephthalate fabrics with diversiform antimicrobial abilities for attack and defense, ACS Applied Materials & Interfaces, 2023, 15, 9926-9939.) introduced borneol-4-formylbenzoate into cationic polymer-modified fabrics, enhancing 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 properties. For example: Invention patent CN110628011A discloses a phospholipid polyethylene glycol borneol polymer that realizes the function of penetrating the blood-brain barrier and its preparation method. It uses borneol as a functional molecule for brain-targeted drug delivery and provides a preparation method for a brain-targeted drug delivery carrier; Invention patent CN118530291A discloses a scutellarein-borneol co-crystal and its preparation method. The prepared scutellarein-borneol co-crystal has good stability, slow-release characteristics, and can improve the in vitro transdermal performance of the poorly soluble drug scutellarein, thereby improving its bioavailability; Invention patent CN114231112 A discloses a bismuth vanadate / 3D graphene foam / propylene boron isobornylate polymer-based composite coating and its preparation method. The pore structure formed by the hydrolysis of propylene boron isobornylate polymer can expose its interior, effectively improving the antifouling performance of the coating; Invention patent CN110724424 A discloses a marine net line antifouling coating and its preparation method. The synthesized quaternary new diisobutylene / propylene n-pentyl acrylate / styrene / isobornyl methacrylate copolymer improves the antifouling ability of the coating.The above shows that borneol has great development potential in drug delivery, antibacterial adhesion, antifouling and other fields, but the direct use of borneol is limited to some extent due to the hydrophobicity caused by its unique structure. It is an interesting research direction to modify borneol and expand its application range.

[0006] The stereostructure of borneol can prevent bacterial adhesion, which is the key to its antibacterial property. In order to achieve better antibacterial effect of the modified borneol material, the antibacterial ability is endowed on the basis of the antibacterial adhesion of borneol to achieve the purpose of quickly killing microorganisms and preventing the generation of biofilm. This "offensive and defensive" antibacterial and anti-adhesion strategy is a new antibacterial approach. The present application first combines borneol with antibacterial and anti-adhesion functions with cationic antibacterial units to synthesize a novel N-cationic borneol ester antibacterial monomer; secondly, the N-cationic borneol ester antibacterial monomer is grafted and polymerized with cyclodextrin with biocompatibility by reversible addition-fragmentation chain transfer (RAFT) polymerization technology to synthesize a cyclodextrin grafted N-cationic borneol ester polymer antibacterial material. The high molecular antibacterial material combines borneol and N-cationic, and is embedded in the cyclodextrin grafted polymer chain, thereby creatively constructing a "offensive and defensive" high molecular antibacterial material. SUMMARY

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

[0008] Another technical problem to be solved by the present application is to provide a synthesis method of the cyclodextrin grafted N-cationic borneol ester polymer antibacterial material.

[0009] To solve the above problems, the cyclodextrin grafted N-cationic borneol ester polymer antibacterial material provided by the present application has the following structure:

[0010]

[0011] Wherein: x is the number of structure units of N-cationic borneol ester, that is, the degree of polymerization, x = 20-100; X - = F - , Cl - , Br - or I - .

[0012] The synthesis method of the cyclodextrin grafted N-cationic borneol ester polymer antibacterial material as described above comprises the following steps:

[0013] (1) Synthesis of N-cationic borneol ester antibacterial monomer:

[0014] In a container A equipped with stirring device, add the borneol, reaction solvent and base in turn, stir in ice water bath at 0-5℃ for 10-30 min; then add the mixed solution of halogen acetyl halide reagent and reaction solvent by slow dropwise, after dropwise addition, continue to react at low temperature for 1-3 h; remove the ice water bath, continue to react for 6-24 h after warming to room temperature; add saturated brine to collect the organic phase, and add anhydrous magnesium sulfate to filter, spin to get the crude product; the crude product is purified by column chromatography to obtain halogen acetyl borneol ester with aromatic smell, bright yellow clear oil liquid; the ratio of the borneol, the reaction solvent and the base is 10-40 mmol: 25-45 mL: 5-80 mmol; the ratio of the borneol and the halogen acetyl halide reagent is 10-40 mmol: 5-80 mmol; the ratio of the borneol and the saturated brine is 10-40 mmol: 20-50 mL; the ratio of the borneol and the anhydrous magnesium sulfate is 10-40 mmol: 2.0-3.5 g;

[0015] In a container B equipped with stirring and heating device, add dimethylaminoethyl methacrylate, halogen acetyl borneol ester and reaction solvent in turn, react at 65-80℃ under inert gas protection for 12-48 h; after the reaction is completed, cool to room temperature, spin to remove the solvent, and inject into the precipitator to precipitate the target product; the target product is filtered, washed and vacuum dried to obtain N-cation borneol ester antibacterial monomer in gray-white solid powder; the ratio of the dimethylaminoethyl methacrylate, the halogen acetyl borneol ester and the reaction solvent is 10-40 mmol: 10-40 mmol: 20-80 mL; the ratio of the halogen acetyl borneol ester and the precipitator is 10-40 mmol: 50-100 mL;

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

[0017] In the polymerization reactor, N-cation borneol ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent are added in sequence, stirred uniformly, the system is subjected to 3-6 times of freeze-thaw-vacuum-inert gas circulation, after the end of the circulation, the system is filled with inert gas, and stirred in a heating bath at 70-85℃ for 18-36h; after the reaction is completed, it is quenched by immersing in liquid nitrogen and thawing, a precipitant is added to the system; the product is collected after filtration, washing 3-5 times and vacuum drying at 30-60℃ for 3-6h, thereby obtaining the product cyclodextrin grafted N-cation borneol ester polymer antibacterial material; the ratio of the N-cation borneol ester antibacterial monomer, the cyclodextrin graft 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-cation borneol ester antibacterial monomer and the precipitant is 0.5-2.0g:20-250mL.

[0018] The base in the step 1 refers to one of triethylamine, ammonia and pyridine.

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

[0020] The column chromatography in the step 1 uses neutral silica or alumina as the stationary phase and 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 1:5-1:20.

[0021] The reaction solvent in the step 1 and the step 2 is one or a mixture of two of dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol and acetone.

[0022] The precipitant in the step 1 and the step 2 is one or a mixture of two of diethyl ether, acetone and n-hexane.

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

[0024] The cyclodextrin-based chain transfer agent in the step 2 refers to a β-cyclodextrin single-arm chain transfer agent synthesized from cyclodextrin and 2-(dodecyltrithio carbonate)-2-methylpropionic acid.

[0025] The initiator in the step 2 is azobisisobutyronitrile (AIBN) or azobisisoheptyl nitrile (ADVN).

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

[0027] 1. The cyclodextrin-grafted N-cationic borneol ester polymer prepared by this invention has more efficient antibacterial activity, broad-spectrum antibacterial properties and good biocompatibility.

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

[0029] 3. The cyclodextrin-grafted N-cationic borneol ester polymer obtained by this 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 this invention improves the hydrophilicity of the natural active molecule borneol, and has a new antibacterial mode of "attack and defense in one". Attached Figure Description

[0031] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0032] Figure 1 The image shows the 1H NMR spectrum of chloroacetyl borneol ester prepared in Example 1 of this invention.

[0033] Figure 2 The image shows the 1H NMR spectrum of the N-cationic borneol ester prepared in Example 1 of this invention.

[0034] Figure 3 The image shows the 1H NMR spectrum of the cyclodextrin-grafted N-cationic borneol ester polymer prepared in Example 1 of this invention.

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

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

[0037] Figure 6 The contact angle is that of the cyclodextrin-grafted N-cationic borneol ester prepared in Example 1 of this invention.

[0038] Figure 7 The effect of the cyclodextrin-grafted N-cationic borneol ester prepared in Example 1 of this invention on the antibacterial rate of Escherichia coli and Staphylococcus aureus at a specific concentration. Detailed Implementation

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

[0040]

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

[0042] The present application firstly combines borneol with antibacterial and anti-adhesion functions and cationic antibacterial units to synthesize a novel N-cationic borneol ester antibacterial monomer; secondly, a small molecular chain transfer agent taking β-cyclodextrin as the main body is used to graft polymerize the N-cationic borneol ester antibacterial monomer and cyclodextrin with biocompatibility through a 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 borneol ester polymer antibacterial material comprises the following steps:

[0044] (1) Synthesis of N-cationic borneol ester antibacterial monomer:

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

[0046] In a container B equipped with stirring and heating device, dimethylaminoethyl methacrylate, halogen acetyl borneol ester and reaction solvent were added in sequence, the ratio of dimethylaminoethyl methacrylate, halogen acetyl borneol ester and reaction solvent was 10-40 mmol: 10-40 mmol: 20-80 mL; under inert gas protection, the reaction was carried out at 65-80°C for 12-48h; after the reaction was completed, it was cooled to room temperature, the solvent was removed by rotary evaporation, and was injected into a precipitator, the ratio of halogen acetyl borneol ester and precipitator was 10-40 mmol: 50-100 mL; the target product was precipitated; after filtration, washing and vacuum drying, the N cation borneol ester antibacterial monomer in the form of gray-white solid powder was obtained.

[0047] The structure of the N cation borneol ester antibacterial monomer is as follows:

[0048]

[0049] 2. Synthesis of cyclodextrin grafted N cation borneol ester polymer antibacterial material:

[0050] In a polymerization reactor, N cation borneol ester antibacterial monomer, cyclodextrin grafted chain transfer agent, initiator and reaction solvent were added in sequence, the ratio of N cation borneol ester antibacterial monomer, cyclodextrin grafted chain transfer agent, initiator and reaction solvent was 0.5-2.0 g: 0.05-0.15 g: 1.0-5.5 mg: 10-25 mL, the cyclodextrin-based chain transfer agent refers to a β-cyclodextrin single-arm chain transfer agent synthesized from cyclodextrin and 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, and the initiator is azobisisobutyronitrile (AIBN) or azobisisoheptyl nitrile (ADVN). After uniform stirring, the system was subjected to 3-6 cycles of freezing-thawing-vacuum-inert gas filling, after the end of the cycle, the system was filled with inert gas, and was stirred in a heating bath at 70-85°C for 18-36h; after the reaction was completed, it was quenched by immersion in liquid nitrogen and thawed, a precipitator was added to the system, the ratio of N cation borneol ester antibacterial monomer and precipitator was 0.5-2.0 g: 20-250 mL. After filtration, washing 3-5 times and collection of the product, the product was vacuum dried at 30-60°C for 3-6h, to obtain the product cyclodextrin grafted N cation borneol ester polymer antibacterial material.

[0051] The reaction solvent throughout the reaction process was one or a mixture of two of dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol and acetone. The precipitator was one or a mixture of two of diethyl ether, acetone and n-hexane. The inert protective gas was one of nitrogen, argon and carbon dioxide.

[0052] Example 1, a synthesis method of a cyclodextrin grafted N cation borneol ester polymer antibacterial material, includes the following steps:

[0053] (1) Synthesis of N-cationic borneol ester antibacterial monomer:

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

[0055] Secondly, in a flask equipped with stirring and heating devices, 10 mmol of dimethylaminoethyl methacrylate, 10 mmol of chloroacetyl borneol ester and 20 mL of acetonitrile were sequentially added, and the reaction was carried out at 65°C for 12 h under nitrogen protection; after the reaction was completed, the temperature was cooled to room temperature, the solvent was removed by rotary evaporation, and the target product was precipitated by injecting into 50 mL of ether; after filtration and washing, the product was dried in vacuum to obtain a gray-white solid powder of N-cationic borneol ester antibacterial monomer.

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

[0057] In a polymerization reactor, 0.50 g of N-cationic borneol ester, 0.05 g of cyclodextrin grafting chain transfer agent, 1.0 mg of azobisisobutyronitrile and 10 mL of N,N-dimethylformamide were sequentially added, stirred uniformly, and the system was subjected to 3 cycles of freezing-thawing-vacuum-nitrogen filling, after which the system was filled with nitrogen and stirred in a heating bath at 70°C for 18 h; after the reaction was completed, the system was quenched in liquid nitrogen and thawed, 20 mL of ether was added to the system, and the product was collected by filtration, washing 3 times and drying in vacuum at 30°C for 3 h to obtain the product cyclodextrin grafted N-cationic borneol ester polymer.

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

[0059]

Nuclear magnetic resonance spectrum

[0060] Figure 1 The nuclear magnetic hydrogen spectrum (H NMR) of chloroacetylated borneol. 1 H NMR). 1The position and splitting of each peak in the H NMR spectrum are (CDCl3, 400 MHz, δ ppm): 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 the N-cationic borneol ester antibacterial monomer, proving that the obtained product has correct structure and is pure, and indicating that the target chloroacetylated borneol is successfully prepared.

[0061] Figure 2 The H NMR spectrum of the N-cationic borneol ester antibacterial monomer synthesized is shown in the following figure. 1 H NMR) spectrum. 1 The position and splitting of each peak 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 shows that the chemical shift and integral ratio of each characteristic peak can correspond to the chemical structure of the N-cationic borneol ester antibacterial monomer, proving that the obtained product has correct structure, and indicating that the N-cationic borneol ester antibacterial monomer is successfully prepared.

[0062] Figure 3 The H NMR spectrum of the N-cationic borneol ester antibacterial monomer synthesized is shown in the following figure. 1 HNMR) spectrum. 1 The position and splitting of each peak 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 shows that the peaks of the obtained N-cationic borneol ester polymer material grafted with cyclodextrin are typical polymer broad peaks, the chemical shift and integral ratio of each characteristic peak can correspond to its chemical structure, proving that the obtained structure is correct, and indicating that the N-cationic borneol ester polymer grafted with cyclodextrin is successfully prepared.

[0063]

Infrared analysis spectrum

[0064] Figure 4The infrared spectrum of N-cationic borneol ester monomer (1) and cyclodextrin grafted N-cationic borneol ester polymer (2). As can be seen from the figure, 1735 cm -1 is a strong absorption peak of ester carbonyl, the peak shape is sharp and the absorption is strong; 2850-2995 cm -1 is the stretching and bending vibration of methyl and methylene; C-N peaks at 1630 cm -1 ; 1045, 817 cm -1 indicate the presence of six-membered ring epoxide compounds, which confirms the presence of cyclodextrin; 1660 cm -1 C=C in the N-cationic borneol ester monomer spectrum, the peak intensity is moderate, and the peak is obvious, which indicates that the synthesis of N-cationic borneol ester monomer and cyclodextrin grafted N-cationic borneol ester polymer is successful.

[0065]

Micro-morphology

[0066] Figure 5 The scanning electron microscope (SEM) of the cyclodextrin grafted N-cationic borneol ester polymer micro-morphology. SEM shows that the cyclodextrin grafted N-cationic borneol ester polymer is an irregular particle with a diameter of about 1-20 μm, and the surface is rough and has pores, which increases the specific surface area of the material and increases the probability of contact with bacteria, making it easier to achieve antibacterial purposes.

[0067]

Contact angle

[0068] Figure 6 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 hydrophilic ability. As can be seen, the solubility of borneol in water is poor, which can better play a role in the antibacterial process.

[0069]

Antibacterial performance

[0070] Representative E. coli and S. aureus were selected as colonies, and a certain amount of solid medium was prepared. The antibacterial performance of cyclodextrin grafted N-cationic borneol ester polymer was tested by colony counting semi-quantitative method. Figure 7 The effect of cyclodextrin grafted N-cationic borneol ester polymer on the inhibition rate of E. coli and S. aureus; due to the presence of quaternary ammonium salt, N-cationic borneol ester polymer shows significant antibacterial activity, and the antibacterial rate of E. coli is more than 96%, even up to 100%.

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

[0072] 1. Synthesis of N-cationic borneol ester antibacterial monomer:

[0073] In a round-bottom flask equipped with a stirring device, 20 mmol of borneol, 35 mL of dichloromethane and 30 mmol of triethylamine were sequentially added, and stirred in an ice water bath at 0°C for 15 min; 25 mmol of chloroacetyl chloride and 30 mL of dichloromethane were mixed uniformly and slowly added to the system, and the reaction was continued for 2 h at low temperature; the ice water bath was removed, and the temperature was raised to room temperature, and the reaction was continued for 12 h; 30 mL of saturated brine was added and the organic phase was collected by liquid-liquid separation, and 2.5 g of anhydrous magnesium sulfate was added and filtered, and the crude product was obtained by rotary evaporation; the crude product was purified by column chromatography using ethyl acetate: petroleum ether = 1:15 as the eluent, and a clear yellowish oil with a fragrant odor was obtained, which was chloroacetyl borneol ester.

[0074] Secondly, in a flask equipped with stirring and heating devices, 25 mmol of dimethylaminoethyl methacrylate, 15 mmol of chloroacetyl borneol ester and 40 mL of acetonitrile were sequentially added, and the reaction was carried out at 70°C for 36 h under nitrogen protection; after the reaction was completed, the temperature was cooled to room temperature, the solvent was removed by rotary evaporation, and 80 mL of diethyl ether was injected to precipitate the target product; after filtration, washing and vacuum drying, the N-cationic borneol ester antibacterial monomer was obtained as a grayish white solid powder.

[0075] 2. Synthesis of cyclodextrin grafted N-cationic borneol ester polymer antibacterial material:

[0076] In a polymerization reactor, 1 g of N-cationic borneol ester, 0.15 g of cyclodextrin grafting chain transfer agent, 5 mg of azobisisobutyronitrile and 25 mL of N,N-dimethylformamide were sequentially added, stirred uniformly, and the system was subjected to 3 cycles of freezing-thawing-vacuum-nitrogen filling, after which the system was filled with nitrogen and stirred in a heating bath at 80°C for 24 h; after the reaction was completed, the system was quenched in liquid nitrogen and thawed, 80 mL of diethyl ether was added to the system, and the product was collected by filtration, washing 3 times and vacuum drying at 40°C for 5 h to obtain the product cyclodextrin grafted N-cationic borneol ester polymer.

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

[0078] 1. Synthesis of N-cationic borneol ester antibacterial monomer:

[0079] In a round bottom flask equipped with stirring device, 40 mmol borneol, 45 mL dichloromethane and 80 mmol triethylamine were added in turn, and stirred in 5 ℃ ice water bath for 30 min; 80 mmol chloroacetyl chloride and 45 mL dichloromethane were mixed uniformly and slowly dropped into the system, and the reaction was continued for 3 h at low temperature; the ice water bath was removed, and the temperature was increased to room temperature, and the reaction was continued for 8 h; 50 mL saturated brine was added, and the organic phase was collected by liquid-liquid separation, and 3.5 g anhydrous magnesium sulfate was added for filtration, and the crude product was obtained by rotary evaporation; the crude product was purified by column chromatography with ethyl acetate: petroleum ether = 1:20 as eluent, and a bright yellow clear oily liquid with aromatic odor was obtained, which was chloroacetyl borneol ester.

[0080] Secondly, in a flask equipped with stirring and heating device, 40 mmol dimethylaminoethyl methacrylate, 40 mmol chloroacetyl borneol ester and 80 mL acetonitrile were added in turn, and the reaction was carried out at 80 ℃ for 48 h under nitrogen protection; after the reaction was completed, the temperature was cooled to room temperature, the solvent was removed by rotary evaporation, and 100 mL ether was injected to precipitate the target product; after filtration and washing, the product was dried in vacuum to obtain a gray-white solid powder, which was N cationic borneol ester antibacterial monomer.

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

[0082] In a polymerization reactor, 2 g of N cationic borneol ester antibacterial monomer, 0.15 g of cyclodextrin grafting chain transfer agent, 5.5 mg of azobisisobutyronitrile and 25 mL of N,N-dimethylformamide were added in turn, and the system was stirred uniformly, and 6 cycles of freeze-thaw-vacuum-nitrogen filling were carried out, and after the cycles were completed, the system was filled with nitrogen and stirred in a heating bath at 85 ℃ for 36 h; after the reaction was completed, the system was quenched by immersing in liquid nitrogen and thawing, 250 mL of ether was added to the system, and the product was collected by filtration, washing 3 times and drying in vacuum at 60 ℃ for 6 h, to obtain the product cyclodextrin grafted N cationic borneol ester polymer.

Claims

1. A cyclodextrin grafted N-cationic borneol ester polymer antimicrobial material, characterized by: The polymer antibacterial material has the following structure: wherein: x is the number of structural units of N cation borne, i.e. the degree of polymerization, x = 20-100; X - = F - , Cl - , Br - or I - .

2. The synthesis method of the cyclodextrin grafted N-cationic borneol ester polymer antibacterial material according to claim 1, comprising the following steps:

1. Synthesis of N-cationic borneol ester antibacterial monomer: In a container A equipped with stirring device, borneol, reaction solvent and base are sequentially added, and stirred in an ice water bath at 0-5 DEG C for 10-30 min; then a mixture of halogen acetyl halide reagent and reaction solvent is added by slow dropwise addition, after dropwise addition is completed, the reaction is continued at low temperature for 1-3 h; remove the ice water bath, and continue to react at room temperature for 6-24 h; saturated brine is added to collect the organic phase, and anhydrous magnesium sulfate is added for filtration, and the crude product is obtained by rotary evaporation; the crude product is purified by column chromatography to obtain halogen acetyl borneol ester with aromatic odor, which is a bright yellow clear oil liquid; the ratio of the borneol, the reaction solvent and the base is 10-40 mmol: 25-45 mL: 5-80 mmol; the ratio of the borneol and the halogen acetyl halide reagent is 10-40 mmol: 5-80 mmol; the ratio of the borneol and the saturated brine is 10-40 mmol: 20-50 mL; the ratio of the borneol and the anhydrous magnesium sulfate is 10-40 mmol: 2.0-3.5 g; In a container B equipped with stirring and heating device, dimethylaminoethyl methacrylate, halogen acetyl borneol ester and reaction solvent are sequentially added, and reacted at 65-80 DEG C under inert gas protection for 12-48 h; after the reaction is completed, the system is cooled to room temperature, the solvent is removed by rotary evaporation, and the target product is precipitated by injecting into a precipitant; the target product is filtered, washed and vacuum dried to obtain N-cationic borneol ester antibacterial monomer in the form of off-white solid powder; the ratio of the dimethylaminoethyl methacrylate, the halogen acetyl borneol ester and the reaction solvent is 10-40 mmol: 10-40 mmol: 20-80 mL; the ratio of the halogen acetyl borneol ester and the precipitant is 10-40 mmol: 50-100 mL; 2. Synthesis of cyclodextrin grafted N-cationic borneol ester polymer antibacterial material: In a polymerization reactor, N-cationic borneol ester antibacterial monomer, cyclodextrin graft chain transfer agent, initiator and reaction solvent are sequentially added, stirred uniformly, and subjected to 3-6 cycles of freezing-thawing-vacuum-inert gas filling, after the cycles are completed, the system is filled with inert gas, and stirred in a heating bath at 70-85 DEG C for 18-36 h; after the reaction is completed, the system is quenched in liquid nitrogen and thawed, and a precipitant is added to the system; the product is collected after being filtered, washed 3-5 times, and vacuum dried at 30-60 DEG C for 3-6 h to obtain the product cyclodextrin grafted N-cationic borneol ester polymer antibacterial material; the ratio of the N-cationic borneol ester antibacterial monomer, the cyclodextrin graft chain transfer agent, the initiator and the reaction solvent is 0.5-2.0 g: 0.05-0.15 g: 1.0-5.5 mg: 10-25 mL; the ratio of the N-cationic borneol ester antibacterial monomer and the precipitant is 0.5-2.0 g: 20-250 mL.

3. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The base in step 1 refers to one of triethylamine, ammonia, and pyridine.

4. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The mixture of halogen acetyl halide reagent and reaction solvent in step 1 refers to a solution of halogen acetyl halide reagent and reaction solvent mixed uniformly in a ratio of 5-80 mmol: 25-45 mL; the halogen acetyl halide reagent refers to chloroacetyl chloride or bromoacetyl chloride.

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

20.

6. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The reaction solvent in step 1 and step 2 is one of dichloromethane, acetonitrile, N,N-dimethylformamide, anhydrous ethanol, and acetone, or a mixture of two of them.

7. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The precipitant in step 1 and step 2 is one of diethyl ether, acetone, and n-hexane, or a mixture of two of them.

8. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The inert 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 borneol polymer antibacterial material as described in claim 2, characterized in that: The cyclodextrin graft chain transfer agent in step 2 refers to a β-cyclodextrin single-arm chain transfer agent synthesized from cyclodextrin and 2-(dodecyltrithiocarbonate)-2-methylpropionic acid.

10. The method for synthesizing a cyclodextrin-grafted N-cationic borneol polymer antibacterial material as described in claim 2, characterized in that: The initiator in step 2 is azobisisobutyronitrile or azobisisoheptyl nitrile.

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