A cyclic cyclodextrin-grafted polyvanillin antibacterial material and its synthesis method

Abstract

This invention relates to a cyclic cyclodextrin-grafted polyvanillin antibacterial material, which has the following structure: where m is the number of structural units of the cyclodextrin, i.e., m=3, m=3.5, or m=4; R1 is -CN or -CH3; R2 is -H or -CH3; x is 0 or 2; n is the grafting degree; y is the number of structural units of the vanillin-derived monomer; and the product of y and n is the degree of polymerization. The invention also discloses a method for synthesizing this antibacterial material. The cyclodextrin-grafted polyvanillin prepared by this invention exhibits good biocompatibility, increases the solubility of polyvanillin in water, and enhances the antibacterial properties of polyvanillin.

Description

Technical Field

[0001] This invention relates to the fields of materials science and antibacterial technology, and in particular to a cyclic cyclodextrin-grafted polyvanillin antibacterial material and its synthesis method. Background Technology

[0002] To date, bacterial infections have become a leading cause of various diseases and an increased risk of illness worldwide, even directly or indirectly contributing to rising mortality rates. With the development of antibiotics, the incidence and severity of diseases induced by bacterial infections have been effectively controlled. However, the uncontrolled overuse of antibiotics can lead to bacterial resistance, resulting in superbugs. Therefore, researchers have developed inorganic nanoparticles (but these are costly and highly toxic), volatile and easily decomposed small organic molecules, and chemically unstable and weakly antibacterial natural polymers as alternatives to antibiotics to inhibit bacterial infections. Given the limitations of the aforementioned antibacterial materials, synthetic polymeric antibacterial materials not only possess good chemical stability and excellent antibacterial properties but also offer advantages such as low cost and high utilization rate. However, the preparation of synthetic polymeric antibacterial materials with good biocompatibility remains an urgent problem.

[0003] Natural vanillin, extracted from vanilla beans, possesses aldehyde and hydroxyl groups, and its functional groups facilitate modification and reuse. Biomass vanillin extracted from lignin exhibits low toxicity and renewable properties (CN 112251390A). Vanillin-derived monomers can replace harmful, volatile, and carcinogenic petroleum-based monomers such as styrene (L. Zhang, et al. A sustainable waterborne vanillin-eugenol-acrylate miniemulsion with suitable antibacterial properties as a substitute for the styrene-acrylateemulsion[J]. Green Chem., 2021, 23: 7576-7588.). Notably, the aldehyde group of vanillin-derived monomers endows them with antibacterial, antioxidant, and preservative properties. Despite exhibiting various properties, vanillin-based homopolymers suffer from severe aggregation due to the stacking of their benzene ring structures (π-π interactions), which renders most of the active groups trapped within the homopolymer and unable to function. As is well known, the hydrophobic benzene ring structure of vanillin has poor solubility in aqueous media (M.Abla, et al. Synthesis and evaluation of anticancer activity of hyaluronic acid / vanillin conjugates [J]. Macromol. Chem. Phys., 2022, 223:2200190.). Especially with the continuous increase and stacking of benzene rings after polymerization, the homopolymer exhibits obvious particulate insoluble matter in aqueous media, and the homopolymer cannot swell or dissolve, failing to expose its active groups. Therefore, designing host materials that can reduce the stacking of benzene ring structures and improve the water solubility of vanillin-based homopolymers to fully expose the active sites on the benzene rings is currently a hot research topic.

[0004] Clearly, macrocyclic hosts with hydrophilic exteriors and hydrophobic interiors can form host-guest interactions with hydrophobic guests. For example, biocompatible cyclodextrins can form classic host-guest encapsulations with adamantane (CN 115160454A) or styrene (X. Chen, et al. Direct synthesis of polymer nanotubes by aqueous dispersion polymerization of a cyclodextrin / styrene complex [J]. Angew. Chem.Int. Ed., 2017, 56: 16541-16545.) via hydrophobic interactions, attributable to enantioselective size matching. The host-guest interaction between cyclodextrins and hydrophobic structures enhances the solubility of hydrophobic substances in aqueous media. More importantly, the cyclodextrin-based host molecule can largely modulate the rigidity of the hydrophobic guest on the polymer chain, enabling the spontaneous formation of nanoassemblies with outstanding properties through host-guest mediation. In addition, cyclodextrins rich in hydroxyl groups, acting as the core of star polymers, can be chemically modified with carboxyl-containing chain transfer agents (CTAs) to form multi-armed bridges, allowing functionalized monomers to be embedded into CTAs (CN 116693721A). The spatial confinement effect of nanochannels can also limit the formation of long-sized linear polymers from monomers with benzene ring structures at high conversion rates (H.Pan, et al. Synthesis of darrowly distributed cyclic polymers by suzuki cross-coupling polycondensation undernanoconfinement [J]. Macromol., 2023, 56(23): 9523-9529.). However, the limited nanocavities of the cyclodextrin-based macromolecular chain transfer agent hinder the host-guest interaction between it and the hydrophobic blocks on the CTA, and the high degree of polymerization of the hydrophobic units fails to achieve the host-guest interaction between them. The multibranching of cyclodextrin-based star polymers increases the entanglement and steric hindrance of the branches, which is detrimental to the host-guest interaction between the hydrophobic components on the CTA and the cyclodextrin cavity. Therefore, controlling the low degree of polymerization of the hydrophobic blocks of the cyclodextrin arms and the low degree of branching of the cyclodextrin is a new strategy to achieve a win-win situation in terms of the degree of polymerization and grafting of cyclodextrin-based macromolecular chain transfer agents.

[0005] Reversible addition-fragmentation chain transfer radical polymerization (RAFT) is a general method with reversible chain transfer reactions and controllable degree of polymerization, often used to prepare nanomaterials of various shapes. Cyclic polymers are a class of end-to-end polymeric materials with cyclic structures. Compared with linear polymers, cyclic polymers exhibit better stability, slower degradation rates, smaller hydrodynamic volumes, and higher glass transition temperatures (T. Josse, et al. Cyclic polymers byring-closure strategies [J]. Angew. Chem. Int. Ed., 2016, 55: 13944-13958.). Due to their smaller hydrodynamic volume and compact cyclic structure, cyclic cationic copolymers exhibit superior antibacterial properties compared to their linear cationic copolymers, and their cytotoxicity is lower than that of linear cationic copolymers (J. Xu, et al. Antibacterial properties of synthesized cyclic and linear cationic copolymers[J]. Polym. Chem., 2020, 11: 6632-6639.). Cyclic polymer brushes composed of galactose units possess an extended topological structure, increasing the exposure of surface galactose units and demonstrating higher protein-binding ability than linear polymer brushes of the same molecular weight and composition (L. Trachsel, et al. Functional nanoassemblies of cyclic polymers show amplified responsiveness and enhanced protein-binding ability [J]. ACS Nano, 2020, 14(8):10054-10067.). Compared to linear polymers, cyclic polymers grafted onto nanoparticles result in nanoparticles with extremely high stability and excellent antifouling properties (B. Verbraeken, R. Hoogenboom. Cyclic polymers: from scientific curiosity to advanced materials for gene delivery and surface modification [J]. Angew. Chem.Int. Ed., 2017,56: 2-5.).Currently, methods for synthesizing cyclic polymers with clear topological structures and tunable sizes include: monomolecular / bimolecular ring-closure and ring-expansion methods (F. Haque, S. Grayson. The synthesis, properties and potential applications of cyclic polymers [J]. Nat. Chem., 2020, 12: 433-444.). Monomolecular ring-closure involves coupling the two ends of a linear polymer in dilute solution, transforming it into a cyclic polymer. Bimolecular ring-closure refers to the coupling reaction between a linear polymer containing functional groups at both ends and a coupling agent with two different functional groups. Ring-expansion involves continuously introducing cyclic monomers into a cyclic initiator or catalyst to expand the cyclic polymer. Besides covalent ring closure and expansion, supramolecular chemistry is another method for synthesizing polymers with variable topological structures. Typically, the construction of supramolecular chemistry relies on non-covalent interactions, including π-π interactions, electrostatic interactions, hydrogen bonding interactions, and host-guest interactions. The synthesis of topologically variable polymers using supramolecular chemistry is based on weak non-covalent interactions, allowing the conversion of polymers with one topological structure to another. Over the past decade, Takata's team has systematically developed several rotaxanes and crown ethers that slide and lock on polymer backbones with ammonium salt groups, enabling the transformation from linear to cyclic polymers, the reversible transition between linear and cyclic polymers, and the transformation from star polymers to linear polymers through host-guest recognition (T. Takata. Switchable polymer materials controlled by potaxane macromolecular switches [J]. ACS Cent. Sci., 2020, 6:129-143.). In addition, cyclodextrin-based polymer single chains can self-assemble into multiblock copolymers in the organic phase through host-guest interactions, realizing the use of organic solvents as the reaction medium for host-guest self-assembly, which further improves the intercalation capability of guest groups into cavities (AF Hirschbiel, et al. Access to multiblock copolymers via supramolecular host-guest chemistry and photochemical ligation [J]. ACS Macro.Lett., 2015, 4:1062-1066.).In aqueous solution, the azodiphenyl group at the end of the cyclodextrin-based polymer single chain can be controlled by thermochemical and photochemical processes to form different types of cyclic polymers with the cyclodextrin cavity (Y. Inoue, et al. Thermal and photochemical switching of conformation of poly(ethylene glycol)-substituted cyclodextrin with an azobenzene group at the chain end [J]. J.Am. Chem. Soc., 2007, 129: 6396-6397.). Combined with controlled / living polymerization, in aqueous solution, the reversible folding of the cyclodextrin-based polymer single chain can be driven by host-guest chemistry, and polymer rings can be synthesized by complexing with the terminal adamantyl group (J. Willenbacher. Reversible single-chain selective point folding via cyclodextrin-driven host-guest chemistry in water [J]. Chem. Commun., 2014, 50: 7056-7059.). However, existing host-guest interactions between cyclodextrin-based polymer chains and their hydrophobic guest molecules in organic phases cannot self-assemble into cyclic polymers. Furthermore, studies on the self-assembly of cyclic polymers between cyclodextrin-based polymer chains and their hydrophobic monomers (non-terminal groups) in organic phases have not been reported. Therefore, constructing "ring-like" polymers of cyclodextrin-based polymer chains and their hydrophobic monomers in organic phases through host-guest interactions remains a significant challenge. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a high-performance finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0007] Another technical problem to be solved by the present invention is to provide a method for synthesizing the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0008] To address the aforementioned problems, the present invention provides a cyclic cyclodextrin-grafted polyvanillin antibacterial material, characterized in that the antibacterial material has the following structure:

[0009]

[0010] Where: m is the number of structural units of the cyclodextrin, i.e., m=3, m=3.5 or m=4; R1 is -CN or -CH3; R2 is -H or -CH3; x is 0 or 2; n is the degree of grafting; y is the number of structural units of the vanillin-derived monomer; the product of y and n is the degree of polymerization.

[0011] The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described above includes the following steps:

[0012] (1) Preparation of cyclodextrin-based macromolecular chain transfer agents:

[0013] In a container equipped with a stirring, heating bath, and gas protection device, an amide solvent and cyclodextrin are added. Under a nitrogen atmosphere, the mixture is heated to 45-65 °C and slowly stirred until completely dissolved. After the resulting solution has cooled to room temperature, a RAFT chain transfer agent, a carbodiimide condensing agent, and a pyridine catalyst are added sequentially. The mixture is then sealed and magnetically stirred at 20-50 °C for 20-36 h, followed by a water bath at -5-25 °C for 1-5 h to complete the reaction. After vacuum filtration, a bright yellow liquid is obtained. This bright yellow liquid is added dropwise to an ether solvent and then vacuum filtered to obtain precipitate A. Precipitate A is then vacuum dried at 40-75 °C to constant weight to obtain a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent.

[0014] (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material:

[0015] Cyclodextrin-based macromolecular chain transfer agent, vanillin-derived monomer, oil-soluble initiator, and amide solvent were added to a container and magnetically stirred to mix the reaction substrate evenly. Subsequently, the sealed container was immersed in liquid nitrogen and subjected to several freeze-thaw cycles, with the system filled with inert gas during the last cycle. Then, the reaction was stirred in an oil bath at 60-90 °C for 15-25 h. After the reaction was completed, the container was immersed in liquid nitrogen to quench the reaction. After thawing, an ether solvent was added to the solution to precipitate the product, which was then obtained by vacuum filtration. Precipitate B was dried under vacuum at 45-75 °C to constant weight to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0016] In step (1), the ratio of amide solvent to cyclodextrin is 25-50 mL: 3.10-4.60 g; the ratio of ether solvent to cyclodextrin is 60-120 mL: 3.10-4.60 g.

[0017] In step (1), the RAFT chain transfer agent is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid or 4-cyano-4-[(dodecylthiocarbonylthiocarbonyl)thioalkyl]valerate, and the mass ratio of the RAFT chain transfer agent to cyclodextrin is 0.90~5.50 g: 3.10~4.60 g.

[0018] In step (1), the carbodiimide condensing agent is one of N,N-diisopropylcarbodiimide, N,N-dicyclohexylcarbodiimide, or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and the mass ratio of the carbodiimide condensing agent to cyclodextrin is 2.00 ~ 5.50 g: 3.10 ~ 4.60 g.

[0019] In step (1), the pyridine catalyst is pyridine or 4-dimethylaminopyridine, and the mass ratio of the pyridine catalyst to cyclodextrin is 0.35 ~ 0.55 g: 3.10 ~ 4.60 g.

[0020] In step (2), the mass ratio of amide solvent to cyclodextrin-based macromolecular chain transfer agent is 1.00 ~ 3.50 g : 50 ~ 250 mg; the ratio of ether solvent to cyclodextrin-based macromolecular chain transfer agent is 50 ~ 110 mL : 50 ~ 250 mg.

[0021] The amide solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylformamide; the ether solvent is one of petroleum ether, isopropyl ether, or diethyl ether.

[0022] In step (2), the vanillin-derived monomer is vanillin methacrylate or vanillin acrylate, and the mass ratio of the vanillin-derived monomer to the cyclodextrin-based macromolecular chain transfer agent is 200-500 mg: 50-250 mg.

[0023] In step (2), the oil-soluble initiator is one of azobisisobutyronitrile, azobisisoheptanenitrile, or dimethyl azobisisobutyrate, and the mass ratio of the oil-soluble initiator to the cyclodextrin-based macromolecular chain transfer agent is 0.67 ~ 6.70 mg: 50 ~ 250 mg.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] 1. This invention prepares a cyclodextrin-based macromolecular chain transfer agent by chemically modifying CTA with cyclodextrin, which has good biocompatibility. Subsequently, RAFT polymerization is used to synthesize cyclodextrin-grafted polyvanillin using vanillin-derived monomers with renewable properties. Finally, through host-guest interactions in the organic phase, the cyclodextrin-based polymer chain and the vanillin-derived monomer of the polymer chain self-assemble to prepare a novel finger-shaped cyclodextrin-grafted polyvanillin antibacterial material with good biocompatibility.

[0026] 2. This invention uses organic solvents as reaction media to construct cyclic cyclodextrin-grafted polyvanillin homopolymers through host-guest interactions, thus expanding the range from aqueous self-assembled cyclic polymers to organic self-assembled cyclic polymers. Furthermore, it achieves a breakthrough in the self-assembly of cyclic polymer chains with vanillin-derived monomers (non-terminal groups) on the polymer chains into cyclic polymers.

[0027] 3. This invention utilizes the host-guest interaction between the low-grafting-degree cyclodextrin-based polymer chain and the low-polymerization-degree polymer chain of vanillin to reduce the stacking of vanillin structure, thereby embedding the hydrophobic benzene ring structure in the hydrophobic cavity, improving the water solubility of the vanillin-based homopolymer, and fully exposing the active sites of the cyclodextrin-grafted polyvanillin, thus enhancing its antibacterial properties in the aquatic environment. Attached Figure Description

[0028] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0029] Figure 1 The nuclear magnetic resonance (NMR) hydrogen spectrum of the cyclodextrin-based macromolecular chain transfer agent and the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in Example 1 of this invention ( 1 (H NMR) image.

[0030] Figure 2 The image shows the Fourier transform infrared (FT-IR) spectrum of the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in Example 1 of this invention.

[0031] Figure 3 This is a macroscopic photograph of the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in Example 1 of the present invention.

[0032] Figure 4 This is a scanning electron microscope (SEM) image of the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in Example 1 of the present invention.

[0033] Figure 5 Photographs of antibacterial plates against Escherichia coli and Staphylococcus aureus using the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in Example 1 of this invention. Detailed Implementation

[0034] A cyclic cyclodextrin-grafted polyvanillin antibacterial material has the following structure:

[0035]

[0036] Where: m is the number of structural units of cyclodextrin, i.e., m=3 (α-cyclodextrin), m=3.5 (β-cyclodextrin), or m=4 (γ-cyclodextrin); R1 is -CN or -CH3; R2 is -H or -CH3; x is 0 or 2; n is the grafting degree; y is the number of structural units of vanillin-derived monomers; and the product of y and n is the degree of polymerization.

[0037] A method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material includes the following steps:

[0038] (1) Preparation of cyclodextrin-based macromolecular chain transfer agents:

[0039] In a container equipped with a stirring, heating bath, and gas protection device, an amide solvent and cyclodextrin are added. Under a nitrogen atmosphere, the mixture is heated to 45-65 °C and slowly stirred until completely dissolved. After the resulting solution has cooled to room temperature, a RAFT chain transfer agent, a carbodiimide condensing agent, and a pyridine catalyst are added sequentially. The mixture is then sealed and magnetically stirred at 20-50 °C for 20-36 h, followed by a water bath at -5-25 °C for 1-5 h to complete the reaction. The white precipitate is removed by vacuum filtration, yielding a bright yellow liquid. The bright yellow liquid is added dropwise to an ether solvent to precipitate the product. The precipitate A is obtained by vacuum filtration. Precipitate A is dried under vacuum at 40-75 °C to constant weight, yielding a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent.

[0040] The ratio of amide solvent to cyclodextrin is 25-50 mL: 3.10-4.60 g; the ratio of ether solvent to cyclodextrin is 60-120 mL: 3.10-4.60 g.

[0041] The RAFT chain transfer agent is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid or 4-cyano-4-[(dodecylthiocarbonylthiocarbonyl)thioalkyl]valeric acid, and the mass ratio of the RAFT chain transfer agent to cyclodextrin is 0.90 ~ 5.50 g : 3.10 ~ 4.60 g.

[0042] The carbodiimide condensing agent is one of N,N-diisopropylcarbodiimide, N,N-dicyclohexylcarbodiimide, or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and the mass ratio of the carbodiimide condensing agent to cyclodextrin is 2.00~5.50 g: 3.10~4.60 g.

[0043] The pyridine catalyst is pyridine or 4-dimethylaminopyridine, and the mass ratio of the pyridine catalyst to cyclodextrin is 0.35 ~ 0.55 g : 3.10 ~ 4.60 g.

[0044] The structure of the obtained cyclodextrin-based macromolecular chain transfer agent is shown below:

[0045]

[0046] (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material:

[0047] Cyclodextrin-based macromolecular chain transfer agent, vanillin-derived monomer, oil-soluble initiator, and amide solvent are added to a container (such as a Schlenk tube), and the reaction substrate is mixed homogeneously by magnetic stirring. Subsequently, the sealed container is immersed in liquid nitrogen and subjected to several freeze-thaw cycles, with the final cycle involving the filling of the system with inert gas. The specific freeze-thaw process is as follows: after the solvent is completely frozen, the stopcock is opened to create a vacuum for 2–9 minutes; the reaction flask is then closed, and thawing is allowed until the solvent is completely thawed. This process is repeated 2–6 times.

[0048] Then, the reaction was stirred in an oil bath at 60-90°C for 15-25 h. After the reaction was completed, the container was immersed in liquid nitrogen to quench the reaction. After thawing, an ether solvent was added to the solution to precipitate the product. The precipitate B was obtained by vacuum filtration. The precipitate B was dried under vacuum at 45-75°C to constant weight to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0049] The mass ratio of amide solvent to cyclodextrin-based macromolecular chain transfer agent is 1.00 ~ 3.50 g : 50 ~ 250 mg; the ratio of ether solvent to cyclodextrin-based macromolecular chain transfer agent is 50 ~ 110 mL : 50 ~ 250 mg.

[0050] The vanillin-derived monomer is vanillin methacrylate or vanillin acrylate, and the mass ratio of the vanillin-derived monomer to the cyclodextrin-based macromolecular chain transfer agent is 200-500 mg: 50-250 mg.

[0051] The oil-soluble initiator is one of azobisisobutyronitrile, azobisisoheptanenitrile, or dimethyl azobisisobutyrate, and the mass ratio of the oil-soluble initiator to the cyclodextrin-based macromolecular chain transfer agent is 0.67 ~ 6.70 mg: 50 ~ 250 mg.

[0052] The amide solvent used in the synthesis process is one of N,N-dimethylformamide, N,N-dimethylacetamide or N-methylformamide; the ether solvent is one of petroleum ether, isopropyl ether or diethyl ether.

[0053] Example 1: A method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material, comprising the following steps:

[0054] (1) Preparation of cyclodextrin-based macromolecular chain transfer agents:

[0055] In a 100 mL round-bottom flask equipped with a stirrer, heating bath, and gas protection device, 27 mL of N,N-dimethylformamide and 3.50 g of α-cyclodextrin were added. The mixture was heated to 50 °C under a nitrogen atmosphere and slowly stirred until completely dissolved. After the solution cooled to room temperature, 1.55 g of 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, 2.30 g of N,N-dicyclohexylcarbodiimide, and 0.38 g of 4-dimethylaminopyridine were weighed and added to the round-bottom flask. The flask was sealed and magnetically stirred at 30 °C for 21 h. Subsequently, the round-bottom flask was placed in a 10 °C water bath for 2 h to complete the reaction. The white precipitate was removed by vacuum filtration, and the bright yellow liquid was collected. The bright yellow liquid was added dropwise to 70 mL of petroleum ether to precipitate the product, and the precipitate was collected by vacuum filtration. Finally, it was dried in a vacuum oven at 45 °C until constant weight was obtained, yielding a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent.

[0056] pass 1 The prepared cyclodextrin-based macromolecular chain transfer agent was characterized by structural analysis using 1H NMR, such as... Figure 1 As shown in (1). Among them, 5.80 ~ 5.56 ppm belong to the -O group of cyclodextrin. H (-O) H , a), 4.81 ppm corresponds to the -OC of cyclodextrin H -O-(-OC H -C-, b), 4.45 ppm attributed to the -CH2-O of cyclodextrins H (-CH2-O) H (c); 3.74 ~ 3.41 ppm corresponds to the -OC of cyclodextrin. H -CH-O-(-OC H -CH-O-, d), -COO-C H 2-(-COO-C) H 2-, e) and RAFT chain transfer agent -SC H 2-(-SC H 2-, g). 3.33, 2.87 and 2.71, 2.50 ppm correspond to water, amide solvents and DMSO-d6, respectively. 1.68 ppm is attributed to the -S-CH2-C of the RAFT chain transfer agent. H 2-(-S-CH2-C) H2-, h), 1.53 ppm corresponds to the R1-CC of the RAFT chain transfer agent. H 3 (R1-CC) H 3, f); 1.25 ppm of CH3-(C) attributed to RAFT chain transfer agents H 2)9-(CH3-(C H 2) 9-,i). 0.84 ppm corresponds to the terminal -C of the RAFT chain transfer agent. H 3 (-C H 3, j). In summary, the chemical structures of both cyclodextrin and RAFT chain transfer agents are present, indicating that cyclodextrin-based macromolecular chain transfer agents have been successfully prepared.

[0057] (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material:

[0058] 60 mg of cyclodextrin-based macromolecular chain transfer agent, 310 mg of vanillin methacrylate, 2.50 mg of azobisisobutyronitrile (AIBN), and 1.30 g of N-methylformamide were added to a Schlenk tube, and the reaction substrate was mixed thoroughly with magnetic stirring. The sealed Schlenk tube was then immersed in liquid nitrogen. After the solvent was completely frozen, the stopcock was opened to create a vacuum for 3 minutes. The reaction flask was then closed, and the mixture was thawed until the solvent was completely melted. This process was repeated three times, with the last thaw cycle filled with an inert gas. The mixture was then placed in an oil bath at 65 °C and stirred for 16 h. After the reaction was complete, the reaction tube was immersed in liquid nitrogen to quench the reaction. After thawing, 60 mL of diethyl ether was added to the solution to precipitate the product, which was then collected by vacuum filtration. Finally, the washed precipitate was dried in a vacuum drying oven at 50 °C to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0059] The structure of the prepared cyclic cyclodextrin grafted with polyvanillin was characterized and analyzed, and its antibacterial properties were tested.

[0060] [Hydrogen nuclear magnetic resonance spectrum (NMR)] 1 [H NMR analysis]

[0061] pass 1 The chemical structure of the finger-shaped cyclodextrin grafted with polyvanillin was analyzed by ¹H NMR, and the results are as follows: Figure 1 (2) is shown. Among them, 9.84 ppm is attributed to the -C of the vanillin-derived monomer. H O(-C) H O, o), 7.47 and 7.28 ppm correspond to the benzene ring structure (-Ar-) of the vanillin-derived monomer. H , n). 5.80 ~ 5.56, 4.81 and 4.45 ppm are attributed to the -O group of cyclodextrin, respectively. H (-O) Ha) -OC H -O-(-OC H -O-, b) and -CH2-O H (-CH2-O) H c). 3.84 ppm corresponds to the Ar-OC of vanillin-derived monomers. H 3 (Ar-OC) H 3, m). 3.74 ~ 3.41 ppm attributable to cyclodextrins -OC H -CH-O-(-OC H -CH-O-,d), -COO-C H 2-(-COO-C) H 2-, e) and RAFT chain transfer agent -SC H 2-(-SC H 2-, g). 3.33, 2.87 and 2.71, 2.50 ppm correspond to water, amide solvents and DMSO-d6, respectively. 1.98 ppm is attributed to the -R2 (-R2, k) of the vanillin-derived monomer. The large peak of 1.70 ~ 1.10 ppm corresponds to the -S-CH2-C of the RAFT chain transfer agent. H 2-(-S-CH2-C) H 2-, h), R1-CC H 3 (R1-CC) H 3, f), CH3-(C H 2)9-(CH3-(C H 2) 9-, i) and homopolymer backbone R2-CC H 2-C (R2-CC) H 2-C, l). Additionally, 0.84 ppm was attributed to the terminal -C of the RAFT chain transfer agent. H 3 (-C H 3, j). In summary, the chemical structures of vanillin-derived monomers, cyclodextrins, and RAFT chain transfer agents are all present, and the C=C peak of the vanillin-derived monomers disappears after polymerization, indicating that cyclic cyclodextrin grafted onto polyvanillin has been successfully prepared.

[0062] FT-IR Infrared Spectroscopy Analysis

[0063] The characteristic absorption peaks of the finger-shaped cyclodextrin grafted with polyvanillin were analyzed by FT-IR, and the results are as follows: Figure 2 As shown. Among them, 3435 cm -1 Absorption peak attributable to the stretching vibration of OH in cyclodextrin; 2924 cm⁻¹ -1 The absorption peaks are attributed to the stretching vibrations of saturated CH4 atoms in the polymer backbone. (2850 and 2750 cm⁻¹)-1 The absorption peak corresponds to the stretching vibration of the CH group on the vanillin-derived monomer, at 1757 cm⁻¹. -1 The absorption peak attributable to the stretching vibration of the aldehyde carbonyl group (C=O) in the vanillin-derived monomer shifts from 1735 cm⁻¹ to 1757 cm⁻¹ after polymerization. -1 This further proves the successful preparation of cyclic cyclodextrin grafted with polyvanillin. 1697 cm -1 The absorption peak is attributed to the stretching vibration of the carbonyl group (C=O) of the vanillin-derived monomer ester, at 1463 cm⁻¹. -1 The absorption peak at 1270 cm⁻¹ is attributed to the stretching vibration of the C=C ring on the vanillin-derived monomer. -1 The absorption peaks at 1151 and 1032 cm⁻¹ correspond to the stretching vibrations of the vanillin-derived monomer Ar-OC. Meanwhile, the absorption peaks at 1151 and 1032 cm⁻¹ also correspond to these peaks. -1 The absorption peak at that point corresponds to the stretching vibration of the cyclodextrin COC. In summary, this further demonstrates the successful preparation of finger-shaped cyclodextrin grafted with polyvanillin.

[0064] [Macroscopic state and microscopic morphology]

[0065] The finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared by this invention is a white powder in its macroscopic state, such as... Figure 3 As shown in (1). This finger-shaped cyclodextrin-grafted polyvanillin antibacterial material can swell into a white emulsion in an aqueous medium, such as Figure 3 As shown in (2).

[0066] The microstructure of the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material prepared in this invention was tested by scanning electron microscopy (SEM) (e.g., Figure 4 SEM images show that the inner diameter of the cyclic cyclodextrin-grafted polyvanillin antibacterial material is between 100 and 300 nm, and the outer diameter is between 300 and 600 nm. The distance between the inner and outer diameters (ring width) is approximately 50 nm. Furthermore, obvious junctions are observed between the polymer rings, and these junctions exhibit increased roughness. 1 ¹H NMR (2) and FT-IR results show that the primary structure of the cyclic cyclodextrin-grafted polyvanillin antibacterial material is a linear homopolymer, which self-assembles into a secondary cyclic homopolymer through host-guest interactions in the organic phase. This is more conducive to the complete exposure of the active sites. The fully exposed active sites can fully bind to bacteria, thereby killing them.

[0067] [Antibacterial properties]

[0068] The antibacterial properties of cyclic cyclodextrin grafted with polyvanillin were evaluated using Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The results are as follows: Figure 5 As shown, a large number of bacteria were observed in the control groups containing *E. coli* and *Staphylococcus aureus*, while almost no bacteria were present in the sample groups containing *E. coli* + cyclic cyclodextrin-grafted polyvanillin and *Staphylococcus aureus* + cyclic cyclodextrin-grafted polyvanillin. Furthermore, the antibacterial rates of cyclic cyclodextrin-grafted polyvanillin against *E. coli* and *Staphylococcus aureus* reached 98.0% and 99.0%, respectively. Therefore, the cyclic cyclodextrin-grafted polyvanillin antibacterial material can effectively kill and inhibit bacterial growth. This is mainly because the cyclic topology of the homopolymer can fully expose the aldehyde groups and bind to the sulfhydryl groups on the bacterial surface, thereby causing bacterial cell membrane rupture and leading to bacterial death.

[0069] The prepared cyclic cyclodextrin grafted with polyvanillin achieved antibacterial rates of 98.0% and 99.0% against Escherichia coli and Staphylococcus aureus, respectively.

[0070] Example 2 A method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material, comprising the following steps:

[0071] (1) Preparation of cyclodextrin-based macromolecular chain transfer agents:

[0072] In a 100 mL round-bottom flask equipped with a stirrer, heating bath, and gas protection device, 36 mL of N,N-dimethylacetamide and 3.90 g of β-cyclodextrin were added. The mixture was heated to 55 °C under a nitrogen atmosphere and slowly stirred until completely dissolved. After the solution cooled to room temperature, 3.80 g of 4-cyano-4-[(dodecylthioalkylthiocarbonyl)thioalkyl]valeric acid, 3.70 g of N,N-diisopropylcarbodiimide, and 0.41 g of pyridine were weighed and added to the round-bottom flask. The flask was sealed and magnetically stirred at 40 °C for 29 h. The flask was then placed in a 15 °C water bath for 3 h to complete the reaction. The white precipitate was removed by vacuum filtration, and the bright yellow liquid was collected. The bright yellow liquid was added dropwise to 80 mL of isopropyl ether to precipitate the product, and the precipitate was collected by vacuum filtration. Finally, it was dried in a vacuum oven at 60 °C until constant weight was obtained, yielding a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent.

[0073] (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material:

[0074] 170 mg of cyclodextrin-based macromolecular chain transfer agent, 410 mg of vanillin acrylate, 3.10 mg of azobisisobutyronitrile, and 2.90 g of N,N-dimethylacetamide were added to a Schlenk tube, and the reaction substrate was mixed thoroughly with magnetic stirring. The sealed Schlenk tube was then immersed in liquid nitrogen. After the solvent was completely frozen, the stopcock was opened to create a vacuum for 6 min. The reaction flask was then closed, and the mixture was thawed until the solvent was completely thawed. This process was repeated four times, with the last thaw cycle filled with an inert gas. The mixture was then placed in an oil bath at 80 °C and stirred for 18 h. After the reaction was complete, the reaction tube was immersed in liquid nitrogen to quench the reaction. After thawing, 70 mL of isopropyl ether was added to the solution to precipitate the product, which was then collected by vacuum filtration. Finally, the washed precipitate was dried in a vacuum drying oven at 60 °C to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0075] The prepared cyclic cyclodextrin grafted with polyvanillin achieved antibacterial rates of 91.0% and 92.3% against Escherichia coli and Staphylococcus aureus, respectively.

[0076] Example 3 A method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material, comprising the following steps:

[0077] (1) Preparation of cyclodextrin-based macromolecular chain transfer agents:

[0078] In a 100 mL round-bottom flask equipped with a stirrer, heating bath, and gas protection device, 44 mL of N-methylformamide and 4.30 g of γ-cyclodextrin were added. Under a nitrogen atmosphere, the mixture was heated to 60 °C and slowly stirred until completely dissolved. After the solution cooled to room temperature, 5.20 g of 4-cyano-4-[(dodecylthioalkylthiocarbonyl)thioalkyl]valeric acid, 5.10 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and 0.54 g of pyridine were weighed and added to the round-bottom flask. The flask was sealed and magnetically stirred at 45 °C for 35 h. The flask was then placed in a 20 °C water bath for 4 h to complete the reaction. The white precipitate was removed by vacuum filtration, and the bright yellow liquid was collected. The bright yellow liquid was added dropwise to 90 mL of diethyl ether to precipitate the product, and the precipitate was collected by vacuum filtration. Drying in a vacuum oven at 70 °C until constant weight yields a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent.

[0079] (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material:

[0080] 240 mg of cyclodextrin-based macromolecular chain transfer agent, 480 mg of vanillin acrylate, 5.30 mg of dimethyl azobisisobutyrate, and 3.40 g of N,N-dimethylformamide were added to a Schlenk tube and magnetically stirred to ensure homogeneous mixing of the reaction substrate. The sealed Schlenk tube was then immersed in liquid nitrogen. After the solvent was completely frozen, the stopcock was opened to create a vacuum for 8 min. The reaction flask was then closed, and the mixture was thawed until the solvent was completely thawed. This process was repeated 5 times, with the last thaw cycle involving filling the system with an inert gas. The mixture was then placed in an oil bath at 85 °C and stirred for 20 h. After the reaction was complete, the reaction tube was immersed in liquid nitrogen to quench the reaction. After thawing, 80 mL of petroleum ether was added to the solution to precipitate the product, which was then collected by vacuum filtration. Finally, the washed precipitate was dried in a vacuum drying oven at 70 °C to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

[0081] The prepared cyclic cyclodextrin grafted with polyvanillin achieved antibacterial rates of 93.3% and 95.1% against Escherichia coli and Staphylococcus aureus, respectively.

Claims

1. A cyclic cyclodextrin-grafted polyvanillin antibacterial material, characterized in that: The antibacterial material has the following structure: Where: m is the number of structural units of the cyclodextrin, i.e., m=3, m=3.5 or m=4; R1 is -CN or -CH3; R2 is -H or -CH3; x is 0 or 2; n is the degree of grafting; y is the number of structural units of the vanillin-derived monomer; the product of y and n is the degree of polymerization.

2. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 1, comprising the following steps: (1) Preparation of cyclodextrin-based macromolecular chain transfer agents: In a container equipped with a stirring, heating bath, and gas protection device, an amide solvent and cyclodextrin are added. Under a nitrogen atmosphere, the mixture is heated to 45-65 °C and slowly stirred until completely dissolved. After the resulting solution has cooled to room temperature, a RAFT chain transfer agent, a carbodiimide condensing agent, and a pyridine catalyst are added sequentially. The mixture is then sealed and magnetically stirred at 20-50 °C for 20-36 h, followed by a water bath at -5-25 °C for 1-5 h to complete the reaction. After vacuum filtration, a bright yellow liquid is obtained. This bright yellow liquid is added dropwise to an ether solvent and then vacuum filtered to obtain precipitate A. Precipitate A is then vacuum dried at 40-75 °C to constant weight to obtain a yellow precipitate, which is the cyclodextrin-based macromolecular chain transfer agent. (2) Preparation of finger-shaped cyclodextrin-grafted polyvanillin antibacterial material: Cyclodextrin-based macromolecular chain transfer agent, vanillin-derived monomer, oil-soluble initiator, and amide solvent were added to a container and magnetically stirred to mix the reaction substrate evenly. Subsequently, the sealed container was immersed in liquid nitrogen and subjected to several freeze-thaw cycles, with the system filled with inert gas during the last cycle. Then, the reaction was stirred in an oil bath at 60-90 °C for 15-25 h. After the reaction was completed, the container was immersed in liquid nitrogen to quench the reaction. After thawing, an ether solvent was added to the solution to precipitate the product, which was then obtained by vacuum filtration. Precipitate B was dried under vacuum at 45-75 °C to constant weight to obtain the finger-shaped cyclodextrin-grafted polyvanillin antibacterial material.

3. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (1), the ratio of amide solvent to cyclodextrin is 25-50 mL: 3.10-4.60 g; the ratio of ether solvent to cyclodextrin is 60-120 mL: 3.10-4.60 g.

4. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (1), the RAFT chain transfer agent is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid or 4-cyano-4-[(dodecylthiocarbonylthiocarbonyl)thioalkyl]valerate, and the mass ratio of the RAFT chain transfer agent to cyclodextrin is 0.90~5.50 g: 3.10~4.60 g.

5. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (1), the carbodiimide condensing agent is one of N,N-diisopropylcarbodiimide, N,N-dicyclohexylcarbodiimide, or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and the mass ratio of the carbodiimide condensing agent to cyclodextrin is 2.00 ~ 5.50 g: 3.10 ~ 4.60 g.

6. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (1), the pyridine catalyst is pyridine or 4-dimethylaminopyridine, and the mass ratio of the pyridine catalyst to cyclodextrin is 0.35 ~ 0.55 g: 3.10 ~ 4.60 g.

7. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (2), the mass ratio of amide solvent to cyclodextrin-based macromolecular chain transfer agent is 1.00 ~ 3.50 g : 50 ~ 250 mg; the ratio of ether solvent to cyclodextrin-based macromolecular chain transfer agent is 50 ~ 110 mL : 50 ~ 250 mg.

8. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 3 or 7, characterized in that: The amide solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylformamide; the ether solvent is one of petroleum ether, isopropyl ether, or diethyl ether.

9. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (2), the vanillin-derived monomer is vanillin methacrylate or vanillin acrylate, and the mass ratio of the vanillin-derived monomer to the cyclodextrin-based macromolecular chain transfer agent is 200-500 mg: 50-250 mg.

10. The method for synthesizing a cyclic cyclodextrin-grafted polyvanillin antibacterial material as described in claim 2, characterized in that: In step (2), the oil-soluble initiator is one of azobisisobutyronitrile, azobisisoheptanenitrile, or dimethyl azobisisobutyrate, and the mass ratio of the oil-soluble initiator to the cyclodextrin-based macromolecular chain transfer agent is 0.67 ~ 6.70 mg: 50 ~ 250 mg.

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