Preparation Of Chitosan Derivatives Based On "Click" Reaction And Their Bioactivities

Chitosan,as one of the most abundant renewable resources,is the only cationic aminopolysaccharide in nature.The increasing interest in chitosan-based biomaterials is due to its admirable characteristics such as good biodegradable,biocompatible,and a degree of bioactivity.However,the industrial applications of chitosan are considerably limited by poor solubility in both organic and aqueous solvents and weak bioactivity,such as antifungal and antioxidant properties.Chemical structural modification is the powerful method to improve the solubility and bioactivity as well as achieve high-value utilization of chitosan,and it is likely to be high-efficiency to introduce the heterocycle groups into chitosan backbones.Of all the reactions of the synthesis of heterocycle compounds,Click reaction is a near-perfect effective reaction.Unfortunately,three are many burning questions about the unsystematic research on the chemical modification of chitosan based on Click reaction and the lack of study on improving the solubility and enhancing the bioactivity of chitosan derivatives,urgently needed to be addressed.In this study,sixteen kinds of chitosan derivatives with 1,2,3-triazole groups and five kinds of chitosan derivatives bearing 1,2,3-triazolium moieties were synthesized by the introduction of some active groups,such as hydroxyl,amino,acylhydrazine,nitrogenous cations,and quaternary phosphonium salts,to chitosan backbones using two different preparation routes based on Click reaction.And the detailed chemical structures of these chitosan derivatives were characterized by means of FTIR,~1H NMR,as well as elemental analysis and the degrees of substitution and water solubility of them were also also measured.The antifungal activities against Botrytis cinerea Pers.,Fusarium oxysporum f.sp.niveum,Phomopsis asparagi(Sacc.)Bubak,and Fusarium oxysporum f.sp.cucumerium and the antioxidant properties of chitosan derivatives were evaluated to explore the influence of chain length,functional groups,and methylation on bioactivities and to screen the chitosan derivatives with relatively stronger antifungal and antioxidant properties.Firstly,1,2,3-triazole-functionalizedchitosanderivativescontaining hydroxyalkyl with different chain,amino,and acylhydrazine groups were synthesized by N-phthaloylation,bromination,azidation,Click reaction,and hydrazinolysis reaction.The antifungal results showed that the chain length had unnoticeable influence on antifungal activities of 1,2,3-triazole-functionalized chitosan derivatives containing hydroxyalkyl groups and amino-functionalized chitosan derivative bearing1,2,3-triazole exhibited the strongest antifungal activity compared with others.The antioxidant results demonstrated that all synthesized chitosan derivatives bearing1,2,3-triazole moieties exhibited enhanced greatly antioxidant properties compared with chitosan,especially at least 90 percent of superoxide radicals could be scavenged by them at the minimum test concentration.Besides,negligible impact of chain length on antioxidant properties of 1,2,3-triazole-functionalized chitosan derivatives containing hydroxyalkyl groups was observed and it was found that amino and acylhydrazine-functionalized chitosan derivatives bearing 1,2,3-triazole exhibited the stronger antioxidant activity.But the poor water-solubility of the synthesized chitosan derivatives could still be a great trouble.In order to improve the water-solubility,1,2,3-triazole-functionalized chitosan derivatives with good water-soluble containing different-chain trialkylammonium bromide,methylimidazolium bromide,methylmorpholinium bromide,and methylpiperidinium bromide were synthesized by the introduction of nitrogenous cations to chitosan backbones using Click reaction.The results indicated that all synthesized nitrogenous cations functionalized chitosan derivatives bearing1,2,3-triazole moieties exhibited improved water solubility,especially at alkaline pH.The antifungal results showed that all synthesized nitrogenous cations functionalized chitosan derivatives bearing 1,2,3-triazole moieties displayed superduper antifungal activities and trimethylammonium-functionalized chitosan derivatives bearing1,2,3-triazole exhibited the strongest antifungal activity against the tested plant threatening fungi with the inhibitory indices of 80%above at 1.0 mg/m L.Moreover,antifungal activity profiles were dependent on the variation in alkyl chain length and increasing the length of the alkyl chain on the trialkylammonium salts resulted in a decrease in antifungal activity of chitosan derivatives against four plant-threatening fungi.It was found from the antioxidant results that all synthesized nitrogenous cations functionalized chitosan derivatives bearing 1,2,3-triazole moieties exhibited remarkable improved antioxidant activities over chitosan and among them methylimidazolium-functionalized derivative exhibited the strongest capacity for scavenging free radicals and reducing power.In addition,the antioxidant property of1,2,3-triazole-functionalized chitosan derivatives containing trialkylammonium salts seemed to make no difference with the variation in alkyl chain length.Tofurtherenhancetheantifungalandantioxidantactivities,1,2,3-triazolium-functionalized chitosan derivatives containing trimethylammonium bromide and methylimidazolium bromide were obtained for the first time by methylation of 1,2,3-triazole moieties.The antifungal and antioxidant assessments revealed that the methylation could play a facilitating role on antifungal and antioxidant properties of chitosan derivatives bearing 1,2,3-triazole groups.In order to simplify the reaction steps,novel chitosan derivatives bearing1,2,3-triazolemoietieswerepreparedbyintroducingthepyridine,trimethylammonium salts,triphenylphosphonium salts to chitosan backbones using quaternization,propargylation,Click reaction and subsequently followed by methylation with iodomethane to synthesize novel chitosan derivatives bearing1,2,3-triazolium moieties.While all novel chitosan derivatives bearing 1,2,3-triazole showed enhanced antifungal activity at the tested concentrations compared with chitosan,chitosan derivatives bearing trimethylammonium and triphenylphosphonium salts exhibited the strongest.Meanwhile,the antioxidant property of novel chitosan derivatives exhibited remarkable improvement over chitosan.Moreover,it demonstrated again that methylation could facilitate the antifungal and antioxidant activity of chitosan derivatives bearing 1,2,3-triazole moieties.In this study,synthesis,characterization,antifungal and antioxidant activities of chitosan derivatives based on Click reaction were studied systematically,and water-soluble chitosan derivatives bearing 1,2,3-triazole and 1,2,3-triazolium moieties with greatly enhanced bioactivities were screened via antifungal and antioxidant assays.This work provides theory basis for further exploitation and utilization of high-valued chitosan derivatives based on Click reaction and also offers the new ideas to the design and development of chitosan-based new materials and medicines.