| Chitosan(CS)is a positive charged alkaline polysaccharide which exists in large quantities in nature.CS diaplays good application prospects in food,cosmetics,biomedicine and bioengineering fields in virtue of its good antibacterial activity,biocompatibility and biodegradability.However,CS is insoluble in neutral/alkaline aqueous solutions and most organic solutions except for some acidic solutions because of the extensive existence of intramolecular and intermolecular hydrogen bonds and high degree of crystallinity,which cannot meet the requirements of neutral/alkaline environments or physiological environments and greatly limits its range of applications.Therefore,the preparation of CS derivatives with enhanced water-soluble and antibacterial activity with low toxicity has become an urgent problem to be solved in the process of CS development,which has important scientific significance and socio-economic values.In this thesis,four reactive antibacterial agents were designed and synthesized.The bromooctane/bromodecane/bromododecane,N,N-dimethyl ethanolamine(DMEA),and isocyanone diisocyanate(IPDI)were adopted to prepare three new isocyanate terminated quaternary ammonium salts with different chain lengths(NCO-Cn-QAS,n=8,10,12).Besides,NCO-Betaine was prepared from 1,3-propionic lactone(1,3-PS),DMEA and IPDI.The antimicrobial agents can be bonded to CS skeleton via proper chemical reactions between-NCO and C2-NH2 and C6-OH groups,and then quaternary ammonium CS derivatives(N-QCS and O-QCS)and quaternary ammonium salt / zwitterionic CS derivatives(N-QBCS and O-C10-QBCS)were obtained.The structure and crystallinity of the products were charactered by Fourier transform infrared spectroscopy(FTIR),nuclear magnetic resonance(1H-NMR),and X-ray diffraction spectra(XRD),and the solubility,charge,antibacterial activity,and cytotoxicity properties were tested through ultraviolet-visible spectrophotometry(UV-vis),Zetasizer potentiometer,full automatic growth curve analyzer,and Microplate Reader.The solubility experiments show that the CS derivatives obtained enhanced solubility in some degree and the soluble p H range under medium and alkaline conditions were expanded when compared with CS.Meanwhile,the solubility increases with the degree of substitution.The antimicrobial activity of the CS derivatives against E.coli and S.aureus was studied to obtain the minimal inhibitory concentration(MIC),and the antimicrobial kinetics against were simultaneously studied.The results indicated that the antimicrobial activity of the quaternary ammonium chitosan against E.coli and S.aureus increase to some extent compared with that of CS,and its antibacterial activity against S.aureus was superior to that against E.coli.Within a certain range,the antimicrobial activity of the CS derivatives increased with the increasing of the degree of substitution of quaternary ammonium salt,while the antimicrobial activity showed a slight decline when the degree of substitution increased further.Among NQCS systems,the N-C12-QCS showed better antimicrobial activity with MIC 400 ?g/m L for E.coli and 80 ?g/m L for S.aureus,and O-C10-QCS showed better antimicrobial activity in OQCS systems,with MIC 250 ?g/m L for E.coli and 120 ?g/m L for S.aureus.The antimicrobial kinetics studies revealed that the early bacteriostatic duration was prolonged with the increasing of quaternized ammonium salt substitution and concentration.After the introduction of NCOBetaine,the N-QBCS system still had good antibacterial activity,while the antibacterial activity of O-C10-QBCS system were significantly reduced,indicating that the antibacterial activity of the double-modified derivatives could be regulated by introducing zwitterions.Cytotoxicity experiments showed that quaternized CS derivatives displayed different cytotoxicity,while the zwitterion could greatly reduce the cytotoxicity of quaternized CS and improve the biocompatibility of the double-modified CS derivatives. |
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