Synthesis and Antibacterial Assessment of Water-Soluble Hydrophobic Chitosan Derivatives Bearing Quaternary Ammonium Functionality
Chitosan is a naturally occurring, bio-degradable, non-toxic, non-allergenic bio-polysaccharide derived from chitin, found in abundance in nature. Studies aimed at deriving newer applications of chitosan are hence of interest. Among these, one of the focuses of investigations is aimed at excellent antimicrobial activity demonstrated by chitosan. In this context, certain quaternary ammonium derivatives of chitosan have been shown in the past to be highly effective antibacterial materials. In the present study, substituted chitosan derivatives were synthesized and further quaternized using Quat-188 to produce water soluble derivatives at neutral pH. The antibacterial assessments of the quaternized derivatives of substituted chitosan were performed on liquid cultures of E. coli and S. aureus and results expressed in terms of Minimum Inhibitory Concentration (MIC). A comparison with the activity exhibited by the unsubstituted chitosan quaternized derivative indicated that hydrophobic substituents greatly enhance the activity. Three synthetic routes, viz. Bosch reduction, gamma-lactone addition and an anhydride addition were used to obtain hydrophobic as well as strongly and weakly acidic organic groups. In the case of Bosch reduction using aromatic aldehydes, a logarithmic relationship was observed between the %substitutions targeted and %substitutions obtained. n-Octyl aldehyde showed linear correlation between targeted and obtained %substitutions only in the presence of dimethyl formamide. gamma-Octanoic lactone addition resulted in very low levels of substitution (<1.5% with up to 30% feed). However, the derivatives obtained using this method provided excellent antibacterial activity (MIC=16microgm/mL, compared to 128microgm/mL for the unsubstituted quaternized chitosan). Heptanoic anhydride produced materials with 1.5-2.4% substitution which demonstrated high antibacterial activity (MIC=32microgm/mL); however no substitution control could be realized using anhydride route. gamma-Lactone addition and anhydride addition are simple methods of synthesizing chitosan derivatives with potential applications in industry. Chitosan derived gels were prepared using an aromatic, rigid (terephthaldicarboxaldehyde) and an aliphatic, flexible (glutaraldehyde) cross-linkers and their quaternized derivatives exhibited antibacterial activity at low levels of cross-linking. Additionally, gels with rigid cross-linker exhibited enhanced activity compared to the flexible cross-linker. The onset of gelation for the aromatic gels was found to vary with the extent of the presence of cross-linker in gels (4.5mg/mL for 4.8% and 3.0mg/mL for 49%).
Advisor:Ioan Negulescu; Frederick A. Rainey; William H. Daly; Gudrun Schmidt; Graca Vicente
School:Louisiana State University in Shreveport
School Location:USA - Louisiana
Source Type:Master's Thesis
Date of Publication:11/17/2004