Synthesis and antibacterial analysis of C-6 amino-functionalised chitosan derivatives

Abstract

Synthesis of 6-O-(3-alkylamino-2-hydroxypropyl) derivatives of chitosan was achieved using a four-step strategy of N-protection, O-epoxide addition, epoxide ring opening using an amine and N-deprotection. Benzaldehyde and phthalic anhydride were used for the N-protection step, producing N-benzylidene and N-phthaloyl protected derivatives, respectively, resulting in two corresponding final 6-O-(3-alkylamino-2-hydroxypropyl) derivative series, BD1-BD6 and PD1-PD14. All the compounds were characterized using FTIR, XPS and PXRD studies and tested for antibacterial efficacy. The phthalimide protection strategy was found to be easier to apply and effective in terms of the synthetic process and improvement in antibacterial activity. Amongst the newly synthesized compounds, PD13 (6-O-(3-(2-(N,N-dimethylamino)ethylamino)-2-hydroxypropyl)chitosan) was the most active with eight times greater activity compared to the unmodified chitosan and, PD7 6-O-(3-(3-(N-(3-aminopropyl)propane-1,3-diamino)propylamino)-2-hydroxypropyl)chitosan) having a four-fold activity than chitosan, was found to be the second most potent derivative. This work has produced new chitosan derivatives those are more potent than chitosan itself and show promise in antimicrobial applications.