Optimized synthesis of O-carboxymethyl-N,N,N-trimethyl chitosan

Abstract

We present here the synthesis of a highly O-carboxymethylated chitosan derivative. First, an improved protocol for the two-step synthesis of N-trimethyl chitosan (TMC) from chitosan was developed, yielding a maximum degree of quaternization (DQ) of up to 46.6%. Successively, the chitosan derivative O-carboxymethyl-N-trimethyl chitosan (CMTMC) was synthesized from the TMC obtained by applying an optimized synthesis pathway. In contrast to previous reports, the optimized protocol was shown to yield very high rates (>85%) of O-carboxymethylation of CMTMC, as shown by (1)H NMR and heteronuclear single quantum correlation ((1)H-(13)C HSQC). Finally, in vitro cytocompatibility (viability >80%) of the polymer was demonstrated using human fibroblasts.

Keywords: Chitosan; Chitosan (PubChem CID: 21896651); Chitosan derivatives; Chloroacetic acid (PubChem CID: 300); Drug/gene delivery; Formaldehyde (PubChem CID: 712); Formic acid (PubChem CID: 284); Isopropanol (PubChem CID: 3776); Methyl iodide (PubChem CID: 6328); Methylation; Quaternization.