title: 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.
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland; West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
authors: V
authors: V
authors: Patrulea
authors: University Hospital of Lausanne (CHUV-UNIL), Department of Musculoskeletal Medicine, EPCR/02/ch. Croisettes 22, 1066 Epalinges, Switzerland.
authors: Lee Ann
authors: LA
authors: Applegate
authors: West University of Timisoara, Department of Biology-Chemistry, Pestalozzi 16, Timisoara 300115, Romania; West University of Timisoara, Advanced Environmental Research Laboratories, Oituz 4, Timisoara 300086, Romania.
authors: V
authors: V
authors: Ostafe
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland.
authors: O
authors: O
authors: Jordan
authors: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.
authors: G
authors: G
authors: Borchard
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008745:Methylation; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: C546859:6-O-carboxymethyl-N,N,N-trimethyl chitosan; D014867:Water; D048271:Chitosan
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