A novel method for obtaining a quaternary salt of chitosan

Abstract

A novel method for obtaining N,N,N-trimethylchitosan has been developed using dimethylsulfate as the methylant agent. Dimethylsulfate is not only more efficient but is less expensive than other commonly used agents. The resultant chitosan derivatives were characterized by FTIR, ¹H NMR, CP-MAS ¹³C NMR, and a capillary viscometer. Films were processed by casting and then hydrophilic changes were assessed by water contact angle measurements. The highest degree of substitution ($\overline{\mathit{DQ}}=52.5\%$) was obtained after a 6 h long-term reaction at room temperature. The use of higher temperatures helped to provoke polymeric thermal degradation and favor O-methylation over a N-methylation reaction.

Introduction

The intensive methylation of chitosan generates the N,N,N-trimethyl derivative (TMCh), characterized by possessing permanent positive charges in chains as a consequence of the quaternization of the amino groups in the C-2 position of the chitosan structure (Curti et al., 2003, Dung et al., 1994, Sieval et al., 1998). TMCh is a water-soluble polyelectrolyte with good intestinal absorption enhancing properties for hydrophilic and macromolecular drugs. It has been suggested as a soluble carrier for drug delivery (Kotzé et al., 1998, Thanou et al., 1998). Application of TMCh as an antibacterial agent has also been reported (Jia et al., 2001, Kim et al., 1997), with good activity described as the result of ionic interaction between chitosan positive charges and the negatively charged cell surface of bacteria.

TMCh can be synthesized by either covalent addition of a substituent containing a quaternary ammonium group, or by quaternization of the amino groups of the parent polymer (Curti et al., 2003). It is the latter method which has received most attention with alkylation agents such as alkyl halide usually employed. Degrees of quaternization ($\overline{\mathit{DQ}}$) superior to 53% have been achieved by reacting chitosan with iodomethane (an alkylation agent) in the presence of N-methyl-2-pyrrolidone (NMP). This process (Dung et al., 1994), has shown to be less severe than the usual quaternization reactions, this reducing the depolymerization intensity of the parent polymer. Despite being efficient, iodomethane is a highly volatile, carcinogenic and expensive reagent. In addition it offers limited control over a perilously chemical reaction.

In an attempt to overcome these disadvantages, an alternative sequence for the synthesis of chitosan quaternized derivatives is proposed using dimethylsulfate as the reactive agent. Dimethylsulfate is considerably less expensive than iodomethane and is less toxic. In addition it also has a high boiling point and no solvent is required for the reaction, unlike for NMP.