A novel method for obtaining a quaternary salt of chitosan
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 () 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.
Section snippets
Experimental
The starting chitosan was purchased from Polymar (CE, Brazil) and was used “as supplied”. Dimethylsulfate was obtained from Vetec (R. Janeiro, Brazil) and other solvents used were supplied by Synth (S. Paulo, Brazil).
Five methylation reactions with varying time and temperature were carried out for comparison. Samples were identified as T when heated at 70 °C or R for room temperature, followed by the reaction time, in which ‘H’ indicates hours and ‘M’ minutes. The basic reaction sequence
Results and discussion
The average degree of acetylation, , and the average degree of substitution (or quaternization), , are the most important characteristics of chitosan and its derivatives. A variety of techniques are available to determine both, however NMR spectroscopy is considered to yield the most reliable results. The 1H NMR spectrum of chitosan (Fig. 1) indicated the following characteristic signals (Britto & Campana-Filho, 2004): (a) δ = 4.5 < δ < 5.0 attributed to hydrogen bonded to the anomeric carbon
Conclusions
The use of dimethylsulfate as a methylant agent for synthesizing N,N,N-trimethylchitosan has been demonstrated as a simple and an effective alternative to more expensive and often more toxic agents . The quaternization intensity was found to be time and temperature dependent, with final degrees varying from 15.8% to 52.5%. NMR and FTIR spectroscopy was used to describe the main alterations occurring in the starting chitosan, where undesirable O-methylation was observed to take place for
Acknowledgments
The authors wish to thank Dr. Sergio P. Campana Filho for the viscometric measurements in his laboratory at Instituto de Química de São Carlos, USP. This work was supported by CNPq and Embrapa.
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