Optimization of Critical Parameters for Carbodiimide Mediated Production of Highly Modified Chitosan

An optimization of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxy benzotriazole mediated conjugation of the polysaccharide chitosan with functional carboxylic acids was shown. Optimal parameters that enable resource-efficient synthesis of highly functionalized chitosan were identified. In particular, use of only catalytic instead of stoichiometric amounts of hydroxy benzotriazole and tight control of pH in reaction mixture resulted in highly efficient incorporation of the desired moieties as side chains in chitosan. As a result, the model reactant 4-azidobenzoic acid was incorporated resulting in a degree of substitution of over 30% with very high coupling efficacy of up to 90%. Similar results were obtained with other carboxylic acids such as methacrylic acid, 3-(2-furyl) propionic acid and 3-maleimido propionic acid, highlighting the broad applicability of our findings for the functionalization of chitosan.

Automated summary

The optimization of polysaccharide chitosan conjugation with functional carboxylic acids using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxy benzotriazole was demonstrated, showing resource-efficient synthesis of highly functionalized chitosan with optimal parameters. Catalytic amounts of hydroxy benzotriazole and tight pH control in the reaction mixture led to efficient incorporation of desired moieties as side chains in chitosan. Results showed high degree of substitution and coupling efficacy for various carboxylic acids, indicating broad applicability for chitosan functionalization.