Synthesis of guanidinylated chitosan with the aid of multiple protecting groups and investigation of antibacterial activity

• Published in: Carbohydrate polymers Vol. 127; pp. 407 - 417
• Main Authors: Sahariah, Priyanka, Óskarsson, Bjarni M., Hjálmarsdóttir, Martha Á., Másson, Már
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 20.08.2015
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Chitosan - analogs & derivatives; Chitosan - chemical synthesis; Chitosan - chemistry; Chitosan - pharmacology; Escherichia coli - drug effects; Guanidine - chemistry; Guanidinyl chitosan; Microbial Sensitivity Tests; Molecular Structure; Molecular Weight; Quaternary ammoniumyl chitosan; Silyl chitosan; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Structure–activity relationship (SAR); Trimethyl chitosan (TMC); Trimethyl chitosan (TMC); Antibacterial activity; Structure–activity relationship (SAR); Silyl chitosan; Guanidinyl chitosan; Quaternary ammoniumyl chitosan
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.03.061

•Guanidinylated chitosan derivatives were synthesized utilizing two different protecting groups.•Reactions in organic medium enabled quantitative conversion.•100% N-modification and good control of the degree of substitution was achieved.•The derivatives were well characterized using 1H and COSY NMR and IR spectroscopy.•Structure–activity relationship was developed against S. aureus and E. coli. A new synthetic approach employing two types of protecting groups, tertiarybutyldimethylsilyl (TBDMS) and tertiarybutyloxycarbonyl (Boc) was developed to obtain a series of guanidinylated chitosan derivatives. The synthesis was carried out in organic solvents which allowed quantitative reaction, a good control on the degree of substitution, and 100% substitution of the chitosan amino groups. Similar derivatives carrying the trimethylammonium group were also synthesized as reference compounds. All the derivatives were characterized using 1H and COSY NMR and IR spectroscopy. The antibacterial effect against clinically relevant strains of S. aureus and E. coli was found to increase with increase in the degree of substitution and decrease in the spacer length of the derivatives in both the series. An optimum activity could be obtained at a degree of substitution above 0.5 for most derivatives. The trimethylammonium derivatives showed slightly higher activity than the corresponding guanidinium derivatives but a similar structure–activity relationship was obtained.