Chemical Modification of Oligo(Hexamethylene Guanidine): Synthesis of Alkylated Derivatives and Their Estimated Activity Against Mycobacterium Smegmatis

Abstract

It was found that oligo(hexamethylene guanidine) (OHMG) reacted very slowly with unactivated high-molecular-mass alkyl halides (dodecyl chloride), possibly due to steric hindrance and the low nucleophilicity of the guanidine moiety. Therefore, this alkyl halide could not be used to modify OHMG under conventional conditions. Ethylation of OHMG was much more facile. However, the substitution in the derivatives was broadly scattered (under ordinary conditions and reagent ratios). It was shown simultaneously that the antibacterial activity of the alkylated derivatives was less than that of the starting OHMG hydrochloride. Benzyl chloride reacted readily with OHMG to produce derivatives with the desired degree of substitution. It was found that benzyl derivatives with 0.2 degree of substitution were more active against mycobacteria than the starting hydrochloride with the activity gradually diminishing if the degree of substitution was increased further. The increased activity may have been related to the optimum increase of OHMG hydrophobicity and/or steric structure. The rather high antibacterial activities of the benzyl derivatives against Mycobacterium smegmatis strain ATCC 607 made them promising for further development and studies of the properties of alkylated OHMG derivatives to discover more active derivatives, including against M. smegmatis. The most obvious candidates could become the methylcarboxy-substituted OHMG derivatives.