Relation between structure and antimicrobial activity of 2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates

A series of phosphobetaines [2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates], having different alkyl chains and a methylene bridge separating the phosphate and ammonio group, was investigated in order to provide a new antimicrobial agent. Maximal activity was obtained with the compound having a hexadecyl group as a long-chained alkyl group, two methyl groups as short-chained alkyl groups, and a dimethylene bridge as an intercharge distance. In contrast, sodium 2-(N-hexadecyl-N-methylamino)ethyl hydrogen phosphate, 2-(N-hexadecyl-N,N-dimethylammonio)-1-hydroxyethyl iodide, and N-octadecyl-N,N-dimethylammonio acetate showed decreased activity, indicating that the presence of a phosphobetaine moiety was essential for activity. Thus, 2-(N-hexadecyl-N,N-dimethylammonio)ethyl hydrogen phosphate has been found to possess strong antimicrobial activity and a broad antimicrobial spectrum against nine kinds of bacteria (e.g., fungi, yeast, gram-negative and gram-positive bacteria), which are comparable with those of chlorhexidine digluconate.