Correlation between antimicrobial activity and chelating ability of 2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates

The chelating abilities of phosphobetaines [2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates; 1] for divalent cations (e.g., calcium ion, zinc ion, copper ion, and cadmium ion) were investigated to elucidate the correlation between the antimicrobial activity and the chelating ability. The maximal chelating ability was obtained with the compound having a dimethylene bridge as an intercharge distance between the phosphate and quaternary ammonium group; in contrast, the minimum was obtained with the compound with a trimethylene bridge. These behaviors paralleled the antimicrobial activity of these compounds. The antimicrobial activities, in terms of log (1/MIC) (minimum inhibitory concentration, mumol/L) of homologues of 1 against Candida albicans and Propionibacterium acnes were found to correlate linearly with the chelating ability for the calcium ion. This linear relationship is discussed with respect to the structure of the phosphobetaine moiety in the molecule of 1.