pH regulation of calcium recognition by an amino acid containing acyclic ionophore

Calcium ion recognition by a dicarboxylic ionophore containing two (S)-phenylalanine residues joined via an amide bond by a flexible tri-oxa-undecanoyl bridge (Phe-3-O) has been investigated in a wide pH range (from pH 2 to 12). Experiments were performed in methanol and chloroform by 1H and 13C NMR, relaxation times and 2D NMR (COSY, NOESY and J-resolved experiments). Recognition is shown to be regulated by pH, as it occurs in at least three different coordination modes according to the experimental conditions. Even at low pH (pH 2) the ion is already complexed in the compartment created by the ethereal oxygens and the amide carbonyls. At higher pH, it becomes fully encapsulated in a pseudo-cyclic structure and at very basic pH it is localized between the amide carbonyls and the carboxylates. For these peculiar properties Phe-3-O appears to be a very promising ionophore in a trans-membrane pH gradient system.