ZnII complex with a phenanthroline-containing macrocycle as receptor for amino acids and dipeptides -: Hydrolysis of an activated peptide bond

The interaction between several L-amino acids and dipeptides and the Zn-II complex with ligand L, a macrocycle containing a triamine chain linking the 2,9 positions of a phenanthrohne moiety, has been studied by means of potentiometric and H-1 NMR spectroscopic measurements in aqueous solutions. In the [ZnL](2+) complex, the metal ion displays an unsaturated coordination environment and the metal can act as a binding site for these substrates. Amino acids and dipeptides in their neutral (zwitterionic) form bind to Zn-II through the carboxylate function and, when in their anionic form, through the amine group. In this case the carbonyl of the amide function is probably also involved in metal coordination. Amino acids containing aromatic pendants form the most stable complexes, due to hydrophobic and/or Ti-stacking interactions between the aromatic subunits of the substrates and the phenanthroline moiety of the metal receptor. The hydrolytic properties of the Zn-II complex with L, involving the cleavage of the peptide bond, have been tested by using L-leucine-p-nitroanilide (LNA), which contains an activated peptide bond. This substrate forms stable [ZnL(LNA)](2+) and [ZnL(OH)(LNA)](+) complexes. The formation of the [ZnL(OH)(LNA)](+) complex is followed by LNA hydrolysis, through a nucleophilic attack of the Zn-OH function on the peptide bond. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.