Proton and Metal Ion Interactions with Glycylglycylhistamine, a Serum Albumin Mimicking Pseudopeptide

Abstract

The macro- and microprotonations of glycylglycylhistamine (GGHA) have been determined by combined potentiometric and 1H-NMR methods. The complexation of GGHA with Co(II), Ni(II), and Cu(II) has been studied by potentiometric, EPR, and 1H-NMR methods. In the pH range 3−11.2, more or less deprotonated monomeric complexes (MLH, ML, MLH-1, MLH-2, MLH-3) formed in all systems. In the case of Ni(II) and Cu(II) at physiological pH, the MLH-2 species is predominant with four nitrogen coordination sites (one amino, two peptide, and one imidazole-N3 nitrogens) in square planar arrangement. In Co(II) containing systems however, CoL is the predominant complex near pH 7 with a macrochelate coordination of terminal amino and imidazole nitrogens, while CoLH-2 species forms at much higher pH. In accordance with NMR measurements, the formation of MLH-3 species can be assigned to the further deprotonation of the N1-pyrrolic nitrogen in the imidazole ring without metal coordination. The formation constants determined were compared with those of the analogous histidine derivatives. Single-crystal X-ray analysis of CuLH-2·3H2O verified the expected four nitrogen coordination in the equatorial plane of Cu(II).