Proton and metal ion interactions with glycylglycylhistamine, a serum albumin mimicking pseudopeptide

The macro- and microprotonations of glycylglycylhistamine (GGHA) have been determined by combined potentiometric and H-1-NMR methods. The complexation of GGHA with Co(II), Ni(II), and Cu(II) has been studied by potentiometric, EPR, and H-1-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-N-3 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 N-1-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). 3H(2)O verified the expected four nitrogen coordination in the equatorial plane of Cu(II).