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 1 H-NMR methods. The complexation of GGHA with Co(II), Ni(II), and Cu(II) has been studied by potentiometric, EPR, and 1 H-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).