Reactions of the cis-diamminediaquaplatinum(II) cation with histidine and related molecules

The reaction of cis-[Pt(NH3)(2)(H2O)(2)](2+) (1) with histidine (H(3)his(+)) at pH 2-3 gave initially complexes with histidine bound through carboxylate only, then, after standing, the complex containing an amine nitrogen (N-A), carboxylate oxygen-chelate ring, [Pt(NH3)(2)(H(2)his-N-A,O)](2+). Increasing the pH to 8-9 caused loss of one imidazole proton, followed by isomerization to the species with a imidazole N(3), N-A-chelate ring, [Pt(NH3)(2)(Hhis-N-A,N(3))](+). From the variation of NMR parameters with pH, pK(a) for loss of the last imidazole proton was determined (11.2+/-0.1). Histidine methyl ester and histidinamide each reacted slowly with 1 at pH 5.5 to give the N-A,N(3)-chelate complex. With N-(histidyl)glycine the initial complexes at pH 5 contained the ligand bound only through carboxylate, but a N-A,N(3)-chelate complex then formed. With an excess of 1, a second diammineplatinum moiety was bound, initially through the free carboxylate, then chelated by carboxylate and peptide nitrogen. With N-acetylhistidine and N-beta-alanyl)histidine at pH 4-5, the initial complexes also contained carboxylate-bound ligands, then a chelate ring was formed involving carboxylate and the deprotonated amide or peptide nitrogen, N-A. With N-(glycyl)histidine, more complex reactions involving the terminal nitrogen atom also occurred. In alkaline solution, these N-A,O-chelate complexes reacted slowly to form a dinuclear complex with one ligand bound to one Pt atom through N-A and N(3), and to the second platinum through N(1) of bridging imidazolate. The second ligand was bound monodentate to the second platinum through N-A.