Disparate behavior of pyrazine and pyridazine platinum(II) dimers in the hydrolysis of histidine- and methionine-containing peptides and unique crystal structure of {[Pt(en)Cl]<inf>2</inf>(μ-pydz)}Cl<inf>2</inf> with a pair of NH⋯Cl^-⋯HN hydrogen bonds supporting the pyridazine bridge

Abstract

Treatment of [Pt(en)Cl2] complex with pyridazine lead to the formation of new diplatinum(II) coordination compound {[Pt(en)Cl] 2(μ-pydz)}Cl2, which was characterized by NMR spectroscopy and single-crystal X-ray diffraction. X-ray analysis revealed that the needed support for the pyridazine bridge formation, which in other metal complexes has been mostly provided by additional bridging units coordinated to metal centers, might come from supramolecular interactions such as intermolecular hydrogen bonds. This complex was converted into the corresponding aqua complex, {[Pt(en)(H2O)]2(μ-pydz)}4+, and 1H NMR spectroscopy was applied for comparison of its catalytic activity with that of the analogous pyrazine-bridged {[Pt(en)(H 2O)]2(μ-pz)}4+ complex in the hydrolysis of the N-acetylated l-histidylglycine (Ac-l-His-Gly) and l-methionyl-glycyl-l- histidyl-glycineamide (Ac-l-Met-Gly-l-His-GlyNH2). All reactions were performed in the pH range 2.0-2.5 and at 37 C. It was found that although dimerization, in general, improves significantly the hydrolytic potency of Pt(II) complexes, the pyridazine Pt(II) dimer is significantly less active than its pyrazine Pt(II) analog, which is probably due to an increased steric effect exerted in the former complex by the ortho-position of the two nitrogen atoms. Consequently, {[Pt(en)(H2O)]2(μ-pydz)}4+ only binds to the methionine sulfur atom of the Ac-l-Met-Gly-l-His-GlyNH 2 peptide and promotes cleavage of amide bond that involves the carboxylic group of methionine. In contrast, the analogous pyrazine Pt(II) dimer reacts with both methionine and histidine residues of this tetrapeptide, promoting cleavage of amide bonds involving carboxylic groups of both of these anchoring amino acids. Considering these results it can be assumed that in the polypeptide containing both methionine and histidine residues the regioselective cleavage of the amide bond involving only the carboxylic group of methionine can be achieved successfully by using the presently investigated pyridazine-bridged Pt(II) complex.