Hidroliza peptida koji sadrže L-metionin i L-histidin pomoću različitih kompleksa paladijuma(II) i platine(II)

Studies of the palladium(II) and platinum(II) complexes have shown that they can be promising reagents for hydrolytic cleavage of peptides and proteins. These complexes bind to the heteroatom in the side chain of methionine or histidine and promote cleavage of the amide bond involving the carboxylic group of this anchoring amino acid. The consistent regioselectivity in the cleavage of histidine- and methionine-containing peptides promoted by palladium(II) and platinum(II) complexes and the mechanism of these hydrolytic reactions are not completely understood yet. A better knowledge of the coordination chemistry of histidine- and methionine-containing peptides with palladium(II) and platinum(II) complexes is necessary for understanding the regioselectivity of peptide and protein cleavage promoted by such complexes. In this thesis, the reactions of palladium(II) complexes, [Pd(dpa)Cl2] and [Pd(dpa)(H2O)2]2+ (dpa is 2,2’-dipyridylamine acting as a bidentate ligand) with the dipeptides methionylglycine (Met-Gly) and histidylglycine (His-Gly), and the N-acetylated derivatives of these dipeptides, MeCOMet-Gly and MeCOHis-Gly have been studied by 1H NMR spectroscopy. All reactions were carried out in the pH range 2.0-2.5 with equimolar amounts of the palladium(II) complex and the peptide at two different temperatures, 25 and 60 oC. In the reactions of [Pd(dpa)Cl2] and [Pd(dpa)(H2O)2]2+ with Met-Gly and His-Gly, no hydrolysis of the peptide bond was observed. The final product in these reactions was the [Pd(dpa)2]2+ complex. The square-planar structure of this complex was confirmed by X-ray analysis. The reaction of the [Pd(dpa)(H2O)2]2+ complex with the MeCOHis-Gly and MeCOMet-Gly peptides under the previously mentioned experimental conditions was remarkably selective in the cleavage of the amide bond involving the carboxylic group of methionine in the side chain. The modes of coordination of [Pd(dpa)Cl2] and [Pd(dpa)(H2O)2]2+ in the reactions with the nonacetylated peptides and the total steric inhibition of the hydrolytic reaction between [Pd(dpa)(H2O)2]2+ and MeCOHis-Gly can be attributed to the steric bulk of the palladium(II) complex. Furthermore, the 1H NMR spectroscopy was applied to study the reactions of [Pd(L)(H2O)2]2+ complexes (L is en, pic and dpa) with the N-acetylated tripeptides Lmethionylglycylglycine, MeCOMet-Gly-Gly, and glycyl-L-methionyl-glycine, MeCOGly-Met-Gly. All reactions were performed in the pH range 2.0-2.5 with equimolar amounts of t