M. Hahn, M. Kleine, W. Sheldrick
Apr 28, 2001
Citations
1
Influential Citations
66
Citations
Quality indicators
Journal
JBIC Journal of Biological Inorganic Chemistry
Abstract
The pH- and time-dependent reaction of cis-[PtCl2(NH3)2] with the methionine- and histidine-containing peptides H-Gly-Met-OH, H-Gly-Gly-Met-OH, Ac-His-Gly-Met-OH, and Ac-His-(Ala)3-Met-OH at 313 K has been investigated by ion-pairing reverse phase HPLC and NMR spectroscopy. For equimolar solutions (c=0.8 mM, pH≈3 or 8.8), initial formation of the kinetically favored S-bound complex is followed by relatively rapid metallation of the neighboring methionine amide nitrogen NM to afford a κ2NM,S six-membered chelate. The strong trans effect of the methionine S then favors facile NH3 substitution, leading to generation of tridentate complexes such as [Pt(H-Gly-MetH–1-OH)-κ3NG,NM,S )(NH3)]+ or [Pt(H-Ac-His-GlyH–1-MetH–1-OH-κ3NG,NM,S)(NH3)]. In the case of H-Gly-Gly-Met-OH, this reaction is accompanied by loss of a second NH3 ligand in alkaline solution to generate the tetradentate κ4NG1,NG2,NM,S species. In contrast, cleavage of the backbone C(O)-N bond to the second metallated amide nitrogen after t>100 h is common to the tridentate complexes of the tri- and pentapeptides at pH<5. Although an imidazole-coordinated κ2N3H,S macrochelate is formed throughout the whole range 2.5≤pH≤10 for Ac-His-Gly-Met-OH, it slowly decays (t=10–1000 h) to the thermodynamically more stable tridentate κ3NG,NM,S complex. All major final products were separated and fully characterized by NMR and MS.