ic0506613_si_001.pdf (245.68 kB)
Thioether Complexes of Palladium(II) and Platinum(II) as Artificial Peptidases. Residue-Selective Peptide Cleavage by a Palladium(II) Complex
journal contribution
posted on 2005-11-28, 00:00 authored by Stacey A. Stoffregen, Amanda K. K. Griffin, Nenad M. KostićWe report the synthesis and characterization of perchlorate salts containing the following three novel complex
cations each with a bidentate thioether ligand: binuclear cis-[Pt(CH3SCH2CH2CH2SCH3)(μ-OH)]22+, mononuclear
cis-[Pt(CH3SCH2CH2CH2SCH3)(H2O)2]2+, and mononuclear cis-[Pd(CH3SCH2CH2CH2SCH3)(H2O)2]2+. Despite their
analogous compositions, the mononuclear Pt(II) and Pd(II) complexes differ in the selectivity with which they promote
the hydrolysis of polypeptides. The complex cis-[Pt(CH3SCH2CH2CH2SCH3)(H2O)2]2+ promotes slow but selective
cleavage of Met−Pro peptide bonds at pH 2.0. The selectivity of the complex cis-[Pd(CH3SCH2CH2CH2SCH3)(H2O)2]2+ is pH-dependent. At pH 2.0, this Pd(II) complex promotes residue-selective hydrolysis of the X−Y bond
in X-Y-Met and X-Y-His sequences; the rate is enhanced when residue Y is proline. At pH 7.0, this kinetic preference
becomes sequence-selective in that the Pd(II) complex exclusively cleaves the X−Pro bond in X-Pro-Met and
X-Pro-His sequences. The enhanced reactivity of the X−Pro amide group is attributed to the high basicity of its
carbonyl oxygen atom. Binding of the metal(II) atom enhances the electrophilicity of the carbonyl carbon atom and
promotes nucleophilic attack by a solvent water molecule. The bidentate thioether ligand disfavors the formation of
hydrolytically unreactive complexes, allowing the Pd(II) complex to promote the cleavage reaction.