Thioether Complexes of Palladium(II) and Platinum(II) as Artificial Peptidases. Residue-Selective Peptide Cleavage by a Palladium(II) Complex Stacey A. Stoffregen Amanda K. K. Griffin Nenad M. Kostić 10.1021/ic0506613.s001 https://acs.figshare.com/articles/journal_contribution/Thioether_Complexes_of_Palladium_II_and_Platinum_II_as_Artificial_Peptidases_Residue_Selective_Peptide_Cleavage_by_a_Palladium_II_Complex/3254593 We report the synthesis and characterization of perchlorate salts containing the following three novel complex cations each with a bidentate thioether ligand:  binuclear <i>cis</i>-[Pt(CH<sub>3</sub>SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>)(μ-OH)]<sub>2</sub><sup>2+</sup>, mononuclear <i>cis</i>-[Pt(CH<sub>3</sub>SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>)(H<sub>2</sub>O)<sub>2</sub>]<sup>2+</sup>, and mononuclear <i>cis</i>-[Pd(CH<sub>3</sub>SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>)(H<sub>2</sub>O)<sub>2</sub>]<sup>2+</sup>. 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 <i>cis</i>-[Pt(CH<sub>3</sub>SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>)(H<sub>2</sub>O)<sub>2</sub>]<sup>2+</sup> promotes slow but selective cleavage of Met−Pro peptide bonds at pH 2.0. The selectivity of the complex <i>cis</i>-[Pd(CH<sub>3</sub>SCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>)(H<sub>2</sub>O)<sub>2</sub>]<sup>2+</sup> 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. 2005-11-28 00:00:00 nucleophilic attack hydrolytically unreactive complexes cleavage reaction pH 2.0. OH Pt perchlorate salts Pd SCH carbonyl oxygen atom carbonyl carbon atom Thioether Complexes CH bidentate thioether ligand disfavors water molecule Artificial Peptidases residue Y