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