Peptide Bond Hydrolysis Catalyzed by the Wells–Dawson Zr(α₂‑P₂W₁₇O₆₁)₂ Polyoxometalate

In this paper we report the first example of peptide hydrolysis catalyzed by a polyoxometalate complex. A series of metal-substituted Wells–Dawson polyoxometalates were synthesized, and their hydrolytic activity toward the peptide bond in glycylglycine (GG) was examined. Among these, the Zr­(IV)- and Hf­(IV)-substituted ones were the most reactive. Detailed kinetic studies were performed with the Zr­(IV)-substituted Wells–Dawson type polyoxometalate K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O which was shown to act as a catalyst for the hydrolysis of the peptide bond in GG. The speciation of K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O which is highly dependent on the pD, concentration, and temperature of the solution, was fully determined with the help of ³¹P NMR spectroscopy and its influence on the GG hydrolysis rate was examined. The highest reaction rate (<i>k</i>_obs = 9.2 (±0.2) × 10^–5 min^–1) was observed at pD 5.0 and 60 °C. A 10-fold excess of GG was hydrolyzed in the presence of K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O proving the principles of catalysis. ¹³C NMR data suggested the coordination of GG to the Zr­(IV) center in K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O via its N-terminal amine group and amide carbonyl oxygen. These findings were confirmed by the inactivity of K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O toward the N-blocked analogue acetamidoglycylglycinate and the inhibitory effect of oxalic, malic, and citric acid. Triglycine, tetraglycine, and pentaglycine were also fully hydrolyzed in the presence of K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O yielding glycine as the final product of hydrolysis. K₁₅H­[Zr­(α₂-P₂W₁₇O₆₁)₂]·25H₂O also exhibited hydrolytic activity toward a series of other dipeptides