Hydrolysis of Dipeptides Catalyzed by a Zirconium(IV)-Substituted Lindqvist Type Polyoxometalate

Abstract

The hydrolysis of a series of unactivated dipeptides in the presence of a zirconium(IV)-substituted Lindqvist type polyoxometalate (Me₄N)₂[W₅O₁₈Zr(H₂O)₃], designated as ZrW₅, was studied by kinetic experiments and NMR spectroscopy. Among all the examined dipeptides those with a general X-Ser amino acid sequence were most effectively hydrolyzed. Detailed kinetic studies were performed on the hydrolysis of histidylserine (His-Ser), for which a rate constant of 95.3 ( ±0.1)x10⁻⁷ s⁻¹ (pD 7.4 and 60°C) in the presence of equimolar amounts of ZrW₅ was calculated. The binding of His-Ser to ZrW₅ was examined by UV-Vis, ¹H, ¹³C and ¹⁸³W NMR spectroscopy and the data indicate that at physiological pD His-Ser chelates to the Zrᶦᵛ through its imidazole nitrogen, amine nitrogen, and amide carbonyl oxygen. In the presence of ZrW₅, the pD profile of kobs displays a bell-shaped profile with a maximum reaction rate at pD 7.5. At high pD values an inactive complex is formed due to the deprotonation of the amide nitrogen, resulting in inhibition of His-Ser hydrolysis. The effect of pH, temperature, inhibitors, and ionic strength on the hydrolysis rate constant was also investigated and a full account of the mechanism of this novel reaction is given.