Tuning the Selectivity and Reactivity of Metal-Substituted Polyoxometalates as Artificial Proteases by Varying the Nature of the Embedded Lewis Acid Metal Ion

The hydrolysis of horse heart cytochrome c (cytC) protein by two isostructural Keggin-type polyoxometalates (POMs), (Me2NH2)(10)[Ce(-PW11O39)(2)] (Ce1-K2) and (Et2NH2)(10)[Zr(PW11O39)(2)] (Zr1-K2), which differ in the nature of the embedded Lewis acid metal ion, has been investigated. In the presence of Ce1-K2, selective hydrolysis of cytC was observed at the Trp60-Lys61 and Gly78-Thr79 peptide bonds at pH 7.4 and 37 degrees C. However, the isostructural Zr1-K2 exhibited a lower reactivity and different selectivity, cleaving cytC at the Asp3-Val4, Asp51-Ala52 and Gly78-Thr79 peptide bonds. Different spectroscopic techniques were used to verify the molecular interactions between cytC and each metal-substituted Keggin POM to elucidate the role of the Lewis acid metal ion in directing the selectivity of protein hydrolysis.