Tantalum(v) peroxido complexes as phosphatase inhibitors: a comparative study vis-a-vis peroxidovanadates

The present work illustrates the synthesis and comprehensive characterization of novel peroxidotantalum(v) complexes anchored to water soluble polymer (WSP) matrices viz., [Ta-2(O-2)(6)(carboxylate)(2)]-PA [PA = poly(sodium acrylate)] (PATa) and [Ta(O-2)(3)(sulfonate)(2)]-PSS [PSS = poly(sodium 4-styrene sulfonate)] (PSSTa) and their identification as potent inhibitors of acid phosphatase (ACP) activity. Using a set comprising tantalum(v) and vanadium(v) peroxides in similar macro ligand environments, and wheat thylakoid acid phosphatase as a model enzyme, it has been demonstrated for the first time that peroxidotantalum (pTa) derivatives are 2-3 fold more active as ACP inhibitors (IC50: 0.34 mu M for PSSTa) compared to their V containing analogues (IC50: 1.22 mu M). Enzyme kinetics analysis further revealed that the pTa and peroxidovanadate (pV) compounds tested, irrespective of the nature of their ligand environment, inhibit ACP function exclusively via a non-competitive pathway with K-i and K-ii values ranging between 0.2 and 4.7 mu M. Importantly, under the effect of the enzyme catalase, the pTa compounds with a rate of peroxide loss as low as 0.92 mu M min(-1) (PATa) emerged to be remarkably more resistant to degradation relative to the corresponding pV compound, which degraded at a significantly faster rate (5.80 mu M min(-1)).