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

Abstract

The present work illustrates the synthesis and comprehensive characterization of novel peroxidotantalum(V) complexes anchored to water soluble polymer (WSP) matrices viz., [Ta₂(O₂)₆(carboxylate)₂]–PA [PA = poly(sodium acrylate)] (PATa) and [Ta(O₂)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 μM for PSSTa) compared to their V containing analogues (IC₅₀: 1.22 μM). 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 μM. Importantly, under the effect of the enzyme catalase, the pTa compounds with a rate of peroxide loss as low as 0.92 μM 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 μM min⁻¹).