Dawson- and Lindqvist-Type Hybrid Polyoxometalates: Synthesis, Characterization and Ca2+-ATPase Inhibition Potential

Abstract

Polyoxometalates (POMs) represent a broad class of anionic inorganic (V, Mo, W) clusters with versatile structures of chemical and physical properties. POMs are inhibitors of many enzymes, including P-type ATPases, well-known to be a target of several approved drugs. Herein, two new hybrid POMs with Mo and mixed V/W, namely (C2H8N1)(6)[V2Mo18O62].3H(2)O (1) and (C4H16N3)(4)[V2W4O19](3).12H(2)O (2), were synthesized via wet chemical methods in aqueous solution, and their purity was confirmed and characterized by single X-ray diffraction and infrared spectroscopy. The cations are dimethylammonium ((C2H8N)(+)) and diethylenetriammonium ((C4H16N3)(3+)), respectively. POMs biological activities were investigated, specifically their inhibitory potential against Ca2+-ATPase. The sarcoplasmic reticulum Ca2+-ATPase activities were measured spectrophotometrically using the coupled enzyme pyruvate kinase/lactate dehydrogenase assay. For the Ca2+-ATPase activity, Dawson (1) showed an IC50 value of 3.4 mu M, whereas Lindqvist (2) displayed a value of 45.1 mu M. The Ca2+-ATPase inhibitory potential of these POMs can be correlated with the net charge (namely 6- and 4-) and the charge density (namely 0.33 and 0.67). A structure-activity-relationship was established for a series of 17 POMs Ca2+-ATPase inhibitors correlating IC50 values and POMs net charge and POMs charge density. The described features make Dawson (1) and Lindqvist (2) attractive POMs in a wide range of chemistry fields as well as in biomedical applications.