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Dawson- and Lindqvist-Type hybrid polyoxometalates: synthesis, characterization and Ca2+-ATPase inhibition potential

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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].3H2O (1) and (C4H16N3)4[V2W4O19]3.12H2O (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 μM, whereas Lindqvist (2) displayed a value of 45.1 μM. 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.

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Polyoxometalates Ca2+-ATPase inhibitors POMs synthesis Coupled enzyme pyruvate kinase/lactate dehydrogenase assay Structure-activity correlations

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