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

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.