A combined crystallographic analysis and ab initio calculations to interpret the reactivity of functionalized hexavanadates and their inhibitor potency toward Na+/K+-ATPase

•Functionalized hexavanadates (V6) inhibit Na+/K+-ATPase.•[V6–OH][Na]2 inhibited Na+/K+-ATPase activity up to 30% at max. investigated concentration.•The O2x bridged oxygen atoms are more reactive than O1x terminal oxygen.•The protonation sites in the cage are oxygen atoms of type O2x.•The most charged V–O1x bond belongs to [V6–NO2][TBA]2 TBA, tetrabutylammonium

In vitro influence of five synthesized functionalized hexavanadates (V6) on commercial porcine cerebral cortex Na+/K+-ATPase activity has been studied. Dose dependent Na+/K+-ATPase inhibition was obtained for all investigated compounds. Calculated half maximal inhibitory concentration IC50 values, in mol/L, for Na+/K+-ATPase were 7.6 × 10− 5, 1.8 × 10− 5, 2.9 × 10− 5, 5.5 × 10− 5 for functionalized hexavanadates (V6) with tetrabutylammonium (TBA) [V6–CH3][TBA]2, [V6–NO2][TBA]2, [V6–OH][TBA]2 and [V6–C3][TBA]2 respectively. [V6–OH][Na]2 inhibited Na+/K+-ATPase activity up to 30% at maximal investigated concentration 1 × 10− 3 mol/L. This reactivity has been interpreted using a study of the non-covalent interactions of functionalized hexavanadate hybrids through Cambridge Structural Database (CSD) analysis. Bibliographic searching has led to 18 different structures and 99 contacts. We have observed that C–H ⋯ O contacts consolidate the structures. We have also performed density functional theory (DFT) calculations and have determined electrostatic potential values at the molecular surface on a series of functionalized V6. These results enlightened their chemical reactivity and their potential biological applications such as the inhibition of the ATPase.

Graphical abstractFive compounds of hexavanadates (V6) were synthesized and their inhibitor potency toward Na+/K+-ATPase was investigated. Investigated hexavanadates showed inhibitory effect on Na+/K+-ATPase activity. Analysis of noncovalent interactions between V6 and organic part using the Cambridge Structural Database was performed.Figure optionsDownload full-size imageDownload as PowerPoint slide