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

In vitro influence of five synthesized functionalized hexavanadates (V-6) 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 x 10(-5), 1.8 x 10(-5), 2.9 x 10(-5), 5.5 x 10(-5) for functionalized hexavanadates (V-6) with tetrabutylammonium (TBA) [V-6-CH3][TBA](2), [V-6-NO2][TBA](2), [V-6-OH][TBA](2) and [V-6-C-3][TBA](2) respectively. [V-6-OH][Na](2) inhibited Na+/K+-ATPase activity up to 30% at maximal investigated concentration 1 x 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 center dot center dot center dot 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 V-6. These results enlightened their chemical reactivity and their potential biological applications such as the inhibition of the ATPase. (C) 2016 Elsevier Inc. All rights reserved.