Speciation and structural transformation of a VV-malate complex in the absence and in the presence of a protein: from a dinuclear species to decavanadate

Abstract

A strategy for the development of new vanadium-based drugs is the preparation of complexes that target proteins and bear molecules involved in the cellular metabolism as ligands, like αhydroxycarboxylic acids. Based on these premises this study explores the solution behaviour of the dioxovanadium(V) complex of malic acid, Cs₂[V^V₂O₄(mal)₂]•2H₂O, and its interaction with the model protein lysozyme (HEWL) at room and at physiological temperature using ⁵¹V nuclear magnetic resonance (NMR), electrospray ionisation-mass spectrometry and X-ray crystallography. The results show the coexistence in aqueous solution of various molecular species containing two or ten V^V centres. In solution these species are formed regardless of the presence of HEWL, while at 37°C the formation of [V^V₁₀O₂₈]^6- (V₁₀) decreases in the presence of the protein. Crystallographic data collected at pH 4.0 reveal that, when protein crystals are incubated with the V compound atare bound to the protein, while at 37°C only [V^IVO]²⁺ interacts with HEWL. [V^V₁₀O₂₈]^6- can bind the protein both covalently (as [V^V₁₀O₂₆]^2- ion) and non-covalently. Whereas the transformation of [V^V₂O₄(mal)₂]^2- to [V^V₂O₅(mal)]^2- is expected on the bases of thermodynamic considerations, the formation of V₁₀ and of the V₁₀-HEWL adduct is not easily predictable. Docking calculations confirm the experimental results and highlight the role of protein-protein interaction in the stabilization of the revealed adduct. This study demonstrates that vanadium compounds can undergo transformation in solution, giving rise to species that interact with proteins through several binding modes and stabilization mechanisms.