Vanadium complexes (VCs) are promising agents for the
treatment,
among others, of diabetes and cancer. The development of vanadium-based
drugs is mainly limited by a scarce knowledge of the active species
in the target organs, which is often determined by the interaction
of VCs with biological macromolecules like proteins. Here, we have
studied the binding of [VIVO(empp)2] (where
Hempp is 1-methyl-2-ethyl-3-hydroxy-4(1H)-pyridinone),
an antidiabetic and anticancer VC, with the model protein hen egg
white lysozyme (HEWL) by electrospray ionization-mass spectrometry
(ESI-MS), electron paramagnetic resonance (EPR), and X-ray crystallography.
ESI-MS and EPR techniques reveal that, in aqueous solution, both the
species [VIVO(empp)2] and [VIVO(empp)(H2O)]+, derived from the first one upon the loss
of a empp(−) ligand, interact with HEWL. Crystallographic data,
collected under different experimental conditions, show covalent binding
of [VIVO(empp)(H2O)]+to the side
chain of Asp48, and noncovalent binding ofcis-[VIVO(empp)2(H2O)], [VIVO(empp)(H2O)]+, [VIVO(empp)(H2O)2]+, and of an unusual trinuclear oxidovanadium(V)
complex, [VV3O6(empp)3(H2O)], with accessible sites on the protein surface.
The possibility of covalent and noncovalent binding with different
strength and of interaction with various sites favor the formation
of adducts with the multiple binding of vanadium moieties, allowing
the transport in blood and cellular fluids of more than one metal-containing
species with a possible amplification of the biological effects.