Interaction of V(V) complexes formed by picolinic and pyrazinecarboxylic acid derivatives with red blood cells

The interaction with red blood cells (RBC) of vanadium(V) complexes formed by 3,5-difluoropicolinic acid (HpicFF), 3-hydroxypicolinic acid (Hhypic) and pyrazinecarboxylic acid (Hprz) has been examined. Electron Paramagnetic Resonance (EPR) spectroscopy results suggest that V(V) is reduced in all cases to V(IV) inside the erythrocytes. The thermodynamic stability of V(V) and corresponding V(IV) complexes has been related with the species detected in the cellular environment; when the ligands form unstable complexes with both VO and VO ions (picFF and prz), the species formed inside RBC are similar to those observed when starting with vanadate(V) alone, that is VO - formed upon V(V) reduction - which distributes among the cellular bioligands forming different types of complexes. When in the ligand molecule other groups able to form chelated complexes are present (Hhypic), more stable species are formed inside the RBC. The amount of complex able to enter the RBC depends on the ligand structure which could influence the metal uptake. The interaction of different VO complexes formed by picolinate (picFF, pic = picolinate, picCN = 5-cyanopicolinate) and pyrazinecarboxylate (prz and przNH = 3-aminopyrazine-2-carboxylate) derivatives with hemoglobin (Hb), which is the main candidate to bind the VO ion in the cytosol, was also investigated to rationalize the results. The ligands which form at physiological pH relatively stable complexes with VO (przNH and pic) can give inside the erythrocytes mixed species after the replacement of an equatorial water molecule by an imidazole nitrogen of a histidine residue of the protein, while the ligands which form with VO unstable complexes (picCN, picFF, prz) yield the same species observed in the binary system VO-Hb.