The interaction with erythrocytes of four [V^VO₂L₂]^- complexes, with L = picolinate (pic), 5-cyanopicolinate (picCN), 3-aminopyrazine-2-carboxylate (przNH₂), and 1,2-dimethyl-3-hydroxy-4(1 H)-pyridinonate (dhp), was studied. The thermodynamic stability at physiological pH is: [V^VO₂(dhp)₂]^- > [V^VO₂(przNH₂)₂]^- > [V^VO₂(pic)₂]^- > [V^VO₂(picCN)₂]^-. With picCN and pic, V exists at physiological pH as H₂V^VO₄^-, with przNH₂ as a mixture of H₂V^VO₄^- and [V^VO₂(przNH₂)₂]^- and with dhp as [V^VO₂(dhp)₂]^-. In the systems with pic and picCN, H₂V^VO₄^- and the ligands cross the erythrocyte membrane independently, with dhp the uptake occurs by diffusion, whereas with przNH₂ both the mechanisms are active. Inside erythrocytes stable V^IVOL₂ complexes are formed, indicating that there is no relationship with the stability and redox state of the administered compounds and that, if the metal ion changes its oxidation state in the cytosol as V does, unstable complexes in the extracellular medium could become stable inside the cells and contribute to the pharmacological action.

Jessica Palomba

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