Investigation of Vanadocene(IV) α-Amino Acid Complexes:  Synthesis, Structure, and Behavior in Physiological Solutions, Human Plasma, and Blood

This work is focused on investigating the interaction of antitumor active metallocene vanadocene dichloride (Cp<sub>2</sub>VCl<sub>2</sub>) and amino acids in aqueous solution at physiological pH. Sixteen vanadocene amino acid complexes [Cp<sub>2</sub>V(aa)][X] (aa = gly, ala, val, leu, ile, phe, his, and trp; X = Cl, PF<sub>6</sub>) were prepared and characterized on the basis of spectral measurements (EPR, MS, IR, Raman). Amino acids are coordinated to the vanadocene fragment through the oxygen atom of the carboxylic group and the nitrogen of the amino group, resulting in a five-membered chelate ring. Complexes [Cp<sub>2</sub>V(val)][PF<sub>6</sub>] and [Cp<sub>2</sub>V(ile)][PF<sub>6</sub>] have been characterized by X-ray structure analyses. It was evidenced that all prepared complexes are stable in both aqueous solutions with physiological pH and in therapeutic NaCl solutions. EPR spectra of vanadocene amino acid complexes in Krebs−Ringer solution in human blood plasma and in whole blood showed that these complexes react with the hydrogen carbonate anion present forming complex Cp<sub>2</sub>V(O<sub>2</sub>CO).