Speciation in aqueous solution and interaction with low and high molecular mass blood bioligands of [V IV O(oda)(H 2 O) 2 ], a V compound with in vitro anticancer activity

Abstract

Abstract In this work the speciation in aqueous solution of the compound [V IV O(oda)(H 2 O) 2 ], where oda is oxydiacetate dianion (OOCCH 2 ) 2 O, which shows in vitro anticancer activity, was studied. Its interaction with the two serum bioligands with highest affinity for V IV , lactic (Hlact) and citric (H 3 citr) acid, and with the two proteins candidate to participate to the transport of V IV O compounds in the organism, transferrin (hTf) and albumin (HSA), was also examined. The study was carried out with the combined application of spectroscopic (Electron Paramagnetic Resonance, EPR), analytical (pH-potentiometry) and computational (Density Functional Theory, DFT) methods. The results showed that in aqueous solution [VO(oda)(H 2 O) 2 ] undergoes hydrolysis above pH 4–5 with formation of the EPR-active species [(VO) 2 (oda) 2 (OH) 2 ] 2− around pH 6 and of [(VO) 2 (OH) 5 ] − at physiological pH. DFT calculations suggested that the most stable isomers of 1:1 species are the hexa-coordinated OC -6-23 with a mer arrangement of oda – similar to that observed in the solid state – and the penta-coordinated SPY -5-14, whereas for 1:2 species the fac arrangement of oda is favored. Citrate is able to displace completely the oda ligand in [VO(oda)(H 2 O) 2 ] and only the dinuclear species [(VO) 2 (citrH -1 ) 2 ] 4− was detected at pH 7.4, while with lactate the formation of a mixed complex V IV O–oda–lact was observed. [VO(oda)(H 2 O) 2 ] interacts with apo-transferrin forming a mixed complex (VO)(hTf)(oda) where vanadium is bound in the iron sites and oda behaves as a synergistic anion, while with albumin no interaction was revealed. Model calculations suggest that when [VO(oda)(H 2 O) 2 ] is administered orally (concentration ca . 1–10 μM) or by injection (concentration approximately in the range 10–100 μM), (VO)(hTf) and (VO) 2 (hTf) should be formed; these species could reach the target organs and be recognized by the hTf receptors of the cells, favoring the vanadium uptake.