Speciation in aqueous solution and interaction with low and high molecular mass blood bioligands of [VIVO(oda)(H2O)2], a V compound with in vitro anticancer activity

In this work the speciation in aqueous solution of the compound [VIVO(oda)(H2O)2], where oda is oxydiacetate dianion (OOCCH2)2O, which shows in vitro anticancer activity, was studied. Its interaction with the two serum bioligands with highest affinity for VIV, lactic (Hlact) and citric (H3citr) acid, and with the two proteins candidate to participate to the transport of VIVO 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)(H2O)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)(H2O)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 VIVO-oda-lact was observed. [VO(oda)(H2O)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)(H2O)2] is administered orally (concentration ca. 1-10 ?M) or by injection (concentration approximately in the range 10-100 ?M), (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.