For more than a century, the anti-diabetic properties of a variety of vanadium-containing complexes have been studied but more recently their anti-cancer activities have generated intense interest because of a combination of desirable properties for chemotherapy, i.e., strong cytotoxicities, anti-metastatic activities and relatively low systemic toxicities. However, many vanadium complexes have been shown to be active due to release of cytotoxic ligands in the medium rather than target cells, which limits their chemotherapeutic value. It is therefore important to study the stability of the compounds in the media in which they are studied. The vanadium(V) precursor [V(O)2(Hshed)] and two V(V) catecholate substituted anologues, [VO(Hshed)(cat)] and [VO(Hshed)(dtb)], (Hshed = N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine, cat = pyrocatechol, and dtb = 3,5-di(tert-butyl)catechol were synthesized. Using 51V and 1H solution NMR spectroscopy, the location of the free ligands, cat and dtb, the three V complexes [V(O)2(Hshed)], were determined in a reverse micelle (RM) model membrane system. Vanadium(V) complexes generally undergo hydrolysis upon introduction in aqueous solution; therefore, the stability of the above three complexes were measured within an aqueous environment and a RM system. The decomposition of the V(V) precursor and the V(V) catecholates within aqueous solution and a RM interface and the resulting hydrolysis products were characterized. Our results demonstrated that the free ligands and the three V(V) complexes all penetrated the RM interface and the three V complexes all hydrolyzed to a certain extent into various vanadate oligomers. Reactions were also studied in PBS and cell medium using UV/Vis spectroscopy and global kinetic analysis, which showed similar reactivities for an individual complex in solutions at 37 °C. Combined this shows that the membrane permeability studies are directly applicable to the conditions to in-vitro cytotoxicity assays and suggests that [VO(hshed)(dtb)] can pass through the cellular membrane intact to impart its promising anti-cancer activities.

Schiff-base vanadium(V) catecholate complexes and their interactions with a model membrane interface

255th National Meeting (2018)

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