Interaction of [V^IVO(acac)₂] with Human Serum Transferrin and Albumin

Abstract

[VO(acac) ] is a remarkable vanadium compound and has potential as a therapeutic drug. It is important to clarify how it is transported in blood, but the reports addressing its binding to serum proteins have been contradictory. We use several spectroscopic and mass spectrometric techniques (ESI and MALDI-TOF), small-angle X-ray scattering and size exclusion chromatography (SEC) to characterize solutions containing [VO(acac) ] and either human serum apotransferrin (apoHTF) or albumin (HSA). DFT and modeling protein calculations are carried out to disclose the type of binding to apoHTF. The measured circular dichroism spectra, SEC and MALDI-TOF data clearly prove that at least two VO-acac moieties may bind to apoHTF, most probably forming [V O(acac)(apoHTF)] complexes with residues of the HTF binding sites. No indication of binding of [VO(acac) ] to HSA is obtained. We conclude that V O-acac species may be transported in blood by transferrin. At very low complex concentrations speciation calculations suggest that [(VO)(apoHTF)] species form.

A Short‐Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections

“…These serum proteins also led to % 6-fold decrease in cellular V content from the treatment of T98g cells with 50 mm 1 for 4 h ( Figure S4). Thus, contrary to literature postulates, [19] V binding to Tf is not required for its cellular uptake and cytotoxicity, as described elsewhere. [21] The higher cytotoxicity of fresh 1 vs. its decomposition products in all cell lines ( Figure 2) correlated with higher cellular V content ( Figure S4).…”

Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

“…indicates that the neutral compounds penetrate the erythrocyte membrane through passive diffusion, being found in the intracellular medium in amounts higher than 50%. Alternatively, inside the red blood cells, the compounds [V IV O(mal) 2 Finally, studies concerning to the transport of vanadium complexes in blood, concluded that vanadium complexes are mostly transported by transferrin (hTf) [69][70][71][72][73]. At low micromolar concentrations, assuming that V(IV) maintains its oxidation state, most of the complexes hydrolyse and vanadium(IV) is transported as (VO)hTf, with V(IV)O bound at one of the iron sites [69][70][71][72][73].…”

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends

“…It has been reported that V in the form of vanadyl (VO 2+ , tetravalent V 4+ state) binds to Tf at the same binding site as the Fe 3+ ion [97] and that V 5+ , for which the cationic form (dioxovanadium cation, VO2 + ) has been indicated, also occupies the same pockets as Fe 3+ [98]. Studies conducted by Azevedo et al [99] have confirmed that both V 4+ and V 5+ can bind to apo-Tf and holo-Tf, thus they can be efficiently up-taken by cells through receptor-mediated endocytosis of Tf.…”