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

Daniele Sanna, Valeria Ugone, P. Buglyó, Sándor Nagy, István Kacsir, Eugenio Garribba

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)127-138
Number of pages12
JournalInorganica Chimica Acta
Volume472
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Vanadium
Molecular mass
Transferrin
Citric Acid
blood
Density functional theory
Paramagnetic resonance
Albumins
Blood
aqueous solutions
Citric acid
Isomers
Anions
Hydrolysis
Lactic Acid
albumins
Negative ions
Iron
Ligands
vanadium

Keywords

  • Antitumor compounds
  • Biospeciation
  • Medicinal inorganic chemistry
  • Vanadium

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Materials Chemistry

Cite this

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. / Sanna, Daniele; Ugone, Valeria; Buglyó, P.; Nagy, Sándor; Kacsir, István; Garribba, Eugenio.

In: Inorganica Chimica Acta, Vol. 472, 01.03.2018, p. 127-138.

Research output: Contribution to journalArticle

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abstract = "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 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.",
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AU - Buglyó, P.

AU - Nagy, Sándor

AU - Kacsir, István

AU - Garribba, Eugenio

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