Role of Ligands in the Uptake and Reduction of V(V) Complexes in Red Blood Cells

Daniele Sanna, Jessica Palomba, Giuseppe Lubinu, P. Buglyó, Sándor Nagy, Franc Perdih, Eugenio Garribba

Research output: Contribution to journalArticle

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Abstract

The interaction with erythrocytes of four [VVO2L2]- complexes, with L = picolinate (pic), 5-cyanopicolinate (picCN), 3-aminopyrazine-2-carboxylate (przNH2), and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (dhp), was studied. The thermodynamic stability at physiological pH is: [VVO2(dhp)2]- > [VVO2(przNH2)2]- > [VVO2(pic)2]- > [VVO2(picCN)2]-. With picCN and pic, V exists at physiological pH as H2VVO4 -, with przNH2 as a mixture of H2VVO4 - and [VVO2(przNH2)2]- and with dhp as [VVO2(dhp)2]-. In the systems with pic and picCN, H2VVO4 - and the ligands cross the erythrocyte membrane independently, with dhp the uptake occurs by diffusion, whereas with przNH2 both the mechanisms are active. Inside erythrocytes stable VIVOL2 complexes are formed, indicating that there is no relationship with the stability and redox state of the administered compounds and that, if the metal ion changes its oxidation state in the cytosol as V does, unstable complexes in the extracellular medium could become stable inside the cells and contribute to the pharmacological action.

Original languageEnglish
Pages (from-to)654-664
Number of pages11
JournalJournal of Medicinal Chemistry
Volume62
Issue number2
DOIs
Publication statusPublished - Jan 24 2019

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Erythrocytes
Ligands
Erythrocyte Membrane
Thermodynamics
Cytosol
Oxidation-Reduction
Metals
Pharmacology
Ions
oligomycin sensitivity-conferring protein
picolinic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Role of Ligands in the Uptake and Reduction of V(V) Complexes in Red Blood Cells. / Sanna, Daniele; Palomba, Jessica; Lubinu, Giuseppe; Buglyó, P.; Nagy, Sándor; Perdih, Franc; Garribba, Eugenio.

In: Journal of Medicinal Chemistry, Vol. 62, No. 2, 24.01.2019, p. 654-664.

Research output: Contribution to journalArticle

Sanna, Daniele ; Palomba, Jessica ; Lubinu, Giuseppe ; Buglyó, P. ; Nagy, Sándor ; Perdih, Franc ; Garribba, Eugenio. / Role of Ligands in the Uptake and Reduction of V(V) Complexes in Red Blood Cells. In: Journal of Medicinal Chemistry. 2019 ; Vol. 62, No. 2. pp. 654-664.
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