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Uptake of potential anti-diabetic VIVO compounds of picolinate ligands by red blood cells

Sanna, Daniele and Serra, Maria and Micera, Giovanni and Garribba, Eugenio (2014) Uptake of potential anti-diabetic VIVO compounds of picolinate ligands by red blood cells. Inorganica Chimica Acta, Vol. 420 , p. 75-84. ISSN 0020-1693. Article.

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DOI: 10.1016/j.ica.2013.12.038

Abstract

The interaction of three potential anti-diabetic VIVO compounds formed by picolinate (pic), 3-methylpicolinate (3-mepic) and 6-methylpicolinate (6-mepic) with hemoglobin (Hb) and red blood cells was studied with the combined application of spectroscopic (EPR), spectrophotometric (UV-Vis) and computational (DFT methods) techniques. In the ternary systems with hemoglobin, pic and 3-mepic (L) form mixed species cis-VOL2(Hb), with the equatorial binding of an accessible His residue, whereas 6-mepic forms VO(6-mepic)(OH)(Hb). The experiments about the uptake of VIVO complexes by red blood cells indicate that only [VO(pic)2(H 2O)] penetrates the erythrocyte membrane in a significant amount, whereas for [VO(3-mepic)2] and [VO(6-mepic)2] the hydrolytic reactions at physiological pH hinder the diffusion in the intracellular medium. Inside the red blood cells, the biotransformations depend mainly on the strength of the ligand. Pic and 3-mepic form cis-VOL2(Hb) and cis-VOL2(Cys-S-) with the equatorial coordination of a thiolate-S- stemming from GSH or a membrane protein. Instead, the less thermodynamically stable compound, [VO(6-mepic) 2], loses the two ligands after the interaction with the membrane or inside the erythrocytes to give the same species formed by free V IVO2+ ion: (VO)Hbβ and (VO)Hb γ, with VIVO2+ coordinated to the sites β and γ of hemoglobin, and VO(L1,L2) and VO(L3,L4), where L1, L2, L 3 and L4 are generic red blood cell bioligands, such as proteins (for example, Hb) or low molecular mass (l.m.m.) components. The distribution of an insulin-enhancing V compound between the serum and the red blood cells may influence the mechanism of action and the activity of a V drug and explain the different effectiveness observed in the literature.

Item Type:Article
ID Code:9980
Status:Published
Refereed:Yes
Uncontrolled Keywords:Anti-diabetic compounds, bioinorganic chemistry, EPR spectroscopy, erythrocytes, hemoglobin, vanadium
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
002 Altri enti e centri di ricerca del Nord Sardegna > CNR-Consiglio Nazionale delle Ricerche > Istituto di chimica biomolecolare, Sassari
Publisher:Elsevier
ISSN:0020-1693
Additional Information:Recent Advances in Vanadium Chemistry Special Issue
Deposited On:21 Jul 2014 17:40

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