Titolo:  Complex formation equilibria of Cu2 + and Zn2 + with Irbesartan and Losartan
Data di pubblicazione:  2017
Data di prima pubblicazione on-line:  2016
Autori: 
Autori:  Lachowicz, Joanna Izabela; Nurchi, Valeria Marina; Crisponi, Guido; Jaraquemada-Pelaez, Maria de Guadalupe; Caltagirone, Claudia; Peana, Massimiliano; Zoroddu, Maria Antonietta; Szewczuk, Zbigniew; Cooper, Garth J.S.
Numero degli autori:  9
Lingua:  Inglese
Presenza coautori internazionali: 
Rivista:  EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume:  97
Pagina iniziale:  158
Pagina finale:  169
Numero di pagine:  12
Digital Object Identifier (DOI):  http://dx.doi.org/10.1016/j.ejps.2016.11.010
Codice identificativo Pubmed:  27838251
Codice identificativo Scopus:  2-s2.0-84995939752
Codice identificativo ISI:  WOS:000390699500018
URL:  http://www.sciencedirect.com/science/article/pii/S0928098716304894
Parole Chiave:  Diabetes; Metal coordination; Sartans; Spectroscopy; Tautomers; 3003
Abstract:  We conducted a thorough study of Cu2 + complex formation equilibria with Irbesartan and Losartan, the two primary drugs for the cure of cardiovascular diseases, with the aim of recognising if these drugs could exert a chelating action towards Cu2 +. We used different complementary techniques to gain a clear picture of the involved protonation and complexation equilibria. The low solubility in water of the ligands and of the formed metal complexes prevented the use of water as solvent, so we had to perform the measurements in mixed methanol-water solvents. Further, we studied the related equilibria with Zn2 + for evaluating a potential interference of this essential metal ion, largely present in biological fluids. Our study provided a strong evaluation of the formed complexes and of the relative stability constants. The binding of both metal ions takes place through the tetrazole moiety except for the Zn2 +-Irbesartan system. In this last case, NMR measurements gave evidence of a tautomeric equilibrium involving the imidazole ring and the aliphatic chain. The estimated complexation model, and the related stability constants, allowed a speciation study in human plasma, based on a number of simplifying assumptions, which remarked that both drugs, Losartan and Irbesartan, could exert a chelating action, scavenging non-negligible amounts of Cu2 + from the organism.
Tipologia: 1.1 Articolo in rivista

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