title: Complex formation equilibria of Cu2+and Zn2+with Irbesartan and Losartan.
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.
authors.affiliation: Department of Chemical and Geological Science, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy. Electronic address: lachowicz@unica.it.
authors.forename: Joanna Izabela
authors.initials: JI
authors.lastname: Lachowicz
authors.affiliation: Department of Chemical and Geological Science, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy.
authors.forename: Valeria Marina
authors.initials: VM
authors.lastname: Nurchi
authors.affiliation: Department of Chemical and Geological Science, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Crisponi
authors.affiliation: Department of Chemical and Geological Science, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy.
authors.forename: Maria de Guadalupe
authors.initials: MG
authors.lastname: Jaraquemada-Pelaez
authors.affiliation: Department of Chemical and Geological Science, University of Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, I-07100 Sassari, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Peana
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, I-07100 Sassari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zoroddu
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot Curie 14, 50-383 Wroclaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szewczuk
authors.affiliation: Central Manchester NHS Hospitals Foundation Trust, and School of Biomedicine, The University of Manchester, and Manchester Academic Health Sciences Centre, Manchester, UK; School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, Faculty of Science, University of Auckland, Auckland 1010, New Zealand.
authors.forename: Garth J S
authors.initials: GJ
authors.lastname: Cooper
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000737:chemistry* / Q000493:pharmacokinetics; D003300:Copper / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D000077405:Irbesartan; D019808:Losartan / Q000737:chemistry* / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D015032:Zinc / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D056831:Coordination Complexes; D013777:Tetrazoles; D003300:Copper; D000077405:Irbesartan; D015032:Zinc; D019808:Losartan
keywords: Diabetes; Metal coordination; Sartans; Spectroscopy; Tautomers