Complex formation equilibria of Cu2+ and Zn2+ with Irbesartan and Losartan

Abstract

We conducted a thorough study of Cu 2+ 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 toward Cu 2+. 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 Zn 2+ 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 Zn 2+ -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 Cu 2+ from the organism.

Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy

“…Serum zinc content also decreases with captopril (50-150 mg/day), verapamil (240 mg/day), atenolol (50-150 mg/day), and the combination of losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day). All listed drugs have different metal-binding sites and form stable complexes not only with zinc but also with copper ions [113]. The possibility that long-term use of antihypertensive drugs affects zinc and copper homeostasis and pharmacokinetics must be taken into consideration in the treatment of patients with conditions correlated with the unbalance of zinc homeostasis, such as diabetes, liver cirrhosis, bowel diseases, and impaired immune function [114].…”

Interaction of Zn with Losartan. Activation of Intrinsic Apoptotic Signaling Pathway in Lung Cancer Cells and Effects on Alkaline and Acid Phosphatases

“…1). The thermal, spectroscopic characterization, antioxidant evaluation (against 1,1diphenyl-picrylhydrazyl, DPPH) and the pyrolysis [12] and the complex formation equilibria of losartan with Zn(II) [13], [Zn(Los) 2 ].3H 2 O (ZnLos), have recently been reported. Here, we report some spectroscopic characterizations and the biological studies of this solid complex.…”