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ORIGINAL PAPER

Synthesis, Crystal Structure and Physicochemical Characterization of Two Ni(II)‑Famotidine Metal Complexes Marcos G. Russo1,2   · Juan C. Tenorio Clavijo3 · Natalia Alvarez4 · Hector A. Baldoni5 · Elena V. Brusau1,2 · Javier Ellena6 · Griselda E. Narda1,2 Received: 6 April 2020 / Accepted: 25 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The coordination ability of the antisecretor agent Famotidine (FMT) was explored using Ni(II) as central ion. ­[NiFMTH-2] and [Ni(FMT)2]Cl2 were obtained by the solvent evaporation method from the corresponding starting solutions at pH 8 and 4, respectively; the crystal structure was elucidated by single crystal X-ray diffraction in both cases.[NiFMTH-2] resulted in a distorted square-planar geometry, where FMT acts as a tetradentate dianionic ligand through nitrogen atoms belonging to the guanidine group, the thiazolic ring and the side chain, and a sulfur atom from the thioether moiety. [Ni(FMT)2]Cl2 exhibits an octahedral environment composed by two FMT molecules that coordinate by nitrogen atoms deriving from guanidine and thiazole ring moieties, and the thioether sulfur atom. The physicochemical characterization was completed by means of FTIR and UV–Vis spectroscopies, and thermal analysis. Solubility measurements were performed and the results could be satisfactorily correlated with the solvation Gibbs free energy (ΔGsolv) values in aqueous solution obtained using the SDM model by DFT calculations.

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1087​0-020-00860​-3) contains supplementary material, which is available to authorized users. Extended author information available on the last page of the article

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Journal of Chemical Crystallography

Graphic Abstract Ni(II) and famotidine form an octahedral complex at pH 4 where famotidine acts as a tridentate neutral ligand. In basic medium, it behaves as a tetradentate dianion, resulting in a quasi-planar complex. Spectroscopic and thermal data are consistent with single crystal X-ray diffraction structural elucidation. The relative stabilities were assessed by theoretical studies.

Keywords  Famotidine · Crystal structure · Physicochemical properties · Solubility · DFT calculation

Introduction Famotidine (FMT) is a histamine H2-receptor antagonist that competitively inhibits the action of histamine on parietal cells reducing the gastric acid secretion under daytime and nocturnal basal conditions. FMT is given to surgery patients before operations to prevent postoperative nausea and to reduce the risk of aspiration pneumonitis [1]. FMT is the 2019 125th most prescribed drug in the United States with more than 5 million prescriptions [2]. According to Biopharmaceutical Classification System [3], FMT is a IV class drug (low solubility–low permeability) and therefore, many studies have been performed to overcome this issue. Bilayered floating tablets for longer gastric residence time [4], FMT-loade