Solubility, potentiometric and thermodynamic studies on zinc-bosentan complex; synthesis and X-ray crystal structure

Abstract

A zinc-complex, [ZnL2]center dot 2.5 EtOH, of bosentan (HL) is synthesized and characterized by UV-Vis and FT-IR spectroscopies and single crystal X-ray diffraction. X-ray crystal structural analysis indicates that the zinc complex crystallized in the triclinic space group P-1 and adopts a distorted octahedral coordination geometry. Solubility and dissolution profiles of bosentan and the complex were studied at three different pH 0.4, 7.4 and 8.5 in aqueous solution. Solubility of bosentan and the complex at studied pH is changed as follows: 0.4 > 8.5 > 7.4. In all studied pHs dissolution rate of bosentan and the complex is high in the first 9 h in addition maximum solubility of bosentan and the complex occurs at pH 0.4. The protonation constants of bosentan and its stability constants in presence of Zn2+ are determined potentiometrically using the BEST computer program. The potentiometric studies were carried out in 0.1 M Me4NCl at three different temperatures (25, 37 and 45 degrees C) among pH range of 2.0-12.0 at various concentrations (50-90% v/v) of ethanol + water mixtures. Various complex species, MLH, ML and MLH-1, were formed at various pHs. The protonation constant of bosentan and stability constants of complex species increased with increasing the ethanol content of mixed solvent. The effect of temperature on protonation constant of bosentan and stability constant of the complex species was studied at 25, 37 and 45 degrees C and the corresponding thermodynamic parameters (G Delta degrees, Delta H degrees and Delta S degrees) were derived. The protonation process and the complex formation (ML) are spontaneous, endothermic and entropically favorable. (C) 2017 Published by Elsevier B.V.