Probing molecular interactions of an anti-epileptic drug, sodium valproate in aqueous MgCl2 solutions

Abstract

Study of the physicochemical properties of anti-epileptic drugs in the presence of cosolutes in aqueous solutions has been a subject of interest of researchers because of their interaction with biological membranes to employ their effect. Such properties provide complete information regarding solute-solute and solute-solvent type interactions. As electrolytes are essential components of biological systems, therefore the study of drug-electrolyte chemistry is important to understand the mechanism of drug action at the molecular level and hence useful in drug design and development processes. Therefore, in the current report, the density and sound velocity of an anti-epileptic drug sodium valproate (SV) in aqueous and in aqueous solutions of an electrolyte viz. MgCl2 (mB = 0.024, 0.047, 0.070 mol kg−1) at different temperatures (288.15, 298.15, 308.15, and 318.15 K) and at a pressure of 0.101 MPa were measured along with 1H NMR spectroscopy. Various volumetric and acoustical parameters such as apparent molar volume (Vφ) and isentropic compressibility (Kφ) of the solute, apparent molar volume (Vφ°) and isentropic compressibility (Kφ°) of solute at infinite dilution, apparent molar expansibility (Eφ°) and their double derivatives (∂2Vφ°/∂T2)P, transfer volumes (∆trVφ°), hydration number (nH), acoustic impedance (Z), intermolecular free length (Lf), Wada's constant (W) and Rao's constant (R) were calculated from density and sound velocity data. The variation in all these parameters with cosolute concentration indicates the existence of hydrophilic/ionic-ionic interactions at lower concentrations but hydrophobic-ionic interactions at higher concentrations of MgCl2. The 1H NMR spectroscopic results also support the existence of hydrophobic-ionic interactions at higher concentrations of MgCl2. The decrease in electrostriction but increase in hydrophobic hydration of solute molecules has also been seen with rise in temperature.