110 Journal of Applied Solution Chemistry and Modeling, 2015, 4, 110-118 E-ISSN: 1929-5030/15 © 2015 Lifescience Global Preferential Solvation of the Antioxidant Agent Daidzein in some Aqueous Co-Solvent Mixtures according to IKBI and QLQC Methods Daniel M. Jiménez 1 , Zaira J. Cárdenas 1 , Daniel R. Delgado 2 , María Á. Peña 3 and Fleming Martínez 1,* 1 Grupo de Investigaciones Farmacéutico Fisicoquímicas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Cra. 30 No. 45-03, Bogotá D.C., Colombia 2 Programa de Ingeniería Industrial, Facultad de Ingeniería, Universidad Cooperativa de Colombia, Neiva, Colombia 3 Departamento de Ciencias Biomédicas, Facultad de Farmacia, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain Abstract: The preferential solvation parameters by ethanol (EtOH) or propylene glycol (PG) of daidzein were derived from their solution thermodynamic properties by means of the inverse Kirkwood-Buff integrals and the quasi-lattice- quasi-chemical (QLQC) methods. According to IKBI method, the preferential solvation parameter by the co-solvent, x1,3, is negative in water-rich mixtures but positive in co-solvent-rich mixtures in both kinds of systems. This could demonstrate the relevant role of hydrophobic hydration around the aromatic rings in the drug solvation in water-rich mixtures. Furthermore, the more solvation by co-solvent in co-solvent-rich mixtures could be due mainly to polarity effects and acidic behavior of the hydroxyl groups of the compound in front to the more basic solvents present in the mixtures, i.e. EtOH or PG. Otherwise, according to QLQC method, this drug is preferentially solvated by the co-solvents in all the mixtures in both kind of systems. Keywords: Daidzein, ethanol, propylene glycol, preferential solvation, inverse Kirkwood-Buff integrals, quasi-lattice- quasi-chemical. INTRODUCTION As has been widely described, phytoestrogens are a diverse group of naturally derived compounds that resemble 17-beta-estradiol (E 2 ) and they may protect against a wide range of bad conditions including several forms of cancer, cardiovascular disease, osteoporosis and menopausal symptoms [1]. In particular, some studies have indicated the possible effect in prevention of breast cancer [2]. Daidzein (Figure 1, IUPAC name: 7-Hydroxy-3-(4- hydroxyphenyl) chromen-4-one, molar mass: 254.23 g mol –1 , CAS 486-66-8) could be considered as a phyto- estrogen compound and it corresponds to an isoflavone, which is abundant in soybean [3]. It has been demonstrated to be a potent antioxidant and has gained relevance in relation to the human health [4]. Solubility determination of drugs and of similar organic compounds, in all possible co-solvent mixtures, is very important for scientists involved in several development stages such as substances purification and design of homogeneous liquid medicines [5]. *Address correspondence to this author at the Grupo de Investigaciones Farmacéutico Fisicoquímicas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Cra. 30 No. 45-03, Bogotá D.C., Colombia; Tel: 571-3165000-14608; Fax: 571-3165050; E-mail: fmartinezr@unal.edu.co Co-solvency has been employed in pharmacy as a solubilizing method in order to design homogeneous pharmaceutical liquid dosage forms during a long time [5-7]. In this way, two researches have been carried out to evaluate the thermodynamic effect of mixtures composition and temperature on the solubility of daidzein in ethanol + water and propylene glycol + water mixtures [8, 9]. It is important to note that ethanol and propylene glycol are the most widely used co- solvents to design and develop liquid pharmaceutical products [10]; besides, they are also used as additives in several kinds of industrial foods [11]. Furthermore, they are considered as environmentally benign solvents, useful for the purification procedures of several food components [12, 13]. Nevertheless, the preferential solvation of daidzein by the solvents in the respective mixtures i.e. the co-solvent specific composition around the daidzein molecules, has not been studied. This knowledge would lead to a better understanding of the molecular phenomena occurring during the solution processes. In this way, the inverse Kirkwood-Buff integrals (IKBI) are an efficient technique for analyzing the preferential solvation of non-electrolyte compounds in co-solvent mixtures, describing the local compositions around the solute, by the components present in the