Journal of Chemical and Engineering Data, Vol.59, No.7, 2298-2304, 2014
Solubility and Solution Thermodynamics of Novel Bicyclic Derivatives of 1,3-Selenazine in Biological Relevant Solvents
Drug-like N-substituted 1-selena-3-azaspiro[5,5]undec-2-en-2-amine hydrobromides (1:1) have been synthesized. Phenyl, isopropylphenyl, and fluorophenyl substituents were used. The solubility of the obtained compounds in pharmaceutically relevant solvents within the temperature range from (298.15 to 318.15) K has been measured using the isothermal saturation technique. All of the compounds studied appear to have poor solubility of similar to 10(-6) mole fraction in phosphate buffer pH 7.4 and hexane. The solubility values enlarge substantially to similar to 10(-2) and 10(-4) mole fraction, respectively, in octanol and muriatic buffer solution pH 2.0. The solubility of the selenazines in aqueous media was shown to increase as the number of protonated forms grew. The high solubility of the compounds in octanol was found to depend on the formation of intermolecular solvent solute hydrogen bonds. Thermodynamic solubility functions for the substances in the solvents studied have been calculated. The solubility in all of the systems with the predominant enthalpy term of Gibbs energy was proved to increase as the dissolution enthalpy decreased.