Solubilityand Solution Thermodynamics of Novel BicyclicDerivatives of 1,3-Selenazine in Biological Relevant Solvents.

Drug-likeN-substituted 1-selena-3-azaspiro[5,5]undec-2-en-2-aminehydrobromides (1:1) have been synthesized. Phenyl, isopropylphenyl,and fluorophenyl substituents were used. The solubility of the obtainedcompounds in pharmaceutically relevant solvents within the temperaturerange from (298.15 to 318.15) K has been measured using the isothermalsaturation technique. All of the compounds studied appear to havepoor solubility of ∼10–6mole fraction inphosphate buffer pH 7.4 and hexane. The solubility values enlargesubstantially to ∼10–2and 10–4mole fraction, respectively, in octanol and muriatic buffer solutionpH 2.0. The solubility of the selenazines in aqueous media was shownto increase as the number of protonated forms grew. The high solubilityof the compounds in octanol was found to depend on the formation ofintermolecular solvent–solute hydrogen bonds. Thermodynamicsolubility functions for the substances in the solvents studied havebeen calculated. The solubility in all of the systems with the predominantenthalpy term of Gibbs energy was proved to increase as the dissolutionenthalpy decreased. [ABSTRACT FROM AUTHOR]