Thermodynamics of transfer and partition of 3,5-diamino-1-phenyl-1,2,4-triazole in the 1-octanol/water biphasic system

In this paper, we focus for the first time on thermodynamics of transfer of 3,5-diamino-1-phenyl-1,2,4-triazole (DAPT) from water to liquid 1-octanol which is considered in pharmaceutical chemistry as an appropriate model of a lipid-like environment for studying a passive membrane transport of various drugs. The enthalpies of solution of DAPT have been determined calorimetrically in both solvents at 298.15, 308.15 and 328.15 K. The partition coefficients (P) have been obtained in the 1-octanol/water biphasic system at 298.15 and 328.15 K using a classical isothermic saturation method. Standard thermodynamic functions of DAPT transfer from water to a lipid-like phase have been calculated via the Gibbs–Helmholtz equation using the temperature dependence of the standard enthalpies of solution and the partition coefficient at the reference temperature of 298.15 K. We have found that the enthalpic term favours the solute transfer both at lower and elevated temperatures, whereas the entropic one contributes in the opposite manner. The free energy of transfer remains negative for all the temperature range studied indicating rather appreciable affinity of a potential drug towards a lipid-like environment. The comparison of the experimental and calculated P values indicates that our approach is able to predict with a good accuracy the behaviour of the 1,2,4-triazole derivatives for the physiological temperature range.