Thermodynamic insights to solubility and lipophilicity of new bioactive hybrids triazole with thiazolopyrimidines

• Published in: Journal of molecular liquids 2021-02, Vol.324, p.114662, Article 114662
• Main Authors: Blokhina, Svetlana V., Ol'khovich, Marina V., Sharapova, Angelica V., Levshin, Igor B., Perlovich, German L.
• Format: Article
• Language: English
• Subjects: Hansen solubility parameter; Novel bioactive compounds; Partition coefficient; Solubility; Thermodynamics
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2020.114662

Four novel potential antifungal 1,2,4-triazole hybrids of thiazolopyrimidines with different - methyl-, methoxy-, chloro-, and fluoro- substituents in the molecule phenyl ring were synthesized and characterized by 1H NMR spectra. The PXRD and DSC techniques showed that the solid phases of the obtained compounds were amorphous. The kinetic solubility of the substances was studied in aqueous media of various acidity degrees. The equilibrium solubility of the derivatives was determined in buffers (pH 2.0 and 7.4) and 1-octanol at (293.15–313.15) K by the shake flask method. The compound solubility in the buffers did not exceed 9.0∙10−4 mol/L and decreased when the substituent was changed as follows: methoxy-, methyl-, chloro-, and fluoro-. The methoxy-derivative was found to have the more higher solubility in 1-octanol - 1.3∙10−2 mol∙L−1 at 298.15 K. The solubility behavior of the substances was studied based on Hansen solubility parameters. The solubility values were correlated by the modified van't Hoff and modified Apelblat equations. The best result was achieved with the modified Apelblat model. The partition coefficients of the compounds in the 1-octanol/buffer pH 7.4 system were determined at (293.15–313.15) K. The logPO/B values of the substances ranged from 0.80 to 1.27 at 298.15 K, depending on the chemical nature of the substituents that indicates to good balance between their solubility and permeability. The thermodynamic functions of dissolution and partition for the compounds studied in the solvents selected were calculated. A diagram approach was used to analyze the enthalpy and entropy contributions to the Gibbs energy of dissolution of the substances studied. •Solubility of four new bioactive compounds in 1-octanol, buffers (pH 2.0 and 7.4).•Correlations by the van't Hoff and modified Apelblat equations for solubility data.•Partition coefficients of compounds studied in 1-octanol/buffer pH 7.4 system.•Combination Hansen solubility parameter with solubility behavior.•Thermodynamic functions of dissolution and partition in model solvents.