Difenoconazole solubility in acetonitrile/N,N-dimethylformamide/acetone + water and quantum chemistry study into inter/intra-molecular interactions

Abstract

The difenoconazole solubilities in acetonitrile/acetone/N,N-dimethylformamide (DMF) + water systems were acquired experimentally with the help of the isothermal shake-flask technique. Analysis of X-ray power diffraction revealed that difenoconazole did not exhibit any crystal transition as well as solvate formation. The solubility acquired here was accurately correlated, which yielded relative average deviations (RAD) of ≤4.99 % and a root-mean-square deviation of ≤20.59 × 10⁻⁵ through the Jouyban-Acree and modified van’t Hoff-Jouyban-Acree models Additionally, to explain the solubility behavior at a temperature of 298.15 K, this work examines the acetonitrile/acetone/DMF + water and the previously published methanol/ethanol/isopropanol/PG + water blends utilizing the extended Hildebrand solubility technique. The RAD levels remained below 6.88 %. The dipolarity-polarizability and the solubility parameter of blended solvents exert a substantial impact on the variability of difenoconazole solubility. The preferred solvation of difenoconazole at a temperature of 298.15 K was examined through the inverse Kirkwood-Buff integrals. The solvation parameters’ values of difenoconazole were positive in blends containing methanol, acetone, DMF, ethanol, isopropanol, and acetonitrile with moderate and rich compositions. This indicates that difenoconazole is preferentially solvated by them in above composition ranges. A shift from an enthalpy-driven mechanism to an entropy-driven one was revealed through an analysis of the thermodynamics of the entropy-enthalpy relationship in the dissolution of difenoconazole in blends. Furthermore, the mean local ionization energy, Hirshfeld surface as well as molecular surface electrostatic potential were employed to illustrate the microscopic electrostatic characteristics. The N and N groups in the five-membered ring of difenoconazole molecule are the primary sites for electrophilic attack. The weak contacts of difenoconazole-solvent were demonstrated with the help of a Hirshfeld partition analysis-based independent gradient model.