Thermodynamic analysis and molecular dynamic simulation of solid-liquid phase equilibrium of imazapyr in twelve pure organic solvents

In this work, we determined the solubility of imazapyr in twelve mono organic solvents by gravimetric method over the temperature ranging from 283.15 K to 323.15 K at atmospheric pressure, and the results show that the equilibrium solubility is positively correlated with temperature in all solvents. Meanwhile, Hirshfeld surface analysis and molecular electrostatic potential surface were severally employed to probe into the intermolecular interactions and the overall charge distribution of imazapyr, the estimated results indicate that H···H and O···H contacts obviously predominate among all contact interactions and imazapyr has great hydrogen bonding donor and acceptor capacities. Besides, we investigated the effects of physicochemical properties of solvents on dissolution behaviors and found that solvent polarity plays a decisive role in the solubility of imazapyr in most cases. Molecular dynamic (MD) simulations were further applied to interpret the solute-solvent interactions behind different solubility behaviors of imazapyr. Additionally, the experimental solubility values were well correlated by the modified Apelblat equation, λh equation as well as NRTL model, respectively. And all of the ARD% values are less than 3%, indicating that the three thermodynamic models all achieve the perfect fitting performance. Finally, the mixing thermodynamic properties including ∆mixG0, ∆mixH0, and ∆mixS0 were calculated based on the NRTL model. The results suggest that the mixing process is spontaneous, exothermic and entropy driven as well. The solubility of imazapyr is positively correlated with temperature. Molecular Hirshfeld surface analysis indicates that the H···H and O┄H contacts prominently dominate among all contact interactions and MEPs analysis suggests that imazapyr holds great hydrogen bonding donor/acceptor capacities, indicating that strong hydrogen bonding interactions can be formed between imazapyr and polar solvents. RDF analysis further reveals that hydrogen bonding interactions is the decisive factor for the highest solubility of imazapyr in methanol. [Display omitted] •Solubility of imazapyr was measured by gravimetric method in twelve pure organic solvents.•Molecular dynamic simulations were used to probe into the interaction of solute-solvent.•Three thermodynamic models were provided to correlate the solubility of imazapyr.