Mechanistic Study on Interface Interactions and Its\nEffect on Crystal GrowthA Case of Cloxacillin Sodium Monohydrate

Solvents\nare essential factors in influencing the morphology of\nsubstances that crystallize from the solution. In this study, a combined\napproach involving molecular dynamics simulations and experimental\ninvestigations was employed to investigate the impact of various solvent\nsystems on the crystal morphology of cloxacillin sodium monohydrate.\nThe crystal morphology of cloxacillin sodium monohydrate was predicated\nusing the modified attachment energy model, and it was verified by\nexperiments within seven binary solvent systems (methanol + butyl\nacetate, methanol + acetone, methanol + acetonitrile, methanol + isopropyl\nalcohol, water + acetone, water + acetonitrile, and water + isopropanol).\nFurthermore, a strong correlation between the binding energies of\nsolvents with the (1 0 1) and (0 1 1) crystal planes and their respective\ngrowth rates was revealed. Structural analyses of the three principal\ncrystal faces revealed that the roughness and electrostatic potential\n(ESP) distribution of the crystal planes can affect the interactions\nbetween the crystal planes and solvents to varying degrees. Strong\ninteractions between the solvent and crystal planes promoted solvent\nadsorption, impeding the adsorption of solute molecules and thus reducing\nthe growth rate of the crystal planes. Additionally, radial distribution\nfunction analysis further verified the interactions between solvents\nand crystal planes, indicating that these interactions were primarily\ngoverned by van der Waals forces and Coulombic forces.