On the Rationalization of Formation of Solvates: Experimental and Computational Study of Solid Forms of Several Nitrobenzoic Acid Derivatives
Agris Be̅rziņš, Artis Kons, Kristaps Saršu̅ns, Sergey Belyakov, Andris Actiņš
Abstract
Analysis of crystal structures, molecular properties, interaction strength in solution, and computationally generated nonsolvated form crystal structure landscapes of five chloronitrobenzoic acid isomers and two additional 2-substituted 4-nitrobenzoic acids were used to rationalize the obtained solvate landscape of these compounds. Screening of the solid forms was performed for each of the compounds, and crystal structures of the obtained nonsolvated forms and selected solvates were determined. Molecular conformation, intermolecular interactions, and packing efficiency of nonsolvated forms and solvates were analyzed to understand factors contributing to structure stabilization and determining the formation of the observed crystal structures. Computationally generated crystal structure landscapes of nonsolvated forms were tested for the possibility to predict the propensity to form solvates and identify polymorphic compounds. It was observed that most of the solvates were obtained with solvents acting as strong hydrogen bond acceptors and/or able to form aromatic interactions. Solute–solvent association Gibbs energy representing interaction strength was found to be the most apparent identifiable factor explaining the solvate formation of the studied compounds, and using this tool, the existence of 3 new multicomponent phases was successfully predicted.