Conformational Change in Molecular Crystals: Impact of Solvate Formation and Importance of Conformational Free Energies

Changes in molecular conformation and its relationship with crystal polymorphism have been well documented previous work. To the best of our knowledge, however, effect solvate formation on has never explored. Using Cambridge Structural Database combination modeling, we provide insights into impact adopted by a compound whether such is different to that found neat form(s). Typically, more flexible molecule is, higher chances conformational change occurs upon formation. There are no trends as relative stability conformers their likelihood be observed either solvates or forms. conformer energy differences solvate-neat form pairs small (<5 kJ/mol) when larger (>15 kJ/mol), these can reduced significantly both solvent thermal effects considered simulations. This highlights importance computing contributions energies accounting for environmental effects. Overall, find mirrors behavior polymorphism.