Conformational flexibility and hydrogen-bonding patterns of the neotame molecule in its various solid forms

The conformational flexibility and the molecular packing patterns of the neotame molecule in its various crystal forms, including neotame monohydrate, methanol solvate, ethanol solvate, benzene solvate, and anhydrate polymorph G, are analyzed in this work. The Cerius2 molecular modeling program with the Dreiding 2.21 force field was employed to calculate the most stable conformations of neotame molecules in the gaseous state and to analyze the conformations of the neotame molecule in its various crystal forms. Using graph set analysis, the hydrogen bond patterns of these crystal forms were compared. The neotame molecule takes different conformations in its crystal forms and in the free gaseous state. Cerius2 found 10 conformers with lower conformational energies than those in the actual crystal structures, which represent an energetic compromise. The relatively large differences between the energies of the conformers indicate the necessity for rewriting or customizing the force field for neotame. The hydrogen bonding patterns of the neotame methanol and ethanol solvates are identical, but different from those of the other three forms, which also differ from each other. The neotame molecule in its various crystal forms takes different conformations that differ from those in the gaseous state because of the influence of crystal packing. The intramolecular ring, S5, is present in all the crystal forms. The following hydrogen bonding patterns occur in some of the crystal forms: diad, D; intramolecular rings, S(6) and S(7); chains, C(5) and C(6); and an intermolecular ring, R2(2)(12).