Tuning Supramolecular Structure in Trimethylglycine Cocrystals: Competition Between Hydrogen and Halogen Bonding upon Cl/Br Substitution

Two novel cocrystals of zwitterionic trimethylglycine (TMG) with 2,6-dichlorophenol [TMG•2,6-dichlorophenol] (1:1) and 2,6-dibromophenol [TMG•2,6-dibromophenol] (1:2) are synthesized and structurally characterized using single crystal X-ray diffraction. To estimate the energy of various intermolecular interactions, periodic DFT calculations were performed followed by Bader analysis of the crystalline electron density. TMG molecules form dimers in [TMG•2,6-dichlorophenol] (1:1). Its supramolecular structure is governed by the primary charge-assisted H-bonds (~60 kJ/mol) and supported by C-H∙∙∙O contacts (~12 kJ/mol). Cl/Br substitution introduces a more potent halogen-bonding donor. The Br∙∙∙O^- interaction (~10 kJ/mol) is strong enough to reorganize the packing into a catemeric motif. As a result, TMG molecules form infinite chains in [TMG•2,6-dibromophenol] (1:2). This illustrates that "fine tuning" is not merely about changing distances, but about shifting the entire energy hierarchy of the crystal. Two-dimensional fingerprint diagrams (2D diagrams) obtained from the Hirshfeld surface and Bader's analysis of the crystalline electron density give significantly different values of the contributions of the H∙∙∙H contacts, 28% vs. 5% respectively. The main reason for this discrepancy is the large number of relatively short intermolecular H∙∙∙H contacts without a critical bond point in trimethylglycine cocrystals.