Perhalogenated Anilines as Bifunctional Donors of Hydrogen and Halogen Bonds in Cocrystals with Ditopic Nitrogen-Containing Acceptors.

In this study, we examine the experimental and theoretical capabilities of two perhalogenated anilines, 2,3,5,6-tetrafluoro-4-bromoaniline (btfa) and 2,3,5,6-tetrafluoro-4-iodoaniline (itfa) as hydrogen and halogen bond donors. A series of 11 cocrystals derived from the two anilines and selected ditopic nitrogen-containing acceptors (4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane, and 1,4-diazabicyclo[2.2.2]octane) in 1:1 and 2:1 stoichiometries were prepared by liquid-assisted grinding and crystallization from solution. Crystallographic analysis revealed bifunctional donor properties in both anilines. The dominant supramolecular interaction in four cocrystals of btfa is the N-H···Nacceptor hydrogen bond between btfa and acceptor molecules, while in the one remaining cocrystal, donor and acceptor molecules are connected via the N-H···Nacceptor hydrogen bond and the Br···Nacceptor halogen bond. In two cocrystals of itfa, the dominant supramolecular interaction is the I···Nacceptor halogen bond between itfa and acceptor molecules, while in the remaining four cocrystals, donor and acceptor molecules are additionally connected by the N-H···Nacceptor hydrogen bond. Periodic density-functional theory (DFT) calculations have been conducted to assess the formation energies of these cocrystals and the strengths of the established halogen and hydrogen bonds. Molecular DFT calculations on btfa and itfa indicate that the differences in electrostatic potential between the competing sites on the molecules are 261.6 and 157.0 kJ mol-1 e-1, respectively. The findings suggest that itfa, with a smaller electrostatic potential difference between donor sites, is more predisposed to act as a bifunctional donor.

Elucidating mechanochemical reactivity of a ternary halogen-bonded cocrystal system by computational and calorimetric studies.

Discovery of a halogen-bonded ternary cocrystal of 1,3,5-trifluoro-2,4,6-triiodobenzene with pyrazine and triphenylphosphine sulfide has revealed a complex landscape of multicomponent phases, all achievable by mechanochemical interconversion. The observed solid-state reaction pathways were explained by periodic density-functional calculations and comprehensive intermolecular interaction analysis, supported by dissolution calorimetry measurements.

Cationcation hydrogen bonds in synephrine salts: a typical interaction in an unusual environment.

Hydrogen bonds between the same charge species have been labelled sometimes as pseudo, destabilizing or anti-electrostatic types as they fail to overcome the energetic destabilization, resulting from electrostatic repulsion between same charged species. They have also been proposed to be a result of coulombic compression caused by the attraction between counterions in the crystals. Such a hypothesis is faulty, which undermines the importance of hydrogen bonds in these cases. In this context, we report several cationcation species held together by the O-HO, N-HO and C-HO type hydrogen bonds observed in the crystalline salts of a nutraceutical compound (±)-p-synephrine. The hydrogen-bonded cationcation molecular pairs present in these salts were carefully analyzed using the quantum theory of atoms in molecules, non-covalent interaction plots, potential energy surface scans, and energy decomposition analysis. This study provides new insights into the nature and strength of the various types of hydrogen bonds present between the cationic molecular pairs and helps in delineating the role played by them in stabilizing the cationcation assembly. We also report a unique cationic dimer having water-mediated N-HO hydrogen bonds, which hold the two cationic charge centres at a very short intermolecular distance in the crystal. The analysis of the water-mediated cationic pair observed in this case revealed that the solvent can play a crucial role in reducing the coulombic repulsion between the two cations.