X-Panding Halogen Bonding Interactions: Hybrid Cocrystals Composed of Ionic Halides, Iodine and Organoiodines

Halogen bonding referred to as an attractive, noncovalent interaction between an electrophilic region of a halogen atom X (acts as Lewis acid) and a nucleophilic region of a molecule Y (acts as Lewis base). Such interactions and the resulting polymeric networks play an important role in many fields related to crystal engineering, including for example, the fabrication of liquid crystals and novel drug design. The application of halogen bonding has particular promise in biological systems by increasing the lipophilicity of drugs to improve penetration through lipid membranes and tissues, enabling better intracellular delivery. Based on this concept, my research at Clemson University included the synthesis and characterization of many cocrystals derived from different alkyl/aryl ammonium/phosphonium iodides, an additional iodine source and neutral organohalogen compounds to establish versatile halogen bonding networks. Iodide salts such as PPh3MeI, NMe3PhI, (Me)4NI, (Et)4NI, 2-chloro-1-methylpyridinium iodide, 3-methylbenzothiazolium iodide, trimethylbenzylammonium iodide, tributylbenzylammonium iodide etc., an additional iodine source such as I2, iodoform etc., and several neutral organoiodines such as 1,2- or 1,4-diiodotetraflurobenzene, tetraiodoethylene, etc. have been used to synthesize salt-solvate cocrystals, where iodide or triiodide anions couple with the organic cation to form the salt component, and the neutral organiodine molecule can act as a “solvating” species. The anions and organoiodine molecules then form robust and varied halogen bonding networks, while the cations can also influence the structure based on their size, and their participation in complementary intermolecular interactions such as phenyl embraces, pi-pi interactions, and CH-pi interactions. For example, triphenylmethyl phosphonium iodide reacts with iodine and tetraiodoethylene to form triphenylmethylphosphonium triiodide cocrystal with tetraiodoethylene both by a simple mechanochemical synthesis (grinding the components together) and by solution chemistry (slow evaporation) in a variety of solvents. By varying the reaction stoichiometry, temperature, and solvent type, a robust crystal chemistry has been revealed. The resulting halogen bonding networks exhibit different chains, layers, or three-dimensional networks and broadened the scope and potential applications of halide crystal engineering. Additionally, several polyiodide salts have been synthesized by varying the reaction stoichiometry of iodide salts and the source of iodine used. The resulting polyiodide networks also exhibit different chains, layers, or three-dimensional networks based on the halogen bonding interactions formed. This study helps to understand the structural nature of higher polyiodides on a fundamental level and provides new insights into the classification of such polyiodides within the continuum of covalent and halogen bonding interactions. Moreover, some iodide cocrystals with organoiodine compounds have also been synthesized and their halogen bonding networks have been investigated and further compared with that in triiodide cocrystals having the same cation. This study helps to better understand the directional (or, non-directional) nature of the anions in establishing the halogen bonding motifs and provides an additional tool to apply to problems in crystal engineering. Finally, presence of other intermolecular noncovalent interactions such as phenyl embracing, pi-pi stacking, CH-pi interactions, F-pi interactions and hydrogen bonding have been studied for all the cocrystals