Dynamic processes have many implications in functional molecules, including catalysts, enzymes, host-guest complexes, and molecular machines. Here, we demonstrate via deuterium NMR relaxation experiments how halogen bonding directly impacts the dynamics in solid 2,3,5,6-tetramethylpyrazine cocrystals, catalyzing the methyl group rotation. On average, we observe a reduction of 56% in the rotational activation energy of the methyl groups in the halogen bonded cocrystals, contrasting the reduction of 36% in the hydrogen bonded cocrystals, with respect to pure 2,3,5,6-tetramethylpyrazine. Density functional theory calculations attribute this superior catalytic ability of the halogen bond to the simultaneous destabilization of the staggered conformation and stabilization of the gauche conformation, overall reducing the rotational energy barrier. Furthermore, the calculations suggest that the catalytic ability of the halogen bond may be tuneable, with stronger halogen bond donors acting as superior dynamics catalysts. Thus, halogen bonding may play a role in both assembly and promoting dynamical processes.

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Halogen bonding is a noncovalent interaction between the electrophilic region of a halogen (σ-hole) and an electron donor, which has gained popularity in the field of crystal engineering due to its strength and linearity. Here, we present a 35Cl solid-state NMR study of chlorine atoms as halogen bond donors, with interpretation aided by crystallographic symmetry and computational chemistry. In a series of chlorinated benzonitrile compounds, the magnitude of the 35Cl quadrupolar coupling constant (C Q) was found to increase, and the quadrupolar asymmetry parameter (η) was found to decrease upon halogen bonding. A natural localized molecular orbital (NLMO) analysis attributes these changes to an increase in the contribution from the lone pair NLMOs to |C Q|. This is distinguished from a short proton-chlorine contact, which causes an increase in the magnitude of the σ-bond contribution and a decrease in the lone pair contribution, resulting in an overall decrease in |C Q|. This first direct 35Cl solid-state NMR study of chlorine as a halogen bond donor provides new physical insight into the relationship between NMR observables and the halogen bond.

Several synthetic techniques are available for the preparation of halogen-bonded adducts, including traditional solvent-evaporation methods and mechanochemistry. With the intention of reducing solvent usage and experimental times, we establish cosublimation as a synthetic technique for preparing halogen-bonded cocrystals, focusing on the C–I···N motif involving nitrogen-containing heterocycles. We selected four common halogen-bond donors (I2, 1,4-diiodobenzene, 1,4-diiodotetrafluorobenzene, 1,3,5-trifluoro-2,4,6-triiodobenzene) and four halogen-bond acceptors (2,3,5,6-tetramethylpyrazine, 1,4-diazabicyclo[2.2.2]­octane, 2,2′-bipyridyl, 1-adamantanecarbonitrile), by virtue of their range in volatility, and explored all 16 combinations via the following methods: solvent evaporation, overnight cosublimation in a sealed glass tube using a two-zone furnace, and expedited cosublimation in a vacuum sublimation apparatus. We show that the raw crystals obtained from overnight cosublimation are of suitable quality for single-crystal X-ray diffraction, resulting in five new crystal structures, two of which are, currently, unobtainable through other methods. Of these new structures, the first halogen bond to the nitrile group of 1-adamantanecarbonitrile is reported, resulting in the formation of a supramolecular rotor in a spinning top configuration as evidenced by 13C and 15N solid-state NMR spectroscopy. Strikingly, the cosublimation approach overcomes an anticooperative halogen-bonding effect to produce fully saturated cocrystals of the tritopic halogen bond donor 1,3,5-trifluoro-2,4,6-triiodobenzene with 1,4-diazabicyclo[2.2.2]­octane. Finally, we show that cosublimation can be used to rapidly prepare and purify bulk samples using a vacuum sublimation apparatus, enabling the scalable preparation of halogen-bonded cocrystals within 10 to 30 min using common laboratory equipment. The methods described here enable a broad exploration of the polymorphic landscape and may be extended to the facile preparation of other classes of cocrystals.

This Highlight article discusses the role of solid-state NMR spectroscopy in crystal engineering with the aid of several examples from the literature.

Halogen bonding is a noncovalent interaction between the electrophilic region of a halogen (σ-hole) and an electron donor. We report a crystallographic and structural analysis of halogen-bonded compounds by applying a combined X-ray diffraction (XRD) and solid-state nuclear magnetic resonance (SSNMR) approach. Single-crystal XRD was first used to characterize the halogen-bonded cocrystals formed between two fluorinated halogen-bond donors (1,4-diiodotetrafluorobenzene and 1,3,5-trifluoro-2,4,6-triiodobenzene) and several nitrogen-containing heterocycles (acridine, 1,10-phenanthroline, 2,3,5,6-tetramethylpyrazine, and hexamethylenetetramine). New structures are reported for the following three cocrystals, all in the P2/c space group: acridine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), CFI·CHN, 1,10-phenanthroline-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), CFI·CHN, and 2,3,5,6-tetramethylpyrazine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), CFI·CHN. C andF solid-state magic-angle spinning (MAS) NMR is shown to be a convenient method to characterize the structural features of the halogen-bond donor and acceptor, with chemical shifts attributable to cocrystal formation observed in the spectra of both nuclides. Cross polarization (CP) from F toC results in improved spectral sensitivity in characterizing the perfluorinated halogen-bond donor when compared to conventional H CP. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of magnetic shielding constants, along with optimization of the XRD structures, provide a final set of structures in best agreement with the experimentalC and F chemical shifts. Data for carbons bonded to iodine remain outliers due to well-known relativistic effects.

Halogen-bonded and hydrogen-bonded cocrystals of 3-iodoethynylbenzoic acid and several nitrogen-containing heterocycles are formed using mechanochemical and solvent-based slow evaporation methods.

Halogen bonds drive the self-assembly of 2-iodoethynylpyridine and 2- iodoethynyl-1-methyl-imidazole into discrete supramolecular triangles.