Evaluation of Concomitant Halogen and Pnictogen Bonds in Cocrystals of Imines Derived from 2-Nitrobenzaldehyde and 4-Haloaniline.

Three imines have been prepared by condensation of 2-nitrobenzaldehyde and 4-haloanilines (halo = Cl, Br, and I) with functionalities that enabled them to act as both halogen and pnictogen bond donors; however, both interactions were found to be absent in the solid state. The prepared imines were further cocrystallized with 1,3-diiodotetrafluorobenzene and 1,3,5-triiodotetrafluorobenzene as halogen bond donors. Six novel cocrystals were prepared by means of liquid-assisted mechanochemical synthesis and by crystallization from solution. All six cocrystals were of 1:1 stoichiometry and comprised a N···I halogen bond between an iodine atom of the perhalogenated halogen bond donor and the imino nitrogen atom of the imine acting as an acceptor. Additionally, in all six cocrystals, the imine molecules were interconnected by NO2···NO2 pnictogen bonding interactions. Computational analysis has shown that the NO2···NO2 exhibits bond critical point electron densities in the region (4.897-8.306) × 10-3 e Å-3 and interaction energies of 23.6-27.7 kJ mol-1, whereas the N···I halogen bonds generally have higher critical point electron densities ((1.795-1.937) × 10-2 e Å-3), but the corresponding total interaction energies are lower (19.4-20.4 kJ mol-1). Statistical analysis of the appearance of NO2···NO2 contacts concomitantly with halogen or hydrogen bonds seems to indicate that there is a positive correlation between the presence of NO2···NO2 pnictogen bonding interactions and other directional interactions in crystal structures.

2,2'-Bipyridine Derivatives as Halogen Bond Acceptors in Multicomponent Crystals.

In this work, we present a systematic study of the halogen bonding potential of different 2,2'-bipyridine derivatives in the synthesis of cocrystals by using selected perfluorinated iodobenzenes and N-haloimides as halogen bond donors. These halogen bond acceptor molecules were chosen to explore how different substituents on 2,2'-bipyridine affect halogen bond formation. Out of 24 combinations, we obtained only 8 cocrystals by using two methods, liquid-assisted grinding and crystallization from the solution. Of those 8 cocrystals, one has already been described in the literature. As expected, structural data revealed that 2,2'-bipyridine derivatives act as ditopic halogen bond acceptors in all structures. Dominant interactions in 7 of the cocrystals are I···N or Br···N halogen bonds, while in the one remaining cocrystal it is the I···C(π) halogen bond.

Keggin-Type Anions as Halogen Bond Acceptors.

To study the potential of Keggin-type polyoxometalate anions to act as halogen bond acceptors, we have prepared a series of 10 halogen-bonded compounds starting from phosphomolybdic and phosphotungstic acid and halogenopyridinium cations as halogen (and hydrogen) bond donors. In all the structures, the cations and the anions were interconnected by halogen bonds, more often with terminal M=O oxygen atoms than with bridging oxygen atoms as acceptors. In four structures comprising protonated iodopyridinium cations capable of forming both hydrogen and halogen bonds with the anion, the halogen bond with the anion is apparently favored, whereas hydrogen bonds preferentially involve other acceptors present in the structure. In three obtained structures derived from phosphomolybdic acid, the corresponding oxoanion has been found in its reduced state [Mo12PO40]4-, which has also led to a decrease in halogen bond lengths as compared to the fully oxidated [Mo12PO40]3-. The electrostatic potential on the three types of anions involved in the study ([Mo12PO40]3-, [Mo12PO40]4-, and [W12PO40]3-) has been calculated for optimized geometries of the anions, and it has been shown that the terminal M=O oxygen atoms are the least negative sites of the anions, indicating that they act as halogen bond acceptors primarily due to their steric availability.

Halogen Bond Motifs in Cocrystals of N,N,O and N,O,O Acceptors Derived from Diketones and Containing a Morpholine or Piperazine Moiety.

In this study, we investigate the halogen bond acceptor potential of oxygen and nitrogen atoms of morpholine and piperazine fragments when they are peripherally located on N,O,O or N,N,O acceptor molecules. We synthesized four acceptor molecules derived from either acetylacetone or benzoylacetone and cocrystallized them with 1,4-diiodotetrafluorobenzene and 1,3,5-triiodotrifluorobenzene. This resulted in eight cocrystals featuring different topicities and geometric dispositions of donor atoms. In all cocrystals, halogen bonds are formed with either the morpholinyl oxygen atom or the terminal piperazine nitrogen atom. The I···Omorpholine halogen bonds feature lower relative shortening values than I···Nterminal, I···Ocarbonyl, and I···Nproximal halogen bonds. The N and O halogen bond acceptor sites were evaluated through calculations of molecular electrostatic potential values.

Anticooperativity of Multiple Halogen Bonds and Its Effect on Stoichiometry of Cocrystals of Perfluorinated Iodobenzenes.

To investigate influences on the topicity of perfluorinated halobenzenes as halogen bond (XB) donors in the solid state, we have conducted a database survey and prepared 18 novel cocrystals of potentially ditopic (13ditfb, 14ditfb) and tritopic (135titfb) XB donors with 15 monotopic pyridines. 135titfb shows high tendency to be mono- or ditopic, but with strong bases it can act as a tritopic XB donor. DFT calculations have shown that binding of a single acceptor molecule on one of the iodine atoms of the XB donor reduces the ESPmax on the remaining iodine atoms and dramatically decreases their potential for forming further halogen bonds, which explains both the high occurrence of crystal structures where the donors do not achieve their maximal topicity and the observed differences in halogen bond lengths. Despite the fact that this effect increases with the basicity of the acceptor, when the increase of halogen bond energy due to the basicity of the acceptor compensates its decrease due to the reduction of the acidity of the donor, it enables strong bases to form cocrystals in which a potentially polytopic XB donor achieves its maximal topicity.

Isostructural Halogen Exchange and Halogen Bonds: The Case of N-(4-Halogenobenzyl)-3-halogenopyridinium Halogenides.

Six N-(4-halogenobenzyl)-3-halogenopyridinium cations were prepared by reacting meta-halogenopyridines (Cl, Br, and I) with (4-halogenobenzyl) bromides (Br and I) and were isolated as bromide salts, which were further used to obtain iodides and chlorides. Sixteen compounds (out of 18 possible cation/anion combinations) were obtained; two crystallized as hydrates and 14 as solvent free salts, 11 of which belonged to one isostructural series and 3 to another. All crystal structures comprise halogen-bonded chains, with the anion as an acceptor of two halogen bonds, with the pyridine and the benzyl halogen substituents of two neighboring cations. The halogen bonds with the pyridine halogen show a linear correlation between the relative halogen bond length and angle, which primarily depend on the donor halogen. The parameters of the other halogen bonds vary with all three halogens, indicating that the former halogen bond is the dominant interaction. This is also in accord with the calculated electrostatic potential in the σ-holes of the halogens and the thermal properties of the solids. The second isostructural group comprises combinations of the best halogen bond donors and acceptors, and features a more favorable halogen bond geometry of the dominant halogen bond, reaffirming its significance as the main factor in determining the structure.

Conservation of the Hydrogen-Bonded Pyridone Homosynthon in Halogen-Bonded Cocrystals.

Seven cocrystals of pyridone and perfluorinated halocarbons have been prepared. In all cases pairs of pyridone molecules are connected into dimers by two N-H···O hydrogen bonds, forming the characteristic pyridone homosynthon of R2 2(8) topology. These dimers further act as acceptors of halogen bonds through the two pyridone oxygen atoms, forming two (in six cases) or three (in one case) halogen bonds with the donor molecules. The stoichiometry of the cocrystals obtained and the overall topology of the supramolecular architecture depend primarily on the topicity of the halogen bond donor, with the monotopic donor yielding a cocrystal of 1:1 stoichiometry comprising discrete supramolecular complexes, the ditopic donors cocrystals of 1:2 stoichiometry comprising chains, and the tritopic donor a cocrystal of 1:2 stoichiometry comprising hydrogen- and halogen-bonded layers. The results indicate that the pyridone homosynthon is a robust and reliable supramolecular synthon that is conserved in halogen-bonded cocrystals of pyridone.

Evaluation of Halogenopyridinium Cations as Halogen Bond Donors.

We have performed a database survey and a structural and computational study of the potential and the limitations of halogenopyridinium cations as halogen bond donors. The database survey demonstrated that adding a positive charge on a halogenopyridine ring increases the probability that the halogen atom will participate in a halogen bond, although for chloropyridines it remains below 60%. Crystal structures of both protonated and N-methylated monohalogenated pyridinium cations revealed that the iodo- and bromopyridinium cations always form halogen-bonding contacts with the iodide anions shorter than the sum of the vdW radii, while chloropyridinium cations mostly participate in longer contacts or fail to form halogen bonds. Although a DFT study of the electrostatic potential has shown that both protonation and N-methylation of halogenopyridines leads to a considerable increase in the ESP of the halogen σ-hole, it is generally not the most positive site on the cation, allowing for alternate binding sites.

Cobaloximes as Building Blocks in Halogen-Bonded Cocrystals.

In this work, we explore the halogen-bonded cocrystallization potential of cobaloxime complexes in the synthesis of cocrystals with perhalogenated benzenes. We demonstrate a strategy for synthesizing halogen-bonded metal-organic cocrystals by utilizing cobaloximes whose pendant bromide group and oxime oxygen enable halogen bonding. By combining three well-known halogen bond donor molecules differing in binding geometry and composition with three cobaloxime units, we obtained a total of four previously unreported cocrystals. Single crystal X-ray diffraction experiments showed that the majority of obtained cocrystals exhibited the formation of the targeted I···O and I···Br motives. These results illustrate the potential of cobaloximes as halogen bond acceptors and indicate that this type of halogen bond acceptors may offer a novel route to metal-organic halogen-bonded cocrystals.