Discovery of a polymorph of tris(p-tolyl)antimony(III) reveals solid-state supramolecular dimers connected through short, attractive Sb∙∙∙Sb contacts that, based on theoretical calculations and a systematic screen of the Cambridge Structural Database (CSD), could be an overlooked hallmark of the solid-state and supramolecular chemistry of trivalent organoantimony(III) compounds. While the previously reported crystal structure of tris(p-tolyl)antimony(III) is known to exhibit phenyl embrace motifs, resembling the arsenic or phosphorus analogs, the new polymorph exhibits supramolecular dimers characterized by direct Sb∙∙∙Sb contacts shorter than the sum of the van der Waals radii, and stabilized by a significant dimer dissociation energy of ca. -26 kJ mol-1 established by periodic density-functional calculations. Theoretical analysis indicates that the contacts are attractive and dispersion-dominated, with an overview of the CSD showing that such direct Sb···Sb contacts are not unique to this polymorphic form of tris(p-tolyl)antimony(III) but appear to be a more general feature of trivalent organoantimony in the solid state. Specifically, the CSD shows that dimers based on short Sb···Sb contacts are found across a number of organoantimony structures, including some of the simplest representatives of the series, such as triphenyl- and trimethylantimony, for which the dimer interaction energy is herein calculated to be ca. -13 kJ mol-1.

A proof-of-principle study is outlined for the construction of multicomponent metal-containing solids, i.e. three- and four component metal-organic halogen-bonded cocrystals (MOXB) based exclusively on I⋯S halogen bonds. This research represents a curiosity-driven exploration that yielded highly significant observations regarding the ability of the metal-organic multitopic acceptor to simultaneously engage in halogen bonding with a large number of halogen bond donors (up to five) due to the presence of an acceptor species, the isothiocyanate sulfur atom, which forms a robust I⋯SCN synthon. The effectiveness of this exploration is proven by the synthesis of a unique family of four ternary and one quaternary cocrystal using a Ni(ii) coordination compound, Ni(4-methylpyridine)4(NCS)2, and three perfluorinated iodobenzenes. All cocrystals were obtained as crystallization products from a solution of three (or four) reactants. Periodic density-functional theory calculations have been conducted to assess the formation energies of the obtained cocrystals and the strengths of the established intermolecular interactions. The presented research indicates significant potential of MOXB cocrystals in the efficient synthesis of higher-order cocrystals based solely on halogen bonds and could serve as the basis for an approach to designing higher-order cocrystals in general.

In this work, we synthesized three novel 4-iodotetrafluorophenoxy-azobenzene ethers, which contain different substituents (X = -H, -Cl, -CN) on the opposite side of the molecule in relation to the perhalogenated moiety carrying the iodine atom. To explore the halogen bond donor potential of the prepared compounds, we performed cocrystal screening with a series of nitrogen-containing acceptors: 1,4-diazabicyclo[2.2.2]-octane, 4-dimethylaminopyridine, 2,2'-bipyridine, 4,4'-bipyridine, 4,4'-azopyridine, N,N'-bis-(pyridin-4-yl)-methylenehydrazine, 1,2-bis-(pyridin-4-yl)-ethane, and 1,2-bis-(pyridin-4-yl)-ethylene. These three azobenzenes were selected in order to investigate how bent molecules carrying a perhalogenated moiety would act as halogen bond donors, as well as how different substituents on a distant part of the molecule could affect the formation of cocrystals. Out of 24 combinations, only 8 experiments yielded cocrystals suitable for single-crystal X-ray diffraction with two out of three azobenzene derivatives (X = -Cl and -CN). Structural analysis revealed that in all obtained cocrystals, the robust interaction is the I···N halogen bond between the azobenzene iodine atom and the acceptor nitrogen atom. A majority of cocrystals feature two donor molecules per one acceptor molecule and display crystal packing based on discrete trimeric halogen-bonded complexes. Only in the case of the 4,4'-bipyridine cocrystal with a 1:1 stoichiometry is the crystal structure based on discrete halogen-bonded dimers. In order to investigate changes in the halogen bond donor ability of the azobenzene derivatives, we have calculated values of the molecular electrostatic potential (MEP) for the DFT-optimized molecular geometries. Calculations showed that the electrostatic potential on the iodine atom only slightly depends on the functional group located on the opposite side of the molecule, with relatively large MEP values (+135 kJ mol-1 e-1 on average).

Quinazolinone Schiff base conjugates have recently attracted considerable attention from the scientific community due to their potential application as anti-cancer drugs and promising multidentate ligands. Unfortunately, reports dealing with the structural characterization of these compounds are incomprehensibly scarce. To explore the supramolecular features of these perspective compounds we have prepared and crystallized four quinazolinone Schiff base conjugates (1 = 3-{(E)-[(2-chlorophenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one, 2 = 3-{(E)-[(2,4-dihydroxyphenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one, 3 = 3-{(E)-[(2,3-dihydroxyphenyl)methylidene]amino}-2-methylquinazolin-4(3H)-one and 4 = 3-[(E)-benzylideneamino]-2-methylquinazolin-4(3H)-one). Single crystals were obtained by recrystallization of crude products from different solvents, and crystal structures were determined by single crystal X-ray diffraction. Considering their molecular structure, these compounds are similar, with the most pronounced difference being the dihedral angle between the two aromatic systems. In the crystal state, compounds with -OH groups on the benzene ring (2 and 3) are primarily connected by strong O-H & ctdot;N hydrogen bonds, and unsubstituted (4) and Cl-substituted (1) compounds via N-H & ctdot;O and C-H & ctdot;O hydrogen bonds. Thermal analysis results have shown that among these compounds the 2,4-OH substituted 2 (226 degrees C) has the highest melting point, followed by 2,3-OH substituted 3 (201 degrees C), unsubstituted 4 (192 degrees C), and the Cl-substituted 1 (159 degrees C). Additional Hirshfeld surface analysis and intermolecular energy calculations indicate that hydrogen bonds have the largest impact on thermal stability and that dispersive interactions are important for stability, but can be sterically hindered by bulky substituents on aromatic systems.

Halogen bonding enables the mechanochemical ball-milling isomerization of an otherwise persistent cis-coordinated metal complex into the corresponding trans-isomer. The importance of halogen bonding for enabling the cis→trans isomerization of the metal centre is evidenced by real-time in situ synchrotron powder X-ray diffraction monitoring of the ball-milling experiments that showed the transient appearance of a cis-geometry metal-organic halogen-bonded (MOXB) cocrystal, which is rapidly replaced by the corresponding trans-geometry one, with any excess, non-halogen-bonded cis-geometry complex being retained throughout the milling experiment. The importance of cocrystallization for cis→trans isomerization is supported by periodic density-functional theory calculations which show that the process becomes notably more enthalpically favourable in the presence of the halogen bond donor. The presented work indicates that the formation of MOXB cocrystals can open the door to new, metal-based responsive behaviours, different from those of parent solid-state coordination complexes.

We present the combined experimental and computational charge density study of halogen-bonded cocrystals containing highly unusual interactions involving heavy pnictogen acceptors. Multipole refinement against high-resolution X-ray diffraction data shows the presence of bond critical points along the I···P, I···As, and I···Sb interaction paths, as well as clear nucleophilic and electrophilic features on the electrostatic potential surfaces, marking direct evidence for the bonding character of these interactions. The experimental results are then used as a benchmark for theoretical predictions obtained from a wide variety of density functional theory (DFT) methods, allowing a direct comparison of DFT-derived charge density distributions with experiment. It is shown that calculations with different DFT functionals result in widely different interaction geometries, energies, and charge density characteristics. The presented work demonstrates the value of experimental charge density analysis in benchmarking the computational methods for reliable prediction of the structural properties of halogen-bonded materials.

A selection of 10 mono- and dihalopyridines have been used as salt coformers for benzenesulfonic and p-toluenesulfonic acids. In most cases, the resultant halopyridinium cations are bifunctional donors of both charge-assisted hydrogen and halogen bonds to the sulfonate anions.

We present the properties of an organic S = 1 antiferromagnetic chain system m-NO2PhBNO (abbreviated BoNO). In this biradical system, two unpaired electrons from aminoxyl groups are strongly ferromagnetically coupled (|JFM|/kB >= 500 K), which leads to the formation of an effective S = 1 state for each molecule. The chains of BoNO biradicals propagate along the crystallographic a axis. Temperature dependencies of the g factor and electron paramagnetic resonance (EPR) linewidth are consistent with a low-dimensional system with antiferromagnetic interactions. The EPR data further suggest that BoNO is a Haldane system with an almost isotropic g factor (2.0023 +/- 2 parts per thousand). The magnetization measurements in magnetic fields up to 40 T and low-field susceptibility, together with 1H nuclear magnetic resonance (NMR) spectra, reveal a dominant intrachain antiferromagnetic exchange coupling of J1D/kB = (11.3 +/- 0.1) K, and attainable critical magnetic fields of mu 0Hc1 2 T and mu 0Hc2 33 T. These measurements therefore suggest that BoNO is a rare example of a Haldane system with extremely small magnetic anisotropy. The present results are crucial for a future in-depth NMR study of the low-temperature Tomonaga-Luttinger liquid and magnetic field-induced phases, which can be performed in the entire phase space.

The behavior of 1,2-diiodotetrafluorobenzene (12tfib) as a halogen bond donor was studied by cocrystallizing it with a series of aromatic nitrogen bases covering a wide range of pK a values (2.10 ≤ pK a ≤ 9.60) and comparing the results with those reported for other perfluorinated iodobenzenes. The cocrystal screening was performed by grinding 12tfib and each of the selected bases in a 1:2 donor:acceptor stoichiometric ratio as well as crystallization from solution in a small excess of the acceptor (ratio 1:2.5). Of the 14 bases used in this study, three weakest bases (pK a below ca. 4) have failed to produce cocrystals, nine intermediate bases (4.85 ≤ pK a ≤ 6.72) have yielded four new phases, which were only obtainable in grinding experiments and not as pure samples, four 1:1 cocrystals and one 1:2 cocrystal, while the two strongest bases (pK a above ca. 7.5) have yielded 1:2 cocrystals. A total of eight new solids were studied by single-crystal X-ray diffraction. The three 1:2 cocrystals comprise discrete halogen-bonded trimers with 12tfib acting as a ditopic halogen bond donor to two base molecules. Among the five 1:1 cocrystals, in two, 12tfib was found to act as a monotopic donor; however, in other three, 12tfib was found to be ditopic, with the nitrogen atom of the base being a bifurcated acceptor of a pair of halogen bonds. This highly unusual binding motif has been further investigated by quantum chemical calculations and a detailed CSD survey. The computational study has found that a binding site comprising two converging iodine atoms possesses a wide, single minimum potential, which allows for a more favorable binding of weakly and intermediately basic pyridine (aromatic sp2) nitrogen atoms than a single iodine atom. The CSD survey has shown that the aromatic sp2 nitrogen atom acting as a bifurcated halogen acceptor is indeed an extremely rare occurrence (appearing in only ca. 2.2% of the total) but considerably more likely to occur in the presence of ortho-diiodo halogen bond donors.

In order to explore a strategy for synthesizing halogen-bonded metal-organic cocrystals by utilizing metal complexes whose pendant chloride group and the morpholinyl oxygen atom enables halogen bonding, we have synthesized four pentacoordinated Cu(II) and Zn(II) complexes of the MCl2L general formula (L=imines prepared by the condensation reaction of 4-aminoethylmorpholine with 2-pyridinecarboxyaldehide or 2-acetylpyridine). The prepared metal complexes were further cocrystallized with selected iodoperfluorinated benzenes. Out of 20 combinations, 14 experiments yielded crystals suitable for single-crystal X-ray diffraction. Structural analysis revealed that in 7 cocrystals halogen bonds are formed both with morpholinyl oxygen as well as with chloride atoms. In 6 cocrystals only I⋅⋅⋅Cl halogen bonds are present, while only one cocrystal exclusively featured I⋅⋅⋅Omorpholinyl halogen bonds. We observed 5 halogen bonding motifs to the MCl2 moiety, in which each chloride atom can be an acceptor of one halogen bond, two, or none at all. The most common motif in our work (6 cocrystals) is where one chlorine atom is an acceptor of one halogen bond, while the other chlorine atom does not participate in halogen bonding. The crystal packing in the prepared cocrystals is directed by halogen-bonded architectures which are either zero-, one- or two-dimensional.

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-HN-acceptor hydrogen bond between btfa and acceptor molecules, while in the one remaining cocrystal, donor and acceptor molecules are connected via the N-HN-acceptor hydrogen bond and the BrN-acceptor halogen bond. In two cocrystals of itfa, the dominant supramolecular interaction is the IN-acceptor halogen bond between itfa and acceptor molecules, while in the remaining four cocrystals, donor and acceptor molecules are additionally connected by the N-HN-acceptor 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.

Novel halogen-bonded cocrystals of seven oxazoles as multifunctional acceptors have been synthesized with selected iodoperfluorinated benzenes and structurally characterized.

This paper aims to evaluate the product contamination by elemental impurities during the mechanochemical synthesis of praziquantel (PZQ) co-crystal, polymeric dispersion and cyclodextrin complex by grinding. To assess that, PZQ was co-ground with malic acid (MA), Poloxamer F-127 (F-127) and hydroxypropyl-beta-cyclodextrin (HP beta CD) in high-energy vibrational mills using stainless steel and agate grinding tools, applying different processing time (30 and 90 min). Differential scanning calorimetry and X-ray powder diffraction confirmed the formation of the targeted products, regardless of applied processing time and grinding tool type. After digestion of the solid powder products, the levels of selected elemental impurities were analysed by inductively coupled plasma mass spectrometry (ICP-MS). The analysis revealed that the content of Mg, Ca, and V are below the limit of quantification in all samples analysed. The contents of P and Na are not related to the type of ball mill and reaction time, but to the starting materials themselves, considering that Na is found in HP beta CD and MA, while P was found in F-127. The detected Si impurities in the co-ground products can be related to the use of the agate balls and jars, while the presence of Cr and Fe can be related to the use of the stainless steel grinding tools. The risk assessment showed that the oral administration of the prepared co-ground products in quantities corresponding to regular PZQ oral doses resulted in only insignificant exposure to Cr. Finally, the use of agate grinding tools should be preferred, as administration of such products results in lower Cr exposure. The presented elemental impurities did not lead to any significant drug degradation as PZQ content at the end of the six-month testing period was still in the range of 95-105 % of the initial content. Regardless, ICP-MS analysis of the elemental impurities should be considered in regular quality control procedures in the development and production of novel pharmaceutical products prepared by grinding.

We explore the halogen bond acceptor potential of the isothiocyanate sulfur atom in the synthesis of cocrystals involving metal-organic building blocks by using Werner Ni(II) coordination compounds whose pendant isothiocyanate group enables halogen bonding. A series of 14 cocrystals involving octahedral Ni(L)(4)(NCS)(2) coordination compounds (L = pyridine or 4-methylpyridine) has been prepared by both crystallization from solution and liquid-assisted grinding. The effectiveness of this strategy is demonstrated by the assembly of a large family of cocrystals involving five perfluorinated iodobenzenes. For both coordination compounds, we generally obtained one cocrystal with each donor; in one case, we obtained an additional two stoichiomorphs, and in another, we obtained three additional solvates. Single-crystal X-ray diffraction experiments revealed that building units in all cocrystals are connected via SI halogen bonds involving the donor iodine atom and the isothiocyanate sulfur atom, which is an acceptor of two and, in some cases, even three halogen bonds. Consequently, both coordination compounds act as multitopic acceptors that can form multiple halogen bonds leading to the formation of one-, two-, and three-dimensional halogen-bonded architectures. The relative shortenings of SI distances are from 7 to 15%, while the SI-C angles are in the range from 160 to 180 degrees.

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 NI 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 NO2NO2 pnictogen bonding interactions. Computational analysis has shown that the NO2NO2 exhibits bond critical point electron densities in the region (4.897-8.306) x 10(-3) e & Aring;(-3) and interaction energies of 23.6-27.7 kJ mol(-1), whereas the NI halogen bonds generally have higher critical point electron densities ((1.795-1.937) x 10(-2) e & Aring;(-3)), but the corresponding total interaction energies are lower (19.4-20.4 kJ mol(-1)). Statistical analysis of the appearance of NO2NO2 contacts concomitantly with halogen or hydrogen bonds seems to indicate that there is a positive correlation between the presence of NO2NO2 pnictogen bonding interactions and other directional interactions in crystal structures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Periodic density-functional theory (DFT) calculations were used to predict the thermodynamic stability and the likelihood of interconversion between a series of halogen-bonded cocrystals. The outcomes of mechanochemical transformations were in excellent agreement with the theoretical predictions, demonstrating the power of periodic DFT as a method for designing solid-state mechanochemical reactions prior to experimental work. Furthermore, the calculated DFT energies were compared with experimental dissolution calorimetry measurements, marking the first such benchmark for the accuracy of periodic DFT calculations in modelling transformations of halogen-bonded molecular crystals.