The synthesis and characterization of a series of cocrystals of an isoniazid derivative with butan-2-one and propan-2-one.

Four cocrystals containing N'-(butan-2-ylidene)pyridine-4-carbohydrazide (izbt) and one cocrystal containing N'-isopropylideneisonicotinohydrazide (izact) were synthesized by reacting isoniazid with either butan-2-one (for the former) or acetone (for the latter). The coformers used to synthesize the izbt cocrystals were 2,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, 2-chloro-4-nitrobenzoic acid and 1-naphthoic acid. 1-Naphthoic acid was also used with izact to form a cocrystal. The 1:1 cocrystals are: N'-(butan-2-ylidene)pyridine-4-carbohydrazide-1-naphthoic acid (izbt-1nta), C10H13N3O·C11H8O2, N'-(butan-2-ylidene)pyridine-4-carbohydrazide-2,4-dihydroxybenzoic acid (izbt-2,4-dhba), C10H13N3O·C7H6O4, N'-(propan-2-ylidene)pyridine-4-carbohydrazide-1-naphthoic acid (izact-1nta), C9H11N3O·C11H8O2, N'-(butan-2-ylidene)pyridine-4-carbohydrazide-2-chloro-4-nitrobenzoic acid (izbt-2c4n), C10H13N3O·C7H4ClNO4, and N'-(butan-2-ylidene)pyridine-4-carbohydrazide-2,5-dihydroxybenzoic acid (izbt-2,5-dhba), C10H13N3O·C7H6O4. The cocrystals containing izbt were compared to those containing the same (or similar) coformers with izact that have been reported either here or in the Cambridge Structural Database (CSD). Most of the cocrystals showed different packing despite having the same hydrogen-bonding motifs. The cocrystals were characterized by single-crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC).

Co-crystallization of N'-benzyl-idene-pyridine-4-carbohydrazide and benzoic acid via autoxidation of benzaldehyde.

The 1:1 co-crystal N'-[(2-methyl-phen-yl)methyl-idene]pyridine-4-carbohydrazide-benzoic acid (1/1), C13H11N3O·C7H6O2, formed unexpectedly after autoxidation of benzaldehyde during the slow evaporation process of a solution of isoniazid in benzaldehyde. The original intent of the synthesis was to modify isoniazid with benzaldehyde and crystallize the product in order to improve efficacy against Mycobacteria species, but benzoic acid formed spontaneously and co-crystallized with the intended product, N'-benzyl-idene-pyridine-4-carbohydrazide.

Observation of High Magnetic Bistability in Lanthanide (Ln = Gd, Tb and Dy)-Grafted Carbon Nanotube Hybrid Molecular System.

There is an immense research interest in molecular hybrid materials posing novel magnetic properties for usage in spintronic devices and quantum technological applications. Although grafting magnetic molecules onto carbon nanotubes (CNTs) is nontrivial, there is a need to explore their single molecule magnetic (SMM) properties post-grafting to a greater degree. Here, we report a one-step chemical approach for lanthanide-EDTA (Ln = GdIII, 1; TbIII, 2 and DyIII, 3) chelate synthesis and their effective grafting onto MWCNT surfaces with high magnetic bistability retention. The magnetic anisotropy of an Ln-CNT hybrid molecular system by replacing the central ions in the hybrid complex was studied and it was found that system 1 exhibited a magnetization reversal from positive to negative values at 70 K with quasi-anti-ferromagnetic ordering, 2 showed diamagnetism to quasi-ferromagnetism and 3 displayed anti-ferromagnetic ordering as the temperature was lowered at an applied field of 200 Oe. A further analysis of magnetization (M) vs. field (H) revealed 1 displaying superparamagnetic behavior, and 2 and 3 displaying smooth hysteresis loops with zero-field slow magnetic relaxation. The present work highlights the importance of the selection of lanthanide ions in designing SMM-CNT hybrid molecular systems with multi-functionalities for building spin valves, molecular transistors, switches, etc.

Chains or rings? Polymorphism of an isoniazid derivative derivatized with diacetone alcohol.

Isoniazid was derivated with diacetone alcohol in a Schiff-base reaction in order to yield N'-[(2E)-4-hydroxy-4-methylpentan-2-ylidene]pyridine-4-carbohydrazide. The resulting product was determined to be polymorphic, exhibiting two crystal forms: form I and form II. From the crystal structure determination using SC-XRD it was determined that form I crystalizes in the C2/c space group while form II crystalizes in the P21/c space group. The hydrogen bonding patterns of both forms are distinctively different from each other: form I forms a chain hydrogen bond motif by forming a hydrogen bond between the hydroxyl group and the oxygen of the amide group while form II forms dimers with a ring hydrogen bond motif forming between the hydroxyl group and the pyridine group. From DSC analysis form I and form II are enantiotropically related, with form I converting to form II at 132.3 °C before melting at 142.3 °C. Based on both experimental and computational evidence, we conclude that form I is a metastable form, with form II being the most stable form. This is another case of a "disappearing polymorph."

Thermochromic Phase Transitions of Long Odd-Chained Inorganic-Organic Layered Perovskite-Type Hybrids [(CnH2n+1NH3)2PbI4], n = 11, 13, and 15.

We investigate the last members of a series of inorganic-organic hybrid materials of the general formula [(CnH2n+1NH3)2PbI4] (abbreviated CnPbI). The self-assembly of the inorganic and organic components has a perovskite-like structure as the two-dimensional (2D) inorganic layers have four corners of the lead(II) iodide octahedra being shared out. The inorganic layers are separated by bilayers of alkylammonium chains, in this case with n = 11, 13, and 15. These materials exhibit complex phase behavior in the temperature range from -20 to + 81 °C. Differential scanning calorimetry and single-crystal X-ray diffraction enabled the phase transition temperatures and enthalpies to be determined and the structural changes that occur at the phase transition temperature. The number of phases is dependent on the chain length: for n = 11 and 15, there are three phases, and for n = 13, there are four phases. Regardless of the number of phases, all three compounds have identical lowest-temperature phases (all stable below room temperature), which have inorganic layers that are staggered, alkylammonium chains that are planar and nonplanar, and yellow crystals. The room-temperature phases for the three compounds differ, but all are orange. C11PbI has staggered layers, and C13PbI and C15PbI have identical room-temperature phases with eclipsed layers. C13PbI and C15PbI also show an additional phase between the lowest-temperature and room-temperature phases.

2-Chloro-4-nitrobenzoic acid as a coformer with pharmaceutical cocrystals and molecular salts.

A series of five binary complexes, i.e. three cocrystals and two molecular salts, using 2-chloro-4-nitrobenzoic acid as a coformer have been produced with five commonly available compounds, some of pharmaceutical relevance, namely, 2-chloro-4-nitrobenzoic acid-isonicotinamide (1/1), C7H4ClNO4·C6H6N2O, 2-chloro-4-nitrobenzoic acid-3,3-diethylpyridine-2,4(1H,3H)-dione (2/1), 2C7H4ClNO4·C9H13NO2, 2-chloro-4-nitrobenzoic acid-pyrrolidin-2-one (1/1), C7H4ClNO4·C4H7NO, 2-carboxypiperidinium 2-chloro-4-nitrobenzoate, C6H12NO2-·C7H3ClNO4-, and (2-hydroxyethyl)ammonium 2-chloro-4-nitrobenzoate, C2H8NO+·C7H3ClNO4-. The coformer falls under the classification of a `generally regarded as safe' compound. All five complexes make use of a number of different heteromeric hydrogen-bonded interactions. Intermolecular potentials were evaluated using the CSD-Materials module.

Fischer Carbene Complexes of Iridium(I) for Application in Catalytic Transfer Hydrogenation.

New examples of the very rare class of iridium(I) Fischer carbene complexes (FCCs) are reported from the facile transmetalation from group 6 FCCs. Postcomplexation modification of either the carbene ligand or the ancillary coligands results in a tunable IrI metal center, for unprecedented application as a (pre)catalyst in a benchmark transfer hydrogenation reaction. The introduction of an aminocarbene ligand with a pendant N-donor moiety capable of hemilabile coordination yielded the best catalytic results with turnover frequencies reaching 445 h-1 and requiring 0.1 mol % catalyst and 0.5 mol % base loading, respectively.

Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-tert-butylbenzoic acid with isoniazid and its derivatized forms.

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4-tert-butylbenzoic acid via a one-pot covalent and supramolecular synthesis, namely 4-tert-butylbenzoic acid-isoniazid, C6H7N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(propan-2-ylidene)isonicotinohydrazide, C9H11N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(butan-2-ylidene)isonicotinohydrazide, C10H13N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(diphenylmethylidene)isonicotinohydrazide, C19H15N3O·C11H14O2, and 4-tert-butylbenzoic acid-N'-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C12H17N3O2·C11H14O2. The co-former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan-2-one, butan-2-one, benzophenone and 3-hydroxy-3-methylbutan-2-one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.

A new polymorph of ammonium succinate - serendipity in action.

Succinic acid has been known since 1546 and was first chemically identified in the mid-19th century. In an attempt to prepare a molecular salt of succinic acid with (S)-(-)-α-methylbenzylamine, we have obtained the second polymorph of the monoammonium salt of succinic acid, NH4+·C4H5O4-. The crystal structure determination proves the structure of the ionic compound and the intimate role of the ammonium ion in the structure, which is compared to the earlier described polymorph.

Binary charge-transfer complexes using pyromellitic acid dianhydride featuring C-H⋯O hydrogen bonds.

Four binary charge-transfer complexes were made using pyromellitic acid dianhydride (pmda), those being pmda-naphthalene (1/1), C10H2O6·C10H8, (I), pmda-fluoranthene (1/1), C10H2O6·C16H10, (II), pmda-9-methyl-anthracene (1/1), C10H2O6·C15H12, (III), and pmda-ethyl anthracene-9-carboxyl-ate (1/2), C10H2O6·2C17H12O3, (IV). All charge-transfer complexes show alternating donor and acceptor stacks, which have weak C-H⋯O hydrogen bonds connecting the donor and acceptor mol-ecules. In addition, complex (I) has Z' = 1/2, complex (II) has a Z' = 2 and complex (IV) has half mol-ecule of pyromellitic acid dianhydride in the asymmetric unit.

Binary polymorphic cocrystals: an update on the available literature in the Cambridge Structural Database, including a new polymorph of the pharmaceutical 1:1 cocrystal theophylline-3,4-dihydroxybenzoic acid.

An analysis and classification of the 2925 neutral binary organic cocrystals in the Cambridge Structural Database is reported, focusing specifically on those both showing polymorphism and containing an active pharmaceutical ingredient (API). The search was confined to molecules having only C, H, N, O, S and halogens atoms. It was found that 400 out of 2925 cocrystals can be classified as pharmaceutical cocrystals, containing at least one API, and that of those, 56 can be classified as being polymorphic cocrystals. In general, the total number of polymorphic cocrystal systems of any type stands at 125. In addition, a new polymorph of the pharmaceutical cocrystal theophylline-3,4-dihydroxybenzoic acid (1/1), C7H8N4O2·C7H6O4, is reported.

Binary and ternary charge-transfer complexes using 1,3,5-tri-nitro-benzene.

Three binary and one ternary charge-transfer complexes have been made using 1,3,5-tri-nitro-benzene, viz. 1,3,5-tri-nitro-benzene-2-acetylnaphthalene (1/1), C6H3N3O6·C12H10O, (I), 1,3,5-tri-nitro-benzene-9-bromo-anthracene (1/1), C14H9Br·C6H3N3O6, (II), 1,3,5-tri-nitro-benzene-methyl red (1/1), C15H15N3O2·C6H3N3O6, (III) (systematic name for methyl red: 2-{(E)-[4-(di-methyl-amino)-phen-yl]diazen-yl}benzoic acid), and 1,3,5-tri-nitro-benzene-1-naphthoic acid-2-amino-5-nitro-pyridine (1/1/1), C6H3N3O6·C11H8O2·C5H5N3O2, (IV). All charge-transfer complexes show alternating donor and acceptor stacks, which have weak C-H⋯O hydrogen bonds perpendicular to the stacking axis. In addition, complex (IV) is a crystal engineering attempt to modify the packing of the stacks by inserting a third mol-ecule into the structure. This third mol-ecule is stabilized by strong hydrogen bonds between the carb-oxy-lic acid group of the donor mol-ecule and the pyridine acceptor mol-ecule.

An investigation to elucidate the factors dictating the crystal structure of seven ammonium carboxyl-ate mol-ecular salts.

The crystal structures of seven ammonium carboxyl-ate salts are reported, namely (RS)-1-phenyl-ethan-1-aminium isonicotinate, C8H12N+·C6H4N1O2-, (I), (RS)-1-phenyl-ethan-1-aminium flurbiprofenate [or 2-(3-fluoro-4-phenyl-phen-yl)propano-ate], C8H12N+·C15H12FO2-, (II), (RS)-1-phenyl-ethan-1-aminium 2-chloro-4-nitro-benzoate, C8H12N+·C7H3ClNO4-, (III), (RS)-1-phenyl-ethan-1-aminium 4-iodo-benzoate, C8H12N+·C7H4IO2-, (IV), (S)-1-cyclo-hexyl-ethan-1-aminium 2-chloro-4-nitro-benzoate, C8H18N+·C7H3ClNO4-, (V), 2-(cyclo-hex-1-en-1-yl)ethan-1-aminium 4-bromo-benzoate, C8H16N+·C7H4BrO2-, (VI), and (S)-1-cyclo-hexyl-ethan-1-aminium 4-bromo-benzoate, C8H18N+·C7H4BrO2-, (VII). Salts (II) to (VII) feature three N+-H⋯O- hydrogen bonds, which form one-dimensional hydrogen-bonded ladders. Salts (II), (III), (IV), (V) and (VII) have a type II ladder system despite the presence of halogen bonding and other inter-molecular inter-actions, whereas (VI) has a type III ladder system. Salt (I) has a unique hydrogen-bonded system of ladders, featuring both N+-H⋯O- and N+-H⋯N hydrogen bonds owing to the presence of the pyridine functional group. The presence of an additional hydrogen-bond acceptor on the carboxyl-ate cation disrupts the formation of the ubiquitous type II and III ladder found predominately in ammonium carboxyl-ate salts. Halogen bonding, however, has no influence on their formation.

Crystal structure of 5-[2-(2,4,6-tri-bromo-phen-yl)diazen-yl]tropolone.

The title compound {systematic name: 2-hy-droxy-5-[2-(2,4,6-tri-bromo-phen-yl)diazen-1-yl]cyclo-hepta-2,4,6-trien-1-one}, C13H7Br3N2O2, is essentially planar, with an r.m.s. deviation of 0.054 Å. The mol-ecular structure is fixed in the azo tautomer by intra-molecular C-H⋯N inter-actions, with O-H⋯O hydrogen bonds creating linked dimers. Charge-transfer inter-actions are observed, with the segregated stacks linked by Br⋯Br inter-actions.

Crystal structure of bromido(η6-1-isopropyl-4-methylbenzene)(7-oxocyclohepta-1,3,5-trien-1-olato-κ2O,O')osmium.

In the title compound, [OsBr(C10H14)(C7H5O2)], the central OsII ion is ligated by a hexa-haptic η6p-cymene ring, a Br- ligand and two O atoms of a chelating tropolonate group. The p-cymene ligand presents more than one conformation, giving rise to a discrete disorder, which was modelled with two different orientations with occupancy values of 0.561 (15) and 0.439 (15). The crystal packing features C-H⋯O and C-H⋯Br hydrogen bonding. Aromatic π-π stacking inter-actions are also observed between adjacent non-benzenoid aromatic tropolone rings.

Prevalent polymorphism in benzophenones.

We report here the crystal structures of dimorphs of 4-hydroxybenzophenone, C13H10O2, and 4-(dimethylamino)benzophenone, C15H15NO, as well as trimorphs of 4,4'-dimethylbenzophenone, C15H14O. The polymorphs were isolated from slow-evaporation conditions or from cocrystallization attempts. The main differences between the polymorphs involve differences in packing rather than differences in conformation, owing to the limited conformational freedom of the three molecules. 4-Hydroxybenzophenone is the exception, exhibiting almost identical packing arrangements in the two polymorphs, with the only major changes being in the interplanar orientations. The lattice energies of the respective polymorphs of the three compounds reported here are all within 1 kcal mol-1 of each other. The existence of nine further polymorphic benzophenone derivatives in the literature suggests that there is a good deal of polymorphic space in this class of compounds.

Stoichiometric and polymorphic salts of hexa-methyl-ene-tetra-minium and 2-chloro-4-nitro-benzoate.

Four mol-ecular salts made from hexa-methyl-ene-tetra-minium and 2-chloro-4-nitro-benzoate have been synthesized and are reported, namely ammonium hexa-methyl-ene-tetra-minium bis-(2-chloro-4-nitro-benzoate), NH4+·C6H13N4+·2C7H3ClNO4-, (I), hexa-methyl-ene-tetra-minium hydrogen bis-(2-chloro-4-nitro-benzoate), 0.5C6H13N4+·C7H3.50ClNO4-, (II), hexa-methyl-ene-tetra-minium 2-chloro-4-nitro-benzoate, C6H13N4+·C7H3ClNO4-, (IIIa) and (IIIb). All four mol-ecular salts show N+-H⋯O- hydrogen bonding. Salt (I) crystallized out with an NH4+ counter-ion which came from decomposition of 50% of the hexa-methyl-ene-tetra-minium cation in solution. (II) shows an unusual asymmetric unit, with both a hexa-methyl-ene-tetra-minium cation and a partially deproton-ated 2-chloro-4-nitro-benzoate anion. Salts (IIIa) and (IIIb) are polymorphs of each other. This work shows that hexamethylenetetramine only protonates once, even in the presence of excess acid.

Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity.

A small library of novel copper and zinc imidazo[1,2-a]pyridine complexes have been synthesized. Their structures were confirmed by X-ray diffraction crystallography and a selection of these compounds was tested against five cancer cell lines originating from breast cancer (MCF-7 and MDA-MB-231), leukemia (K562 and HL-60) and colorectal cancer (HT-29). The imidazo[1,2-a]pyridines and their zinc complexes showed poor anticancer activity, while the copper complexes were active against the cancer cell lines with IC50 values comparable to and lower than camptothecin. For example, copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 had an IC50 value lower than 1 µM against the HT-29 cells. Fluorescence microscopy with acridine orange, Hoechst 33342 and ethidium bromide, used in a preliminary investigation to evaluate morphological changes showed that copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 caused both apoptosis, necrosis and paraptosis in the MCF-7 and HL-60 cells. A select group of copper N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amines (26, 27, 29 and 31) induced apoptosis, paraptosis and deformed nuclei in MCF-7 cells.

A structural study of 4-aminoantipyrine and six of its Schiff base derivatives.

Six derivatives of 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one (4-aminoantipyrine), C11H13N3O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen-bonding motifs compared to the original 4-aminoantipyrine. The derivatives were synthesized from the reactions of 4-aminoantipyrine with various aldehyde-, ketone- and ester-containing molecules, producing (Z)-methyl 3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]but-2-enoate, C16H19N3O3, (II), (Z)-ethyl 3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]but-2-enoate, C17H21N3O3, (III), ethyl 2-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]cyclohex-1-enecarboxylate, C20H25N3O3, (IV), (Z)-ethyl 3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-3-phenylacrylate, C22H23N3O3, (V), 2-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C14H14N4O2, (VI), and (E)-methyl 4-{[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]methyl}benzoate, C20H19N3O3, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N-H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six-membered intramolecular N-H...O hydrogen-bonded ring in (II)-(V) and an intermolecular N-H...O hydrogen bond in (VI), whereas there is an intramolecular C-H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π-π interactions, while C-H...π interactions are observed in (II), C-H...O interactions are observed in (I), (III), (V) and (VI), and a C-O...π interaction is observed in (II).