Marcus Layh

Polymorphism and phase transformations in 2,6-disubstituted N-phenylformamides: the influence of hydrogen bonding, chloro-methyl exchange, intermolecular interactions and disorder

The crystal structures, thermal behaviour and phase transformations of a series of 2,6-disubstituted-N-phenylformamides have been investigated. A phase transformation was only observed when chlorine was one of the substituents. Crystals of the room-temperature form of 2,6-dichloro-N-phenylformamide (1) and 2-chloro-6-methyl-N-phenylformamide (2) are isomorphous. Both compounds are orthorhombic at room temperature and transform to a monoclinic high-temperature form at 155 and 106 °C, respectively. The room-temperature structures of 1 and 2 consist of chains of N–H⋯O hydrogen-bonded molecules stacked in an alternating arrangement along the crystallographic a direction. The high-temperature forms of compounds 1 and 2 (grown by sublimation) are both monoclinic but not isomorphous, with one short axis of about 4.3 A, and consist of chains of N–H⋯O hydrogen-bonded molecules stacked along the short axis, related by translation. When both of the chlorine substituents are replaced by methyl groups, as in 2,6-dimethyl-N-phenylformamide (3), the crystals do not undergo any phase transition on heating and only an orthorhombic form, space group P212121, has been isolated. Examination of the molecular geometry and structural properties of 3 indicates that it is a hybrid structure of the low- and high-temperature forms of compounds 1 and 2. This contribution analyzes the effect of chloro-methyl exchange, the steering ability of chlorine, and the role of weak interactions on the structural and thermal properties of the compounds studied. In addition, a mechanism for the phase change in 1 is proposed and rationalized through the examination of the structures themselves together with lattice energy calculations.

The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations

In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)2]Cl and [B] [Au(d4pype)2]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH2)(dpmaaSnMe2)]Cl and [D] [Au(dpmaaSnMe2)2]Cl as antimitochondrial agents. The results of this study indicate that [C] and [D] have intermediate partition coefficients and exhibited a selective uptake by cells. They exhibited a higher selectivity for the various cell lines than [A] but were more cytotoxic than [B]. There is a significant correlation between the cytotoxic potential of [A], [B], [C], and [D] and their octanol/water partition coefficients in both MCF-7 (breast cancer) and MCF-12A (nonmalignant breast) cells, whereas their cytotoxic potential and ability to induce the release of cytochrome c correlated only in the case of the MCF-12A cells. Complexes [C] and [D] are promising new chemotherapeutic drugs. These compounds target the mitochondrial membranes of certain cancer cells exploiting the differences between the mitochondrial membrane potential of these cells and normal cells. Although the concentrations of these compounds necessary to eradicate cancer cells are very high, the results provide a basis for the synthesis of a new family of compounds with intermediate partition coefficients compared to [A] and [B] but with increased activity against cancer cells.

Cocrystal of cis- and trans-N-phenyl- formamide

N-Phenylformamide, C(7)H(7)NO, crystallizes with two molecules in the asymmetric unit which have different conformations of the formylamino group, one being cis and the other trans. This is the first example of an arylformamide crystal containing both conformational isomers and it may thus be considered a cocrystal of the two conformers. The two molecules in the unit cell are linked through N-H...O hydrogen bonding to two other molecules, thereby forming hydrogen-bonded tetramers within the crystal structure.

Cobalt Ion Incorporation into Periodic Mesoporous Organosilica Materials Synthesized by Co-condensation of 1,2-Bistrimethoxysilylethane with 3-Glycidoxypropyltriethoxysilane

Bifunctional periodic mesoporous organosilica materials with and without cobalt ion incorporation were synthesized by co-condensation of 1,2-bistrimethoxysilylethane (BTME) with 3-glycidoxypropyltriethoxysilane (GPTS) in the presence of cetyltrimethylammonium bromide. Nitrogen gas adsorption on samples with varying ratios of BTME:GPTS revealed that increasing the amount of GPTS affects pore size, surface area and pore volume as well as shapes of the isotherms and hysteresis loops. The hysteresis loops of the Type IV isotherms obtained for GPTS-modified ethane silica materials (without cobalt ion) change from Type H3 to Type H4 with increasing GPTS content. There is a tendency for pore sizes to change from mesopore to micropore when the amount of GPTS is increased. Isotherms of cobalt ion incorporated GPTS-modified ethane silica materials change from Type IV to Type I with increasing GPTS content. The surface area, pore volume and pore diameter decrease with increasing loading of GPTS as well as after cobalt ion incorporation. Thermogravimetric analysis and differential thermal analysis show that the surfactant is removed by solvent extraction. Cobalt ion incorporation is confirmed by powder X-ray diffraction and Raman spectroscopy.

The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics

The anti-tumour activity of the Au (I) phosphine complex [Au(dppe(2)]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)(2)]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)(2)]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the in vitro and in vivo studies. Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.

Tris(2-pyridyl)phosphine oxide: how C-H.O and C-H.N interactions can affect crystal packing efficiency.

Tris(2-pyridyl)phosphine oxide, (I), C(15)H(12)N(3)OP, is isomorphous with tris(2-pyridyl)phosphine. Because of a combination of C-H.O and C-H.N interactions, the crystal packing is denser in the title compound than in the related compounds triphenylphosphine oxide and tris(2-pyridyl)phosphine.

2, 2'-Bipyridinium (1+) bromide monohydrate

In the crystal structure of 2,2-bipyridinium(1+) bromide monohydrate, C(10)H(9)N(2)(+).Br(-).H(2)O, the cation has a cisoid conformation with an intramolecular N-H.N hydrogen bond. The cation also forms an N-H.O hydrogen bond to an adjacent water molecule, which in turn forms O-H.Br(-) hydrogen bonds to adjacent Br(-) anions. In this way, a chain is formed extending along the b axis. Additional interactions (C-H.Br(-) and pi-pi) serve to stabilize the structure further.

2,4,6-Trimethylphenyl isocyanide

The title compound, C(10)H(11)N, displays a crystallographic mirror plane that incorporates all the non-H atoms, as well as the H atoms attached to the aromatic ring. The isocyano group is almost linear and shows an N[triple bond]C bond distance of 1.158 (3) A.

Two polymorphs of N-(2,6-difluorophenyl)formamide.

The structures of two distinct polymorphic forms of N-(2,6-difluorophenyl)formamide, C(7)H(5)F(2)NO, have been studied using single crystals obtained under different crystallizing conditions. The two forms crystallize in different space groups, viz. form (Ia) in the orthorhombic Pbca and form (Ib) in the monoclinic P2(1) space group. Each polymorph crystallizes with one complete molecule in the asymmetric unit and they have a similar molecular geometry, showing a trans conformation with the formamide group being out of the plane of the aromatic ring. The packing arrangements of the two polymorphs are quite different, with form (Ia) having molecules that are stacked in an alternating arrangement, linked into chains of N-H...O hydrogen bonds along the crystallographic a direction, while form (Ib) has its N-H...O hydrogen-bonded molecules stacked in a linear fashion. A theoretical study of the two structures allows information to be gained regarding other contributing interactions, such as pi-pi and weak C-H...F, in their crystal structures.

An N-lithio-indole from the reaction of LiCH(TMS)2 and PhNC

The reaction of LiCH(TMS)2 with phenyl isocyanide PhNC has unexpectedly led to the N-lithio-indole derivative 1, that has been fully characterised including its X-ray crystal structure determination.