Barbara J. Oleksyn

Metal-phenoxyalkanoic acid interactions. Part 6. Crystal and molecular structure of tetraaquabis(2,4-dichlorophenoxyacetato) zinc(II)diaquabis(2,4-dichlorophenoxyacetato)zinc(II)

Abstract The crystal structure of tetraquabis(2,4-dichlorophenoxyacetato)zinc(II) diaquabis(2,4-dichlorophenoxyacetato)zinc(II) has been determined by direct methods from three-dimensional X-ray diffraction data and refined by least squares to a residual value of 0.068 for 2703 ‘observed’ reflections. Crystals are orthorhombic, space group Pna21 with 4 molecular ‘dimers’ in a cell of dimensions a = 19.302(2), b = 6.051, c = 36.325(6) A. The molecular units, {[Zn(H2O)4(2,4-D)2][Zn(H2O)2(2,4-D)2]} consist of two discrete and stereochemically different complexes, one octahedral, the other tetrahedral about the zinc centres. The six-coordination about the first Zn comprises four oxygens from aqua ligands [ZnO, 2.069(10)–2.147(9) rA] and two from the carboxyl groups of trans-related unidentate 2,4-dichlorophenoxyacetato ligands [ZnO, 2.071(9), 2.121(9) A]. The un-complexed carboxylate oxygens are tied into the complex unit by intramolecular hydrogen bonds to the water ligands (O⋯O, 2.66, 2.64 A). The four-coordination about the second Zn comprises two aqua ligands [ZnO, 2.003(10), 2.001(9) A] and two unidentate carboxyl oxygens from 2,4-dichlorophenoxyacetato ligands [ZnO, 1.915(10), 1.956(9) A]. The two units are not formally bonded but have inter-molecular O⋯O associations ranging from 2.68 to 2.85 A.

The color purple: from royalty to laboratory, with apologies to Malachowski

Abstract The components of the blood stain, eosin and methylene blue, were introduced by Baeyer and Caro, respectively. Methylene blue was used primarily for detecting Mycobacterium tuberculosis until Ehrlich in 1880 mixed methylene blue with acid fuchsin to produce what he termed a “neutral stain,” which allowed differentiation of blood cells. Eight years later, Chęciń ski changed the acidic component of the dye to eosin. Plehn subsequently altered the proportions of eosin and methylene blue to produce a greater range of red and blue hues. In 1891, Malachowski and Romanowsky independently developed stains composed of eosin and “ripened” methylene blue that not only differentiated blood cells, but also demonstrated the nuclei of malarial parasites. A number of “ripening” or “polychroming” techniques were investigated by different groups, but the aqueous dye solutions produced were unstable and precipitated rapidly. Subsequently, methanol was introduced as a solvent for the dye precipitate and techniques were developed that utilized the fixative properties of the methanolic solution prior to aqueous dilution for staining. This avoided the troublesome process of heat fixation of blood films. Giemsa further improved these techniques by using more controlled methods of methylene blue demethylation. In addition, he used measured amounts of known dyes and increased dye stability by adding glycerol to the methanol solvent. With the outbreak of World War I, it became difficult to obtain German dyes outside of Germany; during the World War II, it became impossible. In their effort to improve the inferior American versions of Giemsas stain, Lillie, Roe, and Wilcox discovered that the best staining results were obtained using pure methylene blue, one of its breakdown products (azure B) and eosin. These three substituents remain the major components of the stain to this day.

THE CRYSTAL STRUCTURE OF 2-[(N,N-DIMETHYLAMINO)METHYL]BENZENETELLURENYL CHLORIDE

The crystal structure of 2-[N,N-dimethylamino)methyl]benzenetel-lurenyl chloride (2), a compound previously formulated as bis[[2-(N,N-dimethylamino)methyl]phenyl] ditelluride bis hydrochloride (1a), was determined. In the molecule 2, tellurium is bonded to the carbon of the phenyl group [2.120(3) Å], the nitrogen of the ortho dimethylamino substituent [2.362(3) Å], and the chlorine atom [2.536(1) Å]. There also is an intermolecular interaction of the tellurium atom with the phenyl ring of a neighbouring molecule [3.655(1) Å], resulting in the formation of zigzag chains along the b axis. The noncentrosymmetric space group of the crystal can be explained by the chiral surrounding of tellurium.

X-ray and molecular modelling in fragment-based design of three small quinoline scaffolds for HIV integrase inhibitors

Crystal structures of three small molecular scaffolds based on quinoline, 2-methylquinoline-5,8-dione, 5-hydroxy-quinaldine-6-carboxylic acid and 8-hydroxy-quinaldine-7-carboxylic acid, were characterised. 5-Hydroxy-quinaldine-6-carboxylic acid was co-crystallized with cobalt(II) chloride to form a model of divalent metal cation-ligand interactions for potential HIV integrase inhibitors. Molecular docking into active site of HIV IN was also performed on 1WKN PDB file. Selected ligand-protein interactions have been found specific for active compounds. Studied structures can be used as scaffolds in fragment-based design of new potent drugs.

ALPHA -(PHENYLSELENENYL) KETONES-STRUCTURE, MOLECULAR MODELLING AND RATIONALIZATION OF THEIR GLUTATHIONE PEROXIDASE-LIKE ACTIVITY

The crystal structures of four glutathione peroxidase mimetics- 1-(4-nitrophenyl)-2-(phenylselenenyl)ethanone (1), 2-(phenylselenenyl)-1-(2-thienyl)ethanone (3), 1-(2-naphthyl)-2-(phenylselenenyl)e ...

Cobalt complex of cinchonine: intermolecular interactions in two crystalline modifications.

Two crystalline modifications of cinchonine cobalt complex, C19H23Cl3CoN2O, were obtained from mixture of saturated alcohol solutions of CoCl3 x 6H2O and cinchonine. The X-ray structure analysis revealed that the asymmetric unit of one modification, CoCn1, contains only zwitterionic molecules of the complex. In the asymmetric unit of the other, CoCn2, there are two molecules of the title compound and two molecules of ethanol. The influence of the absolute configuration, the CoCl3 coordination with quinoline, and the presence of alcohol molecules on the studied structures was established by comparison of the crystal and molecular structures of both cobalt complexes with the analogous quinine complex and zinc complex of cinchonine. The interactions that dominate in the packing of the molecules in both structures are intermolecular hydrogen bonds. They form characteristic ring systems, depending on the presence of the alcohol molecules. The ring features are also related to the absolute configuration of the alkaloid.

In search of the malarial parasite

Methylene blue was synthesized by Caro in 1876 at BASF, a chemical company. Six years later, Koch employed methylene blue when he discovered the tubercle bacillus. In 1880, Ehrlich described what he termed “neutral” dyes: mixtures of acidic and basic dyes for the differentiation of cells in peripheral blood smears. Bernthsen prepared in 1886 a relatively pure dye, obtained by decomposition of methylene blue, and called it methylene azure. In 1891, Malachowski developed a method which used mixtures of eosin and “ripened” methylene blue that not only differentiated blood cells, but also demonstrated the nuclei of malarial parasites. Romanowsky later performed the same feat with an unrepeatable method. A number of “ripening” (polychroming) techniques were investigated by different groups (Nocht 1899) but the aqueous dye solutions produced were unstable and precipitated rapidly. Subsequently, methanol was introduced as a solvent for the dye precipitate (Jenner 1899) and techniques were developed that utilized the fixative properties of the methanolic solution prior to aqueous dilution for staining (Wright 1902). Giemsa (1902) further improved these techniques by developing more precise methods of methylene blue demethylation and adding glycerol as a stabilizing agent to the methanol solvent. Today, the Malachowski−Wright−Giemsa stain continues to be regarded as the world’s standard diagnostic technique for malaria.

New crystalline complex of quinine and quinidine.

A new complex of diastereoisomeric pair, quinine and quinidine (QQd), was obtained from a mixture of saturated ethanol solutions of quinine and quinidine (0.5:1). The complex crystallises in the triclinic system, space group P1, and contains two molecules of quinine, two molecules of quinidine and four water molecules in the asymmetric unit. The X-ray structure analysis of a single crystal revealed that quinine and quinidine molecules occur in the so-called open conformation, characteristic for Cinchona alkaloids, whenever they are engaged in intermolecular hydrogen bonds. Quinine and quinidine molecules are organized in two very similar kinds of chains. In each chain the links that contain 14-membered rings can be distinguished. Within these rings quinine and quinidine molecules interact via intermolecular hydrogen bonds between the quinuclidine nitrogens and hydroxyl groups, mediated by water molecules. The links are connected with each other by hydrogen bonds between water molecules and nitrogens of the quinoline moieties, which interact via pi-pi stacking. The architecture of the hydrogen bond system in QQd, compared to those observed in the crystal structures of nonhydrated quinidine, cinchonine and cinchonidine, reveals the effect of the co-crystallizing water on the molecular packing. In nonhydrated alkaloid structures the hydrogen-bonded molecules form helical chains, different from those observed in the hydrated QQd complex and hydrated quinine toluene solvate (QTol). Comparison of QQd structure with that of QTol suggests that while the intermolecular hydrogen bonds in the system quinine-water-quinidine-water are very similar to those in quinine-water-quinine-water system, the mode of pi-pi interaction between their quinoline moieties depends on the absolute configuration of the interacting alkaloid molecules.

The Crystal and Molecular Structure of 3-Methyl-5-p-methylbenzylidene-2-selenohydantoin

The X-ray structure analysis of a single crystal of 3-methyl-5-p-methylbenzylidene-2-selenohydantoin was carried out. The crystals are monoclinic, space group P2 1 /c, with a = 5.244(1) Å, b = 19.402(2) Å, c = 11.606(1) Å, g = 94.64(1)°;, Z = 4. The molecule is a Z-isomer. The overall conformation is not exactly planar, the angle between the hydantoin and p-methylphenyl planes is 11.8(1)°;. The packing of the molecules in the unit cell can be described as an arrangement of molecular chains which interact with each other via weak-hydrogen bonds, C--H·;·;·;O. The chains consist of dimers in which molecules are linked together by two symmetry-equivalent hydrogen bonds, N--H·;·;·;Se, that form accros inversion centres. The dimers interact also via weak hydrogen bonds, C--H·;·;·;O, between methyl groups and carbonyls of molecules related by another inversion centres.

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC50 for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC50 of 47 nm) showed improved antiplasmodial activity in comparison with EA alone.