Search

The crystal structures of the ligand AAZTA (6-amino-6-methylperhydro-1,4-diazepine tetraacetic acid) and of its Gd complex Na[Gd(H 2 O)AAZTA] · 3H 2 O have been determined by single crystal X-ray diffraction. The AAZTA ligand crystallizes in a zwitterion form with two deprotonated carboxylic groups and two protonated tertiary nitrogen atoms. Two independent molecules of about a similar conformation and three water molecules as asymmetric units, are present in the crystal. In the solid state the gadolinium complex is a centrosymmetric dimer with a bicapped square antiprismatic coordination geometry around each metal ion. Two symmetric bridging carboxylate groups determine the dimer formation with Gd–O(2) and Gd–O(2)′ bond distances rather comparable of 2.526(4) and 2.548(4) A, respectively, while the Gd–O(1) (inner sphere water) bond distance is 2.443(5) A. A network of hydrogen bonds between the water of inner and outer spheres and the AAZTA carboxylic groups is present in the crystal structure.

The two diastereomeric amino acid derivatives 8 (3a S ,5 R ,6a S )-5- tert -butoxycarbonylamino-4,5,6,6a-tetrahydro-3a H -cyclopenta[ d ]isoxazole-3,5-dicarboxylic acid diethyl ester, its epimer 9 (3a S ,5 S ,6a S ), and carboxylic acid 10 obtained by hydrolysis of 9 , which are intermediates in the synthesis of novel NMDA receptor antagonists 6 and 7 (Fig. 1), have been characterized by X-ray studies at 293 K for 8 and 10 , and at 100 K for 9 . The configuration of the carbon binding the 5- tert -butoxycarbonylamino moiety (BOC) determines the different molecular complexity: the chain structure for 8 , dimeric for 9 , and chain dimers for 10 . The pharmacophoric parameters in compound 8 (from which the active 7 is derived) are comparable with those observed for NMDA receptor antagonism, while 9 and 10 do not present the structural features, which match these pharmacophoric characteristics.

The crystal structures of the salts of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid with (S)-1-phenylethylamine and its p-methyl and p-nitro substituted analogues were determined in order to correlate the differences in solubility between diastereomeric salts with their solid state structures. A common characteristic of the six structures is the presence of hydrogen bond interactions, which always involve the ammonium group NH3+ and the carboxylic oxygens of three adjacent acid molecules with the formation of molecular chains in the direction of the binary screw crystallographic axis (unique axis in the monoclinic system and, in the orthorhombic space group, coincident with the direction of the shortest cell axis). A determinant factor for the high inter diastereomer solubility difference of the two pairs of p-methyl and p-nitro substituted amine salts seems, in the case of the p-methyl derivatives, to be the different mutual disposition of the acid and amine aromatic rings at the boundaries of the molecular chains and, for the p-nitro derivatives, the prevalence, in the same region, of the nitro groups or of the acid aromatic moieties. A morphologic study at SEM revealed some correlation between the crystal habit and solubility. Theoretical calculations, based on the LSER model, account for the observed solubilities in methanol.

The salts of ( S )- and ( R )-1,4-benzodioxane-2-carboxylic acid with eight ( S )-1-arylethylamines were prepared. The determination of their melting points and of their solubilities in alcohol solvents revealed large differences between the diastereomeric benzodioxanecarboxylates of ( S )-1-( p -nitrophenyl)ethylamine and of ( S )-1-( p -methylphenyl)ethylamine. Therefore, these latter amines were selected to resolve (±)-1,4-benzodioxane-2-carboxylic acid by diastereoselective crystallization finding that both of them display a very high resolution ability for such a substrate, which contrasts with the null efficiency of unsubstituted 1-phenylethylamine. These results are consistent with DSC evidences, which indicated that the two successfully resolved diastereomeric systems are binary mixtures exhibiting a eutectic with a high content of the more soluble diastereomeric salt. The new procedures can advantageously replace the two resolutions we had previously reported, that of the same acid with dehydroabietylamine and that of glycerol acetonide, a precursor of 1,4-benzodioxane-2-carboxylic acid, with 1-phenylethylamine.

The crystallographic structure of an engineered flavodoxin mutant from Desulfovibrio vulgaris has been analysed. Site-directed mutagenesis was used to substitute serine 35 with a cysteine to provide a possible covalent linkage. The crystal structure of the semiquinone form of this mutant is similar to the corresponding oxidation state of the wild-type flavodoxin. Analysis of the structural changes reveals the interaction between N(5)H of the flavin and the carbonyl O atom of Gly61 to be critical for modulation of the electrochemical properties of the protein.

The reactions of iodoflavone with 3-methyl-3-hydroxybut-1-yne and 3-methylbut-3-en-2-yne are described and the antimicrobial and cytotoxic activities of the obtained compounds have been tested. The molecular structures of 6-(3-hydroxy-3-methylbut-1-ynyl)-flavone (1a) and 6-(3-methylbut-3-en-1-ynyl) flavone (1b) have been determined by X-ray crystallography. The planar configuration of the two compounds has been attributed to intramolecular hydrogen bond interactions. In 1a, the presence of the hydroxyl group determines a dimeric arrangement of the molecules. In both compounds in the crystal state, molecular stacking has been observed.

Four new estrone derivatives were isolated after treatment of estrone 3-methyl ether (3-methoxyestra-1,3,5(10)-trien-17-one (3) with tert-butyl hydroperoxide and cobalt acetate. Three of the four steroidal compounds − the 9α-(tert-butylperoxy)-6-one 4, the 9α-hydroxy-6-one 5, and the 9β-hydroxy-6-one 7 − originated from oxidation at the 6- and 9-positions. In contrast, oxidation of 3 to a 9β-(tert-butylperoxy) compound afforded the 8-hydroxy-9-cyclodecanone derivative 6 through a molecular rearrangement involving the cleavage of the 8−9 bond. The structures of the compounds were secured by spectroscopic evidence including COSY, HSQC, and NOESY experiments combined with X-ray crystallographic analysis and molecular modeling studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The mutant S64C of the short-chain flavodoxin from Desulfovibrio vulgaris has been designed to introduce an accessible and reactive group on the protein surface. Crystals have been obtained of both the monomeric and homodimeric forms of the protein, with the cofactor FMN in either the oxidized or the one electron-reduced (semiquinone) state, and the structures have been determined to high resolution. The redox properties of the different species have been investigated and the variations observed with respect to wild type have been related to the structural changes induced by the mutation and S–S bridge formation.

Gestodene acidic treatment afforded a single rearrangement product, namely 13-beta-ethyl-18,19-dinorpregna-4,14,16-trien-3,20-dione 3, which was originated through HCl-catalyzed Rupe rearrangement. Drospirenone acidic treatment yielded two epimeric lactones by addition of HCl to the 6beta,7beta-cyclopropane ring, namely 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17beta-pregn-4-ene-21,17-carbolactone 4 and 7beta-(chloromethyl)-15beta,16beta-methylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone 5. The structure of the compounds was assessed by spectroscopic and crystallographic methods.

Two gadonilium DOTAM complexes [Gd(DOTAM)H2O](CF3SO3)3 · 3H2O (1) and [Gd(DOTAM)H2O](CF3SO3)3 · 0.5H2O · CH3CN (2) have the structure of the M isomer, with coordination geometry around the Gd ion capped square antiprismatic (SA). They differ for the Gd–Owater bond lengths of 2.396(6) and 2.474(7) A in (2) where two independent molecules are present in the crystal cell. The factors influencing the Gd–Owater bond distance, important for the water exchange rate in MRI experiments, have been correlated to the different network of hydrogen bonds involving the Gd coordinated water molecule. The X-ray structure of the parent compound [Pr(DOTAM)H2O](CF3SO3)3 · H2O · CH3CN (3) reveals an unexpected twisted square antiprismatic (TSA) coordination geometry characteristic of the m isomer.

The X-Ray crystal and molecular structures of the 4-pyrazol derivatives 3-methyl-4-diazo-5-benzamido-1H-pyrazole (4) and 3-benzamido-5-methyl-1H-pyrazole (3) have been determined. A dimeric structure has been found for the first and polymeric for the second. A comparison of 4 with 1,3-dimethyl-4-diazo-5-benzamido-lH-pyrazole (2) shows differences in the geometrical parameters of the pyrazole ring due to electron delocalization in 2 consequent to the nitrogen negative charge in the latter. Theoretical investigation at the density functional theory (DFT) level shows difference in the molecular electronic distribution of 2 and 4, in agreement with the structural parameters and the IR stretching frequencies of the respective carbonyl moieties.

Structural studies and an investigation of the cytotoxic activity of Sn(IV) complexes with N(4)-phenyl-2-benzoylpyridine thiosemicarbazone (H2Bz4Ph) were carried out. The crystal and molecular structures of [Sn(2Bz4Ph)Cl3].CH3CH2OH (1) and [Sn(2Bz4Ph)BuCl2].H2O (Bu = butyl group) (2) were determined. Both compounds present octahedral coordination geometry with the 2Bz4Ph anionic ligand behaving as tridentate on the metal ion. A comparative study of the structures of these compounds along with that of [Sn(2Bz4Ph)Bu2Cl] (3) determined before is presented. The cytotoxicity of H2Bz4Ph and its Sn(IV) complexes was investigated against the MCF-7, TK-10 and UACC-62 human tumor cell lines. Among the three complexes, 3 proved to be better as cytotoxic agent than the clinically used drug etoposide. H2Bz4Ph and all complexes were able to induce apoptosis in UACC-62 cells.