Isostructurality in crystalline oxa-androgens: a case of C-O-···O and C-H···O interaction mimicry and solid solution formation

A C-H···O interaction in 2-oxa-4-androstene-3,17-dione is replaced by a C-O-H···O hydrogen bond in the isostructural 6a-hydroxy analogue, and these compounds form a binary solid solution, showing the similarity of these two crystal structures

Synthesis and mechanistic studies of diketo acids and their bioisosteres as potential antibacterial agents

A series of diketo esters and their pertinent bioisosteres were designed and synthesized as potent antibacterial agents by targeting methionine amino peptidases (MetAPs). In the biochemical assay against purified MetAPs from Streptococcus pneumoniae (SpMetAP1a), Mycobacterium tuberculosis (MtMetAP1c), Enterococcus faecalis (EfMetAP1a) and human (HsMetAP1b), compounds 3a, 4a and 5a showed more than 85% inhibition of all the tested MetAPs at 100 μM concentration. Compounds 4a and 5a also exhibited antibacterial potential with MIC values 62.5 μg/mL (S. pneumoniae), 31.25 μg/mL (E. faecalis), 62.5 μg/mL (Escherichia coli) and 62.5 μg/mL (S. pneumoniae), 62.5 μg/mL (E. coli), respectively. Moreover, 5a also significantly inhibited the growth of multidrug resistant E. coli strains at 512 μg/mL conc., while showing no cytotoxic effect towards healthy CHO cells and thus being selected. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 5a. TEM analysis also displayed vital damage to bacterial cells by 5a at MIC conc. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 5a as visualized by SEM micrographs. Interestingly, 5a did not cause an alteration in the hemocyte density in Galleria mellonella larvae which is considered in vivo model for antimicrobial studies and was non-toxic up to a conc. of 2.5 mg/mL

Crystallization of pseudopolymorphs of some gamboge pigments. Pyridine, dimethylformamide and dimethylsulfoxide solvates of morellic acid, gambogic acid and guttiferic acid

Morellic acid, gambogic acid and guttiferic acid are related naturally-occurring xanthone pigments that yield X-ray quality crystals only from solvents like pyridine, dimethylformamide (dmf) and dimethyl sulfoxide (dmso). The structures of four of these crystals have been determined and are found to contain solvents of crystallization. The solvents hydrogen bond to the carboxyl groups with O-H…O/N motifs previously seen in other carboxylic acids. Distinctive, however, is the presence of an extended though somewhat diffuse array of C-H…O hydrogen bonds that aggregates the entire solute-solvent assemblage in a multi-point manner. Pyridine and dmf are able to mimic each other with respect to their hydrogen bond donating and accepting characteristics and in this respect play equivalent roles in their solvates with morellic acid and gambogic acid. Dmso is seen to self-associate in its guttiferic acid solvate. It is possible that these solvents with multiple hydrogen bonding donor and acceptor capability can act as hydrogen bond nucleators, providing just enough rigidity to the solutes to ensure crystallization

Crystal chemistry of some synthetic 2-oxa-steroids: conformation, packing motifs and isostructurality

The crystal structures of six synthetic 2-oxa-steroids (A-ring lactone steroids) have been determined by single-crystal X-ray diffraction. The conformation and hydrogen bonding in these oxa-steroids is compared with packing motifs in the natural steroids and the anabolic agent, Anavar®. O—H...O hydrogen bonding with lactone carbonyl O is the preferred arrangement in molecules with a C—OH group. The donor H atoms of A, B and D rings participate in C—H...O interactions with lactone carbonyl O and D-ring hydroxyl/ketone O acceptor atoms. The conformation of the lactone ring in these analogues is different from the natural androgens because replacement of the C2-methylene group by an O atom changes the geometry of the A ring. Two structurally related lactone steroids provide the first example of O—H...O/C—H...O interaction mimicry and furthermore the two components form a binary solid solution. The O—H...O and C—H...O hydrogen bonds in 2-oxa-steroid crystal structures are analysed and the observed preferences discussed in terms of geometric and chemical factors.</jats:p

Structural characterization of the protein cce_0567 from Cyanothece 51142, a metalloprotein associated with nitrogen fixation in the DUF683 family

The genomes of many cyanobacteria contain the sequence for a small protein with a common “Domain of Unknown Function” grouped into the DUF683 protein family. While the biological function of DUF683 is still not known, their genomic location within nitrogen fixation clusters suggests that DUF683 proteins may play a role in the process. The diurnal cyanobacterium Cyanothece sp. PCC 51142 contains a gene for a protein that falls into the DUF683 family, cce_0567 (78 aa, 9.0 kDa). In an effort to elucidate the biochemical role DUF683 proteins may play in nitrogen fixation, we have determined the first crystal structure for a protein in this family, cce_0567, to 1.84 Å resolution. Cce_0567 crystallized in space group P2(1) with two protein molecules and one Ni(2+) cation per asymmetric unit. The protein is composed of two α-helices, residues P11 to G41 (α1) and L49–E74 (α2), with the second α-helix containing a short 3(10)-helix (Y46–N48). A four-residue linker (L42–D45) between the helices allows them to form an anti-parallel bundle and cross over each other towards their termini. In solution it is likely that two molecules of cce_0567 form a rod-like dimer by the stacking interactions of ~1/2 of the protein. Histidine-36 is highly conserved in all known DUF683 proteins and the N2 nitrogen of the H36 side chain of each molecule in the dimer is coordinated with Ni(2+) in the crystal structure. The divalent cation Ni(2+) was titrated into (15)N-labeled cce_0567 and chemical shift perturbations were observed only in the (1)H–(15)N HSQC spectra for residues at, or near, the site of Ni(2+) binding observed in the crystal structure. There was no evidence for an increase in the size of cce_0567 upon binding Ni(2+), even in large molar excess of Ni(2+), indicating that a metal was not required for dimer formation. Circular dichroism spectroscopy indicated that cce_0567 was extremely robust, with a melting temperature of ~62 °C that was reversible