Structural variety of heterosynthons in linezolid cocrystals with modified thermal properties.

In a search for new crystalline forms of linezolid with modified thermal properties five cocrystals of this wide range antibiotic with aromatic acids were obtained via mechanochemical grinding and analyzed with single crystal X-ray diffraction, solid-state NMR spectroscopy, powder X-ray diffraction and DSC measurements. The coformers used in this study were benzoic acid, p-hydroxybenzoic acid, protocatechuic acid, γ-resorcylic acid and gallic acid. In each of the cocrystals distinct structural features have been found, including a variable amount of water and different heterosynthons, indicating that there is more than one type of intermolecular interaction preferred by the linezolid molecule.

Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals.

Two, well defined binary crystals with 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide (HIMO) as coformer and thiobarbituric acid (TBA) as well barbituric acid (BA) as Active Pharmaceutical Ingredients (APIs) were obtained by cocrystallization (from methanol) or mechanochemically by grinding. The progress of cocrystal formation in a ball mill was monitored by means of high-resolution, solid state NMR spectroscopy. The C CP/MAS, N CP/MAS and H Very Fast (VF) MAS NMR procedures were employed to inspect the tautomeric forms of the APIs, structure elucidation of the coformer and the obtained cocrystals.

New synthetic pathway leading to oxospirochlorins.

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels-Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates.

Crystal and molecular structure of hexagonal form of lipase B from Candida antarctica.

During crystallization screenings of commercially available hydrolytic enzymes, the new, hexagonal crystal form of CAL-B, has been discovered and hereby reported. The NAG molecules, which were closing the glycosylation site in the orthorhombic form, in hexagonal structure make the glycosylation site open. It is unknown whether the opening and closing of the glycosylation site by the 'lid' NAG molecules, could be related to the opening and closing of the active center of the enzyme upon substrate binding and product release.

Expression, purification, crystallization and preliminary X-ray crystallographic analysis of human histidine triad nucleotide-binding protein 2 (hHINT2).

Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial adenosine phosphoramidase mainly expressed in the pancreas, liver and adrenal gland. HINT2 possibly plays a role in apoptosis, as well as being involved in steroid biosynthesis, hepatic lipid metabolism and regulation of hepatic mitochondria function. The expression level of HINT2 is significantly down-regulated in hepatocellular carcinoma patients.

The influence of the stereochemistry of alanine residue on the solid state conformation and crystal packing of opioid peptides containing D-Ala or L-Ala in message domain--XRD and NMR study.

In this work, an X-ray diffraction (XRD) and solid state NMR study of two tetrapeptides with different stereochemistry of alanine residue is presented using Tyr-(D-Ala)-Phe-Gly (1), an N-terminal sequence of opioid peptide dermorphin, and its biologically inactive analog Tyr-(L-Ala)-Phe-Gly (2). Single-crystal XRD proved that 1 crystallized under different conditions from exclusively one structure: a monoclinic crystal with P2(1) space group. In contrast, 2 very easily formed at least three crystallographic modifications, 2a (monoclinic P2(1)), 2b (orthorhombic P2(1)2(1)2) and 2c (tetragonal P4(1)2(1)2).

Study of host-guest interactions in benzodiazacoronands by means of solid state NMR spectroscopy, X-ray diffraction and quantum mechanical computations.

In this work we present solid state data for five host-guest complexes formed by N-(4,19-dioxo-2,8,15,21-tetraoxa-5,18-diazatricyclohexacosa-1(25),9(14),10,12,22(26),23-hexaen-26-yl)-benzamide (1) belonging to the group of benzodiazacoronands, achiral compounds for which chiral crystals were found (J. Kalisiak and J. Jurczak, Cryst.

Structural investigation of biologically active phenolic compounds isolated from European tree species.

X-ray structures of two compounds isolated from wood knots of coniferous trees, namely dihydrokaempferol (3,5,8,13-tetrahydroxyflavanon) and lariciresinol (3,14-dimetoxy-7,10-epoxylignan-4,15,19-triol), are presented here. Diffraction data for the Dihydrokaempferol crystals were collected on a CAD4 diffractometer and on a synchrotron for the lariciresinol crystal. The investigated compounds inhibit lipid peroxidation and lariciresinol is additionally a good scavenger of superoxide radicals.

Synthesis and solid-state study of supramolecular host-guest assemblies: Bis[6-O,6-O'-(1,2:3,4-diisopropylidene-alpha-D-galactopyranosyl)thiophosphoryl] dichalcogenides.

A complementary approach for studying structural details of complex solid materials formed by symmetrical and unsymmetrical dichalcogenides, which employs both X-ray diffraction (XRD) and solid-state NMR (SS NMR), is presented. The new diagnostic technique allows reversible crystallographic space group change and very subtle distortion of host geometry to be followed during guest migration in the crystal lattice. Bis[6-O,6-O'-(1,2:3,4-diisopropylidene-alpha-D-galactopyranosyl)]thiophosphoryl selenenyl sulfide, a representative of wheel-and-axle host (WAAH) molecules, can be synthesized in the solid state by grinding and gentle heating of disulfide 1 and diselenide 2.

Structural basis of the sulphate starvation response in E. coli: crystal structure and mutational analysis of the cofactor-binding domain of the Cbl transcriptional regulator.

Cbl is a member of the large family of LysR-type transcriptional regulators (LTTRs) common in bacteria and found also in Archaea and algal chloroplasts. The function of Cbl is required in Escherichia coli for expression of sulphate starvation-inducible (ssi) genes, associated with the biosynthesis of cysteine from organic sulphur sources (sulphonates). Here, we report the crystal structure of the cofactor-binding domain of Cbl (c-Cbl) from E.

Crystal structure of Vigna radiata cytokinin-specific binding protein in complex with zeatin.

The cytosolic fraction of Vigna radiata contains a 17-kD protein that binds plant hormones from the cytokinin group, such as zeatin. Using recombinant protein and isothermal titration calorimetry as well as fluorescence measurements coupled with ligand displacement, we have reexamined the K(d) values and show them to range from approximately 10(-6) M (for 4PU30) to 10(-4) M (for zeatin) for 1:1 stoichiometry complexes. In addition, we have crystallized this cytokinin-specific binding protein (Vr CSBP) in complex with zeatin and refined the structure to 1.

Study of molecular dynamics and the solid state phase transition mechanism for unsymmetrical thiopyrophosphate using X-ray diffraction, DFT calculations and NMR spectroscopy.

Differential scanning calorimetry (DSC) and low-temperature X-ray diffraction studies showed that 2-thio-(5,5-dimethyl-1,3,2-dioxaphosphorinanyl)2'-oxo-dineopentyl-thiophosphate (compound 1) undergoes reversible phase transition at 203 K related to the change of symmetry of the crystallographic unit. Solid state NMR spectroscopy was used to establish the dynamic processes of aliphatic groups and the phosphorus skeleton. 13C and 31P variable temperature NMR studies as well as T1 and T1rho measurements of relaxation times revealed the different mode of molecular motion for each neopentyl residue directly bonded to phosphorus.

Crystallization and preliminary crystallographic studies of the cofactor-binding domain of the LysR-type transcriptional regulator Cbl from Escherichia coli.

Cbl (CysB-like protein) is a member of the family of LysR-type transcriptional regulators (LTTRs) and controls genes engaged in sulfur assimilation in Escherichia coli. It has been postulated that adenosine 5-phosphosulfate (APS) is responsible for abolishing Cbl-activated transcription from the ssu promoter (Bykowski et al., 2002).

Coordination properties of tris(2-carboxyethyl)phosphine, a newly introduced thiol reductant, and its oxide.

Acid-base properties and metal-binding abilities of tris(2-carboxyethyl)phosphine (TCEP), a newly introduced thiol group protectant, were studied in solution, using potentiometry, (1)H and (31)P NMR, and UV-vis spectroscopy, and also in the solid state by X-ray diffraction. Stability constants of complexes of the P-oxide of TCEP (TCEPO) were established by potentiometry. The list of metal ions studied included Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II).

Crystallization and preliminary crystallographic studies of mung bean cytokinin-specific binding protein.

Cytokinins, or plant growth hormones, bind with very high affinity to cytokinin-specific binding proteins (CSBPs). Recombinant mung bean CSBP has been overexpressed in Escherichia coli and crystallized in complex with zeatin, a natural plant growth hormone. The crystals belong to the hexagonal system, space group P6(2) or P6(4), with unit-cell parameters a = 113.