Molecules In Asymmetric Unit Research Articles

Synthesis of a new hydrazone-based schiff base: Spectroscopy, single crystal, DNA binding and theoretical studies

A new thiosemicarbazide-based Schiff base (TSDHB) was synthesized from thiosemicarbazide and 2,3-dihydroxybenzaldehyde. The prepared thiosemicarbazone was characterized by elemental (CHN), FT-IR, 1H and 13C NMR techniques. Furthermore, the molecular structure was probed using the single-crystal X-ray diffraction (SC-XRD) technique, which confirmed the enol tautomeric form with two independent molecules in asymmetric unit. The dissimilarity between the molecular units was determined by molecular overlay plots. The various intermolecular interactions and solid-state assembly stabilization were explored by Hirshfeld surface analysis. Void analysis was executed to examine the mechanical stability of crystalline units. The bioactivity of thiosemicarbazone was probed with the help of its binding capacity with salmon sperm DNA (SS-DNA) by means of the absorption interaction method. Accompanied by biological activity, optoelectronic properties such as nonlinear optical properties of yielded crystal were also explored through the DFT approach at M06/6–311 G (d,p). For this, various kinds of investigations such as frontier molecular orbital (FMO), UV–Vis, global reactivity parameters (GRPs), transition density matrix (TDM), density of states (DOS), natural population analysis (NPA), and natural bond orbital analysis (NBO) were executed at M06 functional. A good agreement was examined between XRD and DFT findings of molecular geometric parameters. Notably, in comparison with urea, TSDHB demonstrated enhanced nonlinear optical properties (linear polarizability=4.766 × 10−23esu and third-order hyperpolarizability=5.939 × 10−35esu). These findings position TSDHB as a promising candidate for DNA binding as well as for photonic materials due to its unique molecular characteristics and enhanced nonlinear optical behavior.

Heteroleptic Copper(I) complexes of bipyridine glycoluril and phosphine ligands: Photophysical and computational studies

A series of heteroleptic copper(I) complexes of the type [Cu(bpg)(PP)]PF6 (1–4) have been synthesized where bpg = [4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f] [1,10]-phenanthroline-6,13-dione] and PP are phosphine derived ancillary ligands (triphenyl phosphine (PPh3), 1,2 bis(diphenylphosphino)ethane (dppe), bis[(2-diphenylphosphino)phenyl]ether (POP) and 1,3 bis(diphenylphosphino)propane (dppp)). All copper(I)-phosphine complexes were thoroughly characterized by elemental analyses, IR, 1H NMR, 13C NMR, 31P NMR and ESI-MS, UV–visible, emission spectroscopy and DFT calculations. The crystal structure of 1 contains two Cu(I) molecules in asymmetric unit which localizes in distorted tetrahedral geometry with N2P2 coordination core. The UV–visible spectra indicated that ancillary phosphine ligands significantly affect the MLCT band of the copper(I) complexes. The bands in the UV–visible spectra fit well with the TD-DFT calculations and are assigned to the contribution of HOMO-2 → LUMO, HOMO-1 → LUMO and HOMO → LUMO orbitals. These Cu(I) complexes exhibit green emission in CH2Cl2 at room temperature with emission wavelengths at 545–572 nm. Cyclic voltammetric data revealed that steric hindrance of diphosphine ligands affected the oxidation potential of Cu(I) complexes.

Crystal structure and characterization of nucleoside diphosphate kinase from Vibrio cholerae

Nucleoside diphosphate kinases (NDK) are ubiquitous enzymes that catalyse the transfer of the γ phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphate (NDPs), to maintain appropriate NTP levels in cells. NDKs are associated with signal transduction, cell development, proliferation, differentiation, tumor metastasis, apoptosis and motility. The critical role of NDK in bacterial virulence renders it a potential drug target. The present manuscript reports crystal structure and functional characterization of Vibrio cholerae NDK (VNDK). The 16 kDa VNDK was crystallized in a solution containing 30% PEG 4000, 100 mM Tris-HCl pH 8.5 and 200 mM sodium acetate in orthorhombic space group P212121 with unit cell parameters a = 48.37, b = 71.21, c = 89.14 Å, α = β = γ = 90° with 2 molecules in asymmetric unit. The crystal structure was solved by molecular replacement and refined to crystallographic Rfactor and Rfree values of 22.8% and 25.8% respectively. VNDK exists as both dimer and tetramer in solution as confirmed by size exclusion chromatography, glutaraldehyde crosslinking and small angle X-ray scattering while the crystal structure appears to be a dimer. The biophysical characterization states that VNDK has kinase and DNase activity with maximum stability at pH 8–9 and temperature up to 40 °C. VNDK shows elevated thermolability as compared to other NDK and shows preferential binding with GTP rationalized using computational studies.

Dimethyl 3,3'-[(4-nitro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate) ethanol hemisolvate.

There are two main molecules in asymmetric unit of the title compound, C27H21N3O6·0.5C2H5OH. In both, the indole ring systems are approximately perpendicular to each other, at dihedral angles of 69.3 (5) and 82.8(4)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional supra-molecular architecture. The solvent ethanol mol-ecule acts as a donor, forming an O-H⋯O hydrogen bond, reinforcing the structure.

Polymorphic modifications of a 1H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide possessing strong diuretic properties.

6-Hydroxy-N-(4-methoxyphenyl)-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide, C19H16N2O4, possesses strong diuretic properties and can be used as a new hypertension remedy. Two polymorphic modifications of this compound have been found, namely the triclinic polymorph (space group P-1), with one molecule in the asymmetric unit, and the monoclinic polymorph (space group P21/n), with two molecules in asymmetric unit. An analysis of the pairwise interaction energies between the molecules in the crystal phase revealed differences in the crystal packing. The triclinic form has only one level of organization, namely a chain/column, while the monoclinic form has two levels of organization, with a chain/column as the primary basic structural motif and a layer as the secondary basic structural motif.

Synthesis, single crystal X-ray diffraction, Hirshfeld surface and biological activity of quinolone derivatives

Two new quinolone derivatives, 5-nitroquinolin-8-yl-3-bromobenzoate (1) and 5-nitroquinolin-8-yl-3-chlorobenzoate (2), were synthesized and their structures were elucidated using X-ray diffraction techniques. Both compounds crystallized in P 2 1 / n (monoclinic) space group having four independent molecules in asymmetric unit. The dihedral angle between benzene and planner quinoline rings in compounds 1 and 2 were found to be 117.7(2) and 117.4(2)ᵒ, respectively. No intermolecular hydrogen bonding was observed in compound 1. However, C-H···O intermolecular interaction was found to connect the molecules in crystal lattice of compound 2. Hirshfeld surfaces analysis was performed to evaluate the directions, and strength of interactions of molecules of compounds and 1 and 2 with neighbouring molecules, and the major contribution in the crystal packing was due to O-H (1, 24.6% and 2, 25.1%) interactions. The synthesized quinoline derivatives were found as potent anti-bacterial agents against E. coli reference (ATCC25922 and ATCC 35218) and multi-drug resistant strains (M2 and M3) with 91.42 to 94.72% inhibition. Both compounds 1 and 2 showed weak antileishmanial activity against L. Major promastigotes in vitro with IC 50 values 73.2±3.1 and 72.2±2.3 mg/mL, respectively, and also found as cytotoxic in nature against 3T3 fibroblast cell line.

Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from Mycobacterium tuberculosis

The biosynthesis of UDP-N-acetylmuramic acid (UDP-MurNAc) by reduction of UDP-N-acetylglucosamine-enolpyruvate (UDP-GlcNAc-EP) in an NADPH and FAD-dependent reaction in bacteria is one of the key steps in peptidoglycan biosynthesis catalyzed by UDP-N-acetylglucosamine-enolpyruvate reductase (MurB). Here, we present the crystal structure of Mycobacterium tuberculosis MurB (MtbMurB) with FAD as the prosthetic group at 2.0Å resolution. There are six molecules in asymmetric unit in the form of dimers. Each protomer can be subdivided into three domains and the prosthetic group, FAD is bound in the active site between domain I and domain II. Comparison of MtbMurB structure with the structures of the Escherichia coli MurB (in complex with UDP-GlcNAc-EP) and Pseudomonas aeruginosa MurB (in complex with NADPH) showed all three structures share similar domain architecture and residues in the active site. The nicotinamide and the enol pyruvyl moieties are well aligned upon superimposition, both positioned in suitable position for hydride transfer to and from FAD. The comparison studies and MD simulations demonstrate that the two lobes of domain-III become more flexible. The substrates (NADPH and UDP-GlcNAc-EP) binding responsible for open conformation of MurB, suggesting that NADPH and UDP-GlcNAc-EP interactions are conformationally stable. Our findings provide a detail mechanism about the closed to open state by binding of NADPH and UDP-GlcNAc-EP induces the conformational changes of MurB structure that may trigger the MurB catalytic reaction.

Polymorphism involving multiple molecules in asymmetric unit of trifluoromethylated phenylbenzamide

Polymorphism involving multiple molecules in asymmetric unit of trifluoromethylated phenylbenzamide

Synthesis, characterization, crystal structures and DFT studies of some new 1,2,4-triazole and triazolidin derivatives

A simple efficient method for synthesis of some new 1,2,4-Triazole and Triazolidin derivatives namely, 5-(4-methoxyphenyl)-2-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (1a), (2-chlorophenyl)(3,3-dimethyl-1-phenyl-5-thioxo-1,2,4-triazolidin-4-yl)methanone (1b) and (2-iodophenyl)(3,3-dimethyl-1-phenyl-5-thioxo-1,2,4-triazolidin-4-yl)methanone (1c) have been synthesized in high yields from the reaction of carbonoyl isothiocyanate with phenyl hydrazine. The final products were characterized by FT-IR, 1H and 13C NMR spectroscopic techniques. X-ray crystallographic studies showed that 1a crystallized in triclinic crystal system with space group Pī, while both 1b and 1c crystallized in orthorhombic crystal system with space group Pna21. The asymmetric unit of 1a consists two crystallographically independent molecules, while only one molecule in asymmetric unit for both 1b and 1c compounds. All molecules possess CH ….S intramolecular hydrogen bonds which formed a pseudo-six-membered ring. Experimental results have been confirmed by the state-of-art density functional theory (DFT) in gas and solvent phase by using five different hybrid functionals B3LYP, B3P86, CAM-B3LYP, M06-2X and PBE0 combined with 6–311++G(d, p) basis set. The experimental data are relatively well produced, and relatively good correlations are obtained between the predicted and experimental data.

Experimental (X-ray, IR and UV–vis.) and DFT studies on cocrystallization of two tautomers of a novel Schiff base compound

In this study, the structure of 4-(((2-methyl-3-nitrophenyl)imino)methyl)benzene-1,2,3-triol was investigated with experimental (X-ray single crystal technique, UV–vis. and FT-IR spectroscopic techniques) and theoretical (DFT) methods. X-ray studies show that there are two independent molecules in asymmetric unit and coexist both keto-amin and enol-imine tautomeric forms. Theoretical studies were carried out in B3LYP with CAM-631G(d,p). The data obtained from calculation were compared with experimental data.

Crystal structure of (E)-3-fluoro-N-((5-nitrothiophen-2-yl)methylene)aniline

The structure of the title compound C11H7FN2O2S was characterized by single crystal X-ray diffraction. The compound crystallizes in the monoclinic space group P21/n with Z = 12, i.e. with three molecules in asymmetric unit. The molecules are not planar: the dihedral angles between the planes of thiophene and the benzene rings are 42.3(3)°, 42.0(3)°, and 48.9(2)°. In the crystal, intermolecular C–H···F interactions link the molecules through R22 (14) ring motif. The crystal packing is also stabilized by π···π interactions.

Imine-tautomers of aminothiazole derivatives: intriguing aspects of chemical reactivities

Intriguing reactivities of positional isomers 1-(5-methylthiazol-2-yl)-3-(4-nitrophenyl)thiourea (L1) and 1-(4-methylthiazol-2-yl)-3-(4-nitrophenyl)thiourea (L2) towards environment polluting ions such as mercuric, fluoride, bromide and solvents provide scope to study various self-assemblies formed under different conditions and allied applications. The solid state structures of L1 and L2 revealed that both adopt the imine form. However, the number of symmetry independent molecules in asymmetric units as well as the packing patterns of these two compounds have distinguishable features. The asymmetric unit of L1 has three symmetry non-equivalent molecules. The packing patterns of these two positional isomers differ as L1 has two arrays of dimeric self-assemblies in contrast to the single array found in the packing of L2. The reactivity of L1 and L2 with solvents was explored through crystal structure elucidation. The compound L1 forms solvates with N,N′-dimethylacetamide or dimethylsulphoxide. The structural analysis of solvates of L1 provided avenues to study conformational adjustments. An unusual example of a metastable solvate of L1 with N,N′-dimethylacetamide was isolated. A ring-opening reaction of 1,8-diazabicyclo [5.4.0] undec-7-ene with L1 has been observed. The compound L2 underwent hydrolysis cum bromination with hydrobromic acid in dimethylsulphoxide. The reactivities of L1 and L2 towards mercuric and fluoride ions contributed to chemodosimetric signal transductions. The study establishes the impact of subtle changes in structure, reaction and crystallization conditions, which can influence pre-designed crystal engineering.

Synthesis and proton conductivity of azole-substituted cyclic and polymeric phosphazenes

In this paper we describe the synthesis, characterization and proton conductivity of azole-substituted cyclic and polymeric phosphazenes. All of the cyclic compounds HTCP, OTCP and polymer, PVTP were fully characterized by elemental analysis, FT-IR, 1H, 13C and 31P NMR spectroscopy. Thermal properties of newly synthesized compounds were investigated with TGA&DSC and the anhydrous proton conductivity was measured by impedance spectroscopy at selected temperatures. It was found that, maximum proton conductivity of 0.043 S cm−1 was obtained for PVTP, which is doped with trifluoromethane sulfonic acid, at 150 °C without decomposition. The cyclic derivative HTCP has been obtained as triclinic crystals in P − 1 space group with two water molecules in asymmetric unit. The X-ray structural characterization result supported that the proton transfer has been ensured by Grotthuss mechanism.

Multiple Molecules in the Crystallographic Asymmetric Unit of (Z)-3-(3-Chlorophenyl)-2-phenyl acrylic acid

The title compound, (Z)-3-(3-chlorophenyl)-2-phenyl acrylic acid (C15H11ClO2), crystallizes in the monoclinic space group P21 with the following unit-cell parameters: a = 18.7975(12), b = 15.3248(9), c = 24.378(2)A, β = 108.058(8)° and Z = 20. The crystal structure was solved by direct methods and refined by full-matrix least-squares procedures to a final R-value of 0.0781 for 8174 observed reflections. The molecule consists of two phenyl rings and an acrylic unit. In this structure there are ten crystallographically independent molecules in the asymmetric unit. Apparently, some minor differences in the conformations of these molecules in the asymmetric units could lead to different hydrogen-bond motifs. The crystal structure contains intermolecular O-H…O and C-H…π hydrogen bonds. The minimum π-π distance is 4.864(6)A.

Crystal structures of the all-cysteinyl-coordinated D14C variant of Pyrococcus furiosus ferredoxin: [4Fe–4S] ↔ [3Fe–4S] cluster conversion

The structure of the all-cysteinyl-coordinated D14C variant of [4Fe-4S] ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus has been determined to 1.7Å resolution from a crystal belonging to space group C222(1) with two types of molecules, A and B, in the asymmetric unit. A and B molecules have different crystal packing and intramolecular disulfide bond conformation. The crystal packing reveals a β-sheet interaction between A molecules in adjacent asymmetric units, whereas B molecules are packed as monomers in a less rigid position next to the A-A extended β-sheet dimers. The A molecules contain an intramolecular disulfide bond in a double conformation with 60% occupancy left-handed and 40% occupancy right-handed spiral conformation, whereas B molecules have an intramolecular disulfide bond in a right-handed spiral conformation. The cluster in D14C [4Fe-4S] P. furiosus ferredoxin was chemically oxidized at pH 5.8 to [3Fe-4S]. For purification at pH 8.0, two forms of the protein are obtained. Mass spectrometric analysis shows that the two forms are the D14C [3Fe-4S] P. furiosus ferredoxin monomer and a disulfide-bonded dimer of D14C [3Fe-4S] P. furiosus ferredoxin. When oxidization and purification are carried out at pH 5.8, only the monomer is obtained. The crystal structure of D14C [3Fe-4S] P. furiosus ferredoxin monomer was determined to 2.8Å resolution from a crystal belonging to space group P2(1)2(1)2(1) with two molecules in the asymmetric unit. The molecules resemble molecule A of D14C [4Fe-4S] P. furiosus ferredoxin and electron density clearly shows the presence of a [3Fe-4S] cluster.

Synthesis and molecular structure of the all-trans- and the trans–cis-isomers of dichlorodimethyltin complexes of phosphoric triamides

Four new phosphoramidates with formula 4-RC6H4C(O)NHP(O)(NH(CH(CH3)2)2, R=H (1), OCH3 (2), CH3 (3), Cl (4) and their diorganotin(IV) complexes with formula SnCl2(CH3)2(X)2, X=1 (5), 2 (6), 3 (7) and 4 (8) were synthesized and characterized by NMR, IR spectroscopy and elemental analysis. The spectroscopic properties of complexes were compared with those corresponding ligands. The molecular structures for 5, 5·CH3CN, 6·CH3CN, 7 and 8 were established by X-ray diffraction analysis and shown that the tin atoms have a distorted octahedral coordination with trans-methyl groups. Two different all-trans and cis–trans isomers were obtained by changing the crystallization solvent system. The existence of CH3CN in molecular packing of trans–cis isomers might be a packing factor governing the orientation of the ligands. Due to the presence of several hydrogen bond donors and acceptors on compounds, extended hydrogen-bonded networks were observed. The structure of 2 was also determined and possesses two crystallographically independent molecules in asymmetric unit. On forming complex 6·CH3CN, the ligand 2 shows shortening of CO and P–N bond distances and increasing of PO bond length. Pseudopolymorphism of diorganotins in 5 and 5·CH3CN is reported for the first time.

Emerging from pseudo-symmetry: the redetermination of human carbonic anhydrase II in monoclinicP21with a doubledaaxis

The crystal structure of human carbonic anhydrase II in the monoclinic P2(1) space group with a doubled a axis from that of the usually observed unit cell has recently been reported, with one of the two molecules in the asymmetric unit demonstrating rotational disorder [Robbins et al. (2010), Acta Cryst. D66, 628-634]. The structure has been redetermined, with the coordinates of both pseudo-symmetrically related molecules in the crystallographic asymmetric unit translated by x' = x +/- 1/4, and no rotational disorder is observed. This corresponds to a different choice of how the four molecules in the unit cell should be grouped into pairs that represent a single asymmetric unit.

On the Relevance of the Met-turn Methionine in Metzincins

The metzincins are a clan of metallopeptidases consisting of families that share a series of structural elements. Among them is the Met-turn, a tight 1,4-turn found directly below the zinc-binding site, which is structurally and spatially conserved and invariantly shows a methionine at position 3 in all metzincins identified. The reason for this conservation has been a matter of debate since its discovery. We have studied this structural element in Methanosarcina acetivorans ulilysin, the structural prototype of the pappalysin family, by generating 10 mutants that replaced methionine with proteogenic amino acids. We compared recombinant overexpression yields, autolytic and tryptic activation, proteolytic activity, thermal stability, and three-dimensional structure with those of the wild type. All forms were soluble and could be purified, although with varying yields, and three variants underwent autolysis, could be activated by trypsin, and displayed significant proteolytic activity. All variants were analyzed for the thermal stability of their zymogens. None of the mutants analyzed proved more stable or active than the wild type. Both bulky and small side chains, as well as hydrophilic ones, showed diminished thermal stability. Two mutants, leucine and cysteine, crystallized and showed three-dimensional structures that were indistinguishable from the wild type. These studies reveal that the Met-turn acts as a plug that snugly inserts laterally into a core structure created by the protein segment engaged in zinc binding and thus contributes to its structural integrity, which is indispensable for function. Replacement of the methionine with residues that deviate in size, side-chain conformation, and chemical properties impairs the plug-core interaction and prejudices molecular stability and activity.

Crystal structure of human retinoblastoma binding protein 9

Crystal structure of human retinoblastoma binding protein 9

Structure of the Human Lung Cytochrome P450 2A13

The human lung cytochrome P450 2A13 (CYP2A13) activates the nicotine-derived procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) into DNA-altering compounds that cause lung cancer. Another cytochrome P450, CYP2A6, is also present in human lung, but at much lower levels. Although these two enzymes are 93.5% identical, CYP2A13 metabolizes NNK with much lower K(m) values than does CYP2A6. To investigate the structural differences between these two enzymes the structure of CYP2A13 was determined to 2.35A by x-ray crystallography and compared with structures of CYP2A6. As expected, the overall CYP2A13 and CYP2A6 structures are very similar with an average root mean square deviation of 0.5A for the Calpha atoms. Like CYP2A6, the CYP2A13 active site cavity is small and highly hydrophobic with a cluster of Phe residues composing the active site roof. Active site residue Asn(297) is positioned to hydrogen bond with an adventitious ligand, identified as indole. Amino acid differences between CYP2A6 and CYP2A13 at positions 117, 300, 301, and 208 relate to different orientations of the ligand plane in the two protein structures and may underlie the significant variations observed in binding and catalysis of many CYP2A ligands. In addition, docking studies suggest that residues 365 and 366 may also contribute to differences in NNK metabolism.