2-Chloro-7,8-dimethylquinoline-3-carbaldehyde

All the non-H atoms of the title compound, C12H10ClNO, lie on a crystallographic mirror plane orientated perpendicular to the crystallographic b axis.

2-Chloro-7-methylquinoline-3-carbaldehyde

The quinoline fused-ring system of the title compound, C11H8ClNO, is planar (r.m.s. deviation = 0.007 angstrom); the formyl group is bent slightly out of the plane [C-C-C-O torsion angles = -9.6 (5) and 170.4 (3)degrees].

The alpha method for solving differential algebraic inequality (DAI) systems

This paper describes an algorithm for ``direct numerical integration'' of the initial value Differential-Algebraic Inequalities (DAI) in a time stepping fashion using a sequential quadratic programming (SQP) method solver for detecting and satisfying active path constraints at each time step. The activation of a path constraint generally increases the condition number of the active discretized differential algebraic equation's (DAE) Jacobian and this difficulty is addressed by a regularization property of the alpha method. The algorithm is locally stable when index 1 and index 2 active path constraints and bounds are active. Subject to available regularization it is seen to be stable for active index 3 active path constraints in the numerical examples. For the high index active path constraints, the algorithm uses a user-selectable parameter to perturb the smaller singular values of the Jacobian with a view to reducing the condition number so that the simulation can proceed. The algorithm can be used as a relatively cheaper estimation tool for trajectory and control planning and in the context of model predictive control solutions. It can also be used to generate initial guess values of optimization variables used as input to inequality path constrained dynamic optimization problems. The method is illustrated with examples from space vehicle trajectory and robot path planning.

Ring Expansion of Oxyglycals. Synthesis and Conformational Analysis of Septanoside-Containing Trisaccharides

Oxyglycals, derived from lactose and maltose, were expanded to trisaccharides through a ring expansion method. Trisaccharides with 6-7-5 and 6-7-6 ring sizes were prepared through the ring expansion method, with high diastereoselectivities, in each step of their synthesis. The NOE and ROESY NMR spectroscopies were used to assess the dipolar Couplings within the trisaccharide. A computational study was undertaken, from which low energy conformations, as well as, dihedral angles that define the glycosidic linkages were identified.

2-Chloro-3-hydroxymethyl-7,8-dimethylquinoline

All non-H atoms of the title compound, C12H12ClNO, are co-planar (r.m.s. deviation = 0.055 angstrom). The hydroxy H atom is disordered over two positions of equal occupancy. In the crystal, molecules are linked by O-H center dot center dot center dot O hydrogen bonds, generating zigzag chains running along the b axis.

Photocytotoxic Oxovanadium(IV) Complexes Showing Light-Induced DNA and Protein Cleavage Activity

Oxovanadium(IV) complexes [VO(L)(B)]Cl-2 (1-3), where L is bis(2-benzimidazolylmethyl)amine and B is 1,10-phenanthroline(phen),dipyrido[3,2-d:2',3'-f]quinoxaline(dpq) or dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been prepared, characterized, and their photo-induced DNA and protein cleavage activity studied. The photocytotoxicity of complex 3 has been studied using adenocarcinoma A549 cells, The phen complex 1, structurally characterized by single-crystal X-ray crystallography, shows the presence of a vanadyl group in six-coordinate VON5 coordination geometry. The ligands L and phen display tridentate and bidentate N-donor chelating binding modes, respectively. The complexes exhibit a d-d band near 740 nm in 15% DMF-Tris-HCl buffer (pH 7.2). The phen and dpq complexes display an irreversible cathodic cyclic voltammetric response near -0.8 V in 20% DMF-Tris-HCl buffer having 0.1 M KCl as supporting electrolyte. The dppz complex 3 exhibits a quasi-reversible voltammogram near -0.6 V (vs SCE) that is assignable to the V(IV)-V(III)couple. The complexes bind to calf thymus DNA giving binding constant values in the range of 6.6 x 10(4)-2.9 x 10(5) M-1. The binding site size, thermal melting and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor ``chemical nuclease'' activity in dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A light of 365 nm via a mechanistic pathway that involves formation of both singlet oxygen and hydroxyl radicals. The complexes show significant photocleavage of DNA in near-IR light (>750 nm) via hydroxyl radical pathway. Among the three complexes, the dppz complex 3 shows significant BSA and lysozyme protein cleavage activity in UV-A light of 365 nm via hydroxyl radical pathway. The dppz complex 3 also exhibits photocytotoxicity in non-small cell lung carcinoma/human lung adenocarcinoma A549 cells giving IC50 value of 17 mu M in visible light(IC50 = 175 mu M in dark).

2-[(E)-(4-hydroxy-3-methoxybenzylidene)amino]-N-(2-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

The title compound, C24H24N2O3S, exhibits antifungal and antibacterial properties. The compound crystallizes with two molecules in the asymmetric unit, with one molecule exhibiting 'orientational disorder' in the crystal structure with respect to the cyclohexene ring. The o-toluidine groups in both molecules are noncoplanar with the respective cyclohexene-fused thiophene ring. In both molecules, there is an intramolecular N-H...N hydrogen bond forming a pseudo-six-membered ring which locks the molecular conformation and eliminates conformational flexibility. The crystal structure is stabilized by O-H...O hydrogen bonds; both molecules in the asymmetric unit form independent chains, each such chain consisting of alternating 'ordered' and 'disordered' molecules in the crystal lattice.

6,8-Dibromo-5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl acetate

In the title compound, C17H10Br2O5, the chromene ring is almost planar with minimal puckering [total puckering amplitude = 0.067 (4) angstrom]. The dihedral angle between chromeme ring system and phenyl ring is 3.7 (2)degrees. The crystal structure is stabilized by intermolecular C-H center dot center dot center dot O interactions and an intramolecular O-H center dot center dot center dot O hydrogen bond also occurs.

Oxovanadium(IV) complexes of phenanthroline bases: the dipyridophenazine complex as a near-IR photocytotoxic agent

Oxovanadium(IV) complexes [VOCl(B)(2)]Cl (1-3) of phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d: 2', 3'-f] quinoxaline (dpq in 2) and dipyrido[3,2-a: 2', 3'-c] phenazine (dppz in 3), have been prepared, characterized and their DNA and protein binding, photo-induced DNA and protein cleavage activity andm photocytotoxicity have been studied. Complex 2, structurally characterized by X-ray crystallography, shows the presence of a vanadyl group in VOClN4 coordination geometry. The dpq ligand displays a chelating mode of binding with a N-donor site trans to the oxo-group. The chloride ligand is cis to the oxo-group. The one-electron paramagnetic complexes show a d-d band near 715 nm in 15% DMF-Tris-HCl buffer. The complexes are redox active exhibiting a V(IV)/V(III) redox couple within -0.5 to -0.7 V vs. SCE in 20% DMF-Tris-HCl/0.1 M KCl. The complexes bind to calf thymus (CT) DNA in the order: 3 (dppz) > 2 (dpq) > 1 (phen). The binding data reveal the groove and/or partial intercalative DNA binding nature of the complexes. The complexes show chemical nuclease'' activity in the dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide via a hydroxyl radical pathway. The dpq and dppz complexes are efficient photocleavers of DNA in UV-A light of 365 nm forming reactive singlet oxygen (O-1(2)) and hydroxyl radical ((OH)-O-center dot) species. Complexes 2 and 3 also show DNA cleavage activity in red light (> 750 nm) by an exclusive (OH)-O-center dot pathway. The complexes display a binding propensity to bovine serum albumin (BSA) protein giving K-BSA values in the range of 7.1 x 10(4)-1.8 x 10(5) M-1. The dppz complex 3 shows BSA and lysozyme protein cleavage activity in UV-A light of 365 nm via (OH)-O-center dot pathway. The dppz complex 3 exhibits significant PDT effect in human cervical cancer HeLa cells giving IC50 values of 1.0 mu M and 12.0 mu M in UV-A and visible light, respectively (IC50 = > 100 mu M in the dark).

A one-step technique to prepare aligned arrays of carbon nanotubes

A simple effective pyrolysis technique has been developed to synthesize aligned arrays of multi-walled carbon nanotubes (MWCNTs) without using any carrier gas in a single-stage furnace at 700 °C. This technique eliminates nearly the entire complex and expensive machinery associated with other extensively used methods for preparation of CNTs such as chemical vapour deposition (CVD) and pyrolysis. Carbon source materials such as xylene, cyclohexane, camphor, hexane, toluene, pyridine and benzene have been pyrolyzed separately with the catalyst source material ferrocene to obtain aligned arrays of MWCNTs. The synthesized CNTs have been characterized by scanning electron microscopy (SEM), x-ray diffraction (XRD), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and Raman spectroscopy. In this technique, the need for the tedious and time-consuming preparation of metal catalysts and continuously fed carbon source material containing carrier gas can be avoided. This method is a single-step process where not many parameters are required to be monitored in order to prepare aligned MWCNTs. For the production of CNTs, the technique has great advantages such as low cost and easy operation.

RNA triphosphatase and guanylyl transferase activities are associated with the RNA polymerase protein L of rinderpest virus

Rinderpest virus (RPV) large (L) protein is an integral part of the ribonucleoprotein (RNP) complex of the virus that is responsible for transcription and replication of the genome. Previously, we have shown that recombinant L protein coexpressed along with P protein (as the L-P complex) catalyses the synthesis of all viral mRNAs in vitro and the abundance of mRNAs follows a gradient of polarity, similar to the occurrence in vivo. In the present work, we demonstrate that the viral mRNAs synthesized in vitro by the recombinant L or purified RNP are capped and methylated at the N-7 guanine position. RNP from the purified virions, as well as recombinant L protein, shows RNA triphosphatase (RTPase) and guanylyl transferase (GT) activities. L protein present in the RNP complex catalyses the removal of gamma-phosphate from triphosphate-ended 25 nt RNA generated in vitro representing the viral N-terminal mRNA 5' sequence. The L protein forms a covalent enzyme-guanylate intermediate with the GMP moiety of GTP, whose formation is inhibited by the addition of pyrophosphate; thus, it exhibits characteristics of cellular GTs. The covalent bond between the enzyme and nucleotide is acid labile and alkali stable, indicating the presence of phosphoamide linkage. The C-terminal region (aa 1717-2183) of RPV L protein alone exhibits the first step of GT activity needed to form a covalent complex with GMP, though it lacks the ability to transfer GMP to substrate RNA. Here, we describe the biochemical characterization of the newly found RTPase/GT activity of L protein.

Structural Insights into the acyl-intermediates of plasmodium falciparum fatty acid synthesis pathway; the mechanism of expansion of acyl carrier protein core

Acyl carrier protein (ACP) plays a central role in fatty acid biosynthesis. However, the molecular machinery that mediates its function is not yet fully understood. Therefore, structural studies were carried out on the acyl-ACP intermediates of Plasmodium falciparum using NMR as a spectroscopic probe. Chemical shift perturbation studies put forth a new picture of the interaction of ACP molecule with the acyl chain, namely, the hydrophobic core can protect up to 12 carbon units, and additional carbons protrude out from the top of the hydrophobic cavity. The latter hypothesis stems from chemical shift changes observed in C-alpha and C-beta of Ser-37 in tetradecanoyl-ACP. C-13, N-15-Double-filtered nuclear Overhauser effect (NOE) spectroscopy experiments further substantiate the concept; in octanoyl (C-8)- and dodecanoyl (C-12)-ACP, a long range NOE is observed within the phosphopantetheine arm, suggesting an arch-like conformation. This NOE is nearly invisible in tetradecanoyl (C-14)-ACP, indicating a change in conformation of the prosthetic group. Furthermore, the present study provides insights into the molecular mechanism of ACP expansion, as revealed from a unique side chain-to-backbone hydrogen bond between two fairly conserved residues, Ile-55 HN and Glu-48 O. The backbone amide of Ile-55 HN reports a pK(a) value for the carboxylate, similar to 1.9 pH units higher than model compound value, suggesting strong electrostatic repulsion between helix II and helix III. Charge-charge repulsion between the helices in combination with thrust from inside due to acyl chain would energetically favor the separation of the two helices. Helix III has fewer structural restraints and, hence, undergoes major conformational change without altering the overall-fold of P. falciparum ACP.

Two-Step Folding of Donor-Acceptor Foldamers

In a series of polymers containing alternately placed electron-rich dialkoxyilaphthalene (DAN) donors and electron-deficient pyromellitic diimide (PDI) acceptors linked by hexa(oxyethylene) (OE-6) segments, the ability to form a folded D-A stack was intentionally disrupted by random inclusion of varying amounts of a comonomer that is devoid of DAN donor units. NMR spectroscopic studies of folding in these copolymers, induced by NH4SCN that coordinates with the OE-6 segments and facilitates the charge-transfer (C-T) induced D-A stacking, clearly reveals the presence of PDI units that are isolated and those that are located at the ends of (D-A),, stacks. Similar conclusions regarding the presence of stacked and unstacked regions along the polymer chain were also inferred from UV-vis spectroscopic studies that probe the evolution of charge-transfer band. One fascinating aspect of these copolymers wits their ability to undergo it two-step folding: first, short (D-A),, stacks are formed by the interaction of the NH4+ ion with some specific regions of the polymer chain, and subsequently these Stacks are further stacked via a two-point interaction with it suitably designed external folding agent that carries a DAN unit and all ammonium group. In the second step, the interaction first occurs by the coordination of the ammonium group of the folding agent with the OE-6 segment, which in turn facilitates the C-T interaction of the DAN unit with the adjacent uncomplexed PDI units along the polymer chain, leading to an increase ill the slacking. Variations of several spectral features, during both UV-vis and NMR spectroscopic titrations, clearly reveal this novel two-step folding process.

Epigallocatechin gallate is a slow-tight binding inhibitor of enoyl-ACP reductase from Plasmodium falciparum

Epigallocatechin gallate (EGCG) is known to have numerous pharmacological properties. In the present study, we have shown that EGCG inhibits enoyl–acyl carrier protein reductase of Plasmodium falciparum (PfENR) by following a two-step, slow, tight-binding inhibition mechanism. The association/isomerization rate constant (k5) of the reversible and loose PfENR–EGCG binary complex to a tight [PfENR–EGCG]* or EI* complex was calculated to be 4.0 × 10−2 s−1. The low dissociation rate constant (k6) of the [PfENR–EGCG]* complex confirms the tight-binding nature of EGCG. EGCG inhibited PfENR with the overall inhibition constant (Ki*) of 7.0 ± 0.8 nM. Further, we also studied the effect of triclosan on the inhibitory activity of EGCG. Triclosan lowered the k6 of the EI* complex by 100 times, lowering the overall Ki* of EGCG to 97.5 ± 12.5 pM. The results support EGCG as a promising candidate for the development of tea catechin based antimalarial drugs.

Generalized survival in step fluctuations

The properties of the generalized survival probability, that is, the probability of not crossing an arbitrary location R during relaxation, have been investigated experimentally (via scanning tunneling microscope observations) and numerically. The results confirm that the generalized survival probability decays exponentially with a time constant tau(s)(R). The distance dependence of the time constant is shown to be tau(s)(R)=tau(s0)exp[-R/w(T)], where w(2)(T) is the material-dependent mean-squared width of the step fluctuations. The result reveals the dependence on the physical parameters of the system inherent in the prior prediction of the time constant scaling with R/L-alpha, with L the system size and alpha the roughness exponent. The survival behavior is also analyzed using a contrasting concept, the generalized inside survival S-in(t,R), which involves fluctuations to an arbitrary location R further from the average. Numerical simulations of the inside survival probability also show an exponential time dependence, and the extracted time constant empirically shows (R/w)(lambda) behavior, with lambda varying over 0.6 to 0.8 as the sampling conditions are changed. The experimental data show similar behavior, and can be well fit with lambda=1.0 for T=300 K, and 0.5