Mycobacterium leprae RecA is structurally analogous but functionally distinct from Mycobacterium tuberculosis RecA protein

Mycobacterium leprae is closely related to Mycobacterium tuberculosis, yet causes a very different illness. Detailed genomic comparison between these two species of mycobacteria reveals that the decaying M. leprae genome contains less than half of the M. tuberculosis functional genes. The reduction of genome size and accumulation of pseudogenes in the M. leprae genome is thought to result from multiple recombination events between related repetitive sequences, which provided the impetus to investigate the recombination-like activities of RecA protein. In this study, we have cloned, over-expressed and purified M. leprae RecA and compared its activities with that of M. tuberculosis RecA. Both proteins, despite being 91% identical at the amino acid level, exhibit strikingly different binding profiles for single-stranded DNA with varying GC contents, in the ability to catalyze the formation of D-loops and to promote DNA strand exchange. The kinetics and the extent of single-stranded DNA-dependent ATPase and coprotease activities were nearly equivalent between these two recombinases. However, the degree of inhibition exerted by a range of ATP:ADP ratios was greater on strand exchange promoted by M. leprae RecA compared to its M. tuberculosis counterpart. Taken together, our results provide insights into the mechanistic aspects of homologous recombination and coprotease activity promoted by M. lepare RecA, and further suggests that it differs from the M. tuberculosis counterpart. These results are consistent with an emerging concept of DNA-sequence influenced structural differences in RecA nucleoprotein filaments and how these differences reflect on the multiple activities associated with RecA protein. (C) 2011 Elsevier B.V. All rights reserved.

Fabrication of corrosion resistant, bioactive and antibacterial silver substituted hydroxyapatite/titania composite coating on Cp Ti

The present work is aimed at developing a bioactive, corrosion resistant and anti bacterial nanostructured silver substituted hydroxyapatite/titania (AgHA/TiO(2)) composite coating in a single step on commercially pure titanium (Cp Ti) by plasma electrolytic processing (PEP) technique. For this purpose 2.5 wt% silver substituted hydroxyapatite (AgHA) nanoparticles were prepared by microwave processing technique and were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM) methods. The as-synthesized AgHA particles with particle length ranging from 60 to 70 nm and width ranging from 15 to 20 nm were used for the subsequent development of coating on Cp Ti. The PEP treated Cp Ti showed both titania and AgHA in its coating and exhibited an improved corrosion resistance in 7.4 pH simulated body fluid (SBF) and 4.5 pH osteoclast bioresorbable conditions compared to untreated Cp Ti. The in vitro bioactivity test conducted under Kokubo SBF conditions indicated an enhanced apatite forming ability of PEP treated Cp Ti surface compared to that of the untreated Cp Ti. The Kirby-Bauer disc diffusion method or antibiotic sensitivity test conducted with the test organisms of Escherichia coli (E. coli) for 24 h showed a significant zone of inhibition for PEP treated Cp Ti compared to untreated Cp Ti. (C) 2011 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

Structures of new crystal forms of Mycobacterium tuberculosis peptidyl-tRNA hydrolase and functionally important plasticity of the molecule

The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase from M.similar to tuberculosis reported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure.

(Dimethylamino)borylene and Related Complexes of Electron-Rich Metal Fragments: Generation of Nucleophile-Resistant Cations by Spontaneous Halide Ejection

Spontaneous halide ejection from a three-coordinate Lewis acid has been shown to offer a remarkable new route to cationic metal complexes featuring a linear, multiply bonded boron-donor Ligand. The exploitation of electron-rich [CpM(PR3)(2)] fragments within boryl systems of the type LnMB(hal)NR2 leads to the spontaneous formation in polar solvents of chemically robust borylene complexes, [LnM(BNR2)](+), with exceptionally low electrophilicity and short M-B bonds. This is reflected by M-B distances (ca. 1.80 angstrom for FeB systems) which are more akin to alkyl-/aryl-substituted borylene complexes and, perhaps most strikingly, by the very low exothermicity associated with the binding of pyridine to the two-coordinate boron center (Delta H = -7.4 kcal mol(-1), cf. -40.7 kcal mol(-1) for BCl3). Despite the strong pi electron release from the metal fragment implied by this suppressed reactivity and by such short M-B bonds, the barrier to rotation about the Fe=B bond in the unsymmetrical variant [CpFe(dmpe)(BN{C6H4OMe-4}Me)](+) is found to be very small (ca. 2.9 kcal mol(-1)). This apparent contradiction is rationalized by the orthogonal orientations of the HOMO and HOMO-2 orbitals of the [CpML2](+) fragment, which mean that the M-B pi interaction does not fall to zero even in the highest energy conformation.

Evaluation of the role of disordered organic fluorine in crystal packing: insights from halogen substituted benzanilides

The determination of the crystal and molecular structures of a large number of compounds containing the C(sp(2))-F bond has been investigated in detail in halogenated benzanilides and also in liquids, namely the fluorinated amines. It has been observed that when the fluorine atom is present in the ortho or meta position with respect to the amide functionality in benzanilides or the amino group in fluorinated amines which are liquids at room temperature, the fluorine atom exhibits positional disorder. This is associated with changes in patterns of intermolecular interactions which affect crystal packing. Furthermore, the presence of a fluorine atom on the benzanilide framework, in the presence of a heavier halogen (chloro, bromo and iodo), meta or ortho to the amide group does not eliminate the disorder associated with these molecules. In this article, we highlight the salient features present in halogenated compounds exhibiting disorder in the position of organic fluorine with concomitant changes in crystal packing. This feature is also compared with related compounds exhibiting similarity in electronic features, namely positional disorder.

Dynamic Internal Cavities of Dendrimers as Constrained Media. A Study of Photochemical Isomerizations of Stilbene and Azobenzene Using Poly(alkyl aryl ether) Dendrimers

Dendritic rnicroenvironments defined by dynamic internal cavities of a dendrimer were probed through geometric isomerization of stilbene and azobenzene. A third-generation poly(alkyl aryl ether) dendrimer with hydrophilic exterior and hydrophobic interior was used as a reaction cavity in aqueous medium. The dynamic inner cavity sizes were varied by utilizing alkyl linkers that connect the branch junctures from ethyl to n-pentyl moiety (C(2)G(3)-C(5)G(3)). Dendrimers constituted with n-pentyl linker were found to afford higher solubilities of stilbene and azobenzene. Direct irradiation of trans-stilbene showed that C(5)G(3) and C(4)G(3) dendrimers afforded considerable phenanthrene formation, in addition to cis-stilbene, whereas C(3)G(3) and C(2)G(3) gave only cis-stilbene. An electron-transfer sensitized trans-cis isomerization, using cresyl violet perchlorate as the sensitizer, also led to similar results. Thermal isomerization of cis-azobenzene to trans-azobenzene within dendritic microenvironments revealed that the activation energy of the cis- to trans-isomer was increasing in the series C(5)G(3) < C(4)G(3) < C(3)G(3)

Structural, dielectric relaxation and piezoelectric characterization of Sr2+ substituted modified PMS-PZT ceramic

Pyrochlore phase free [Pb0.94Sr0.06] [(Mn1/3Sb2/3)(0.05)(Zr0.53Ti0.47)(0.95)] O-3 ceramics has been synthesized with pure Perovskite phase by semi-wet route using the columbite precursor method. The field dependences of the dielectric response and the conductivity have been measured in a frequency range from 50 Hz to 1 MHz and in a temperature range from 303 K to 773 K. An analysis of the real and imaginary parts of the dielectric permittivity with frequency has been performed, assuming a distribution of relaxation times. The scaling behavior of the dielectric loss spectra suggests that the distribution of the relaxation times is temperature independent. The SEM photographs of the sintered specimens present the homogenous structures and well-grown grains with a sharp grain boundary. The material exhibits tetragonal structure. When measured at frequency (100 Hz), the polarization shows a strong field dependence. Different piezoelectric figures of merit (k(p), d(33) and Q(m)) of the material have also been measured obtaining their values as 0.53, 271 pC/N and 1115, respectively, which are even higher than those of pure PZT with morphotropic phase boundary (MPB) composition. Thus the present ceramics have the optimal overall performance and are promising candidates for the various high power piezoelectric applications. (C) 2011 Elsevier B.V. All rights reserved.

Novel and efficient protocol for the syntheses of N-1 substituted thiohydantoin and a bicyclothiohydantoin under solvent-free conditions

A novel approach for the synthesis of N-1 substituted thiohydantoin has been developed to give quantitative yields of the desired products. The efficient synthesis of bis-thiohydantoin derivative and bicyclothiohydantoin has extended scope and applicability of present method. Solvent-free conditions and very easy work-up procedure make the reaction convenient and eco-friendly. All the products were characterized by spectroscopic techniques and elemental analysis, and finally the structure of representative ;compound was also confirmed by X-ray crystallography. (C) 2012 Elsevier Ltd. All rights reserved.

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

This paper deals with the synthesis of 2-deoxy-2-C-alkyl/aryl septanosides. A range of such septanoside derivatives was synthesized by using a common bromo-oxepine intermediate, involving C-C bond forming organometallic reactions. Unsaturated, seven-membered septanoside vinyl bromides or bromo-oxepines, obtained through a ring expansion methodology of the cyclopropane derivatives of oxyglycals, displayed a good reactivity towards several acceptor moieties in C-C bond forming Heck, Suzuki and Sonogashira coupling reactions, thus affording 2-deoxy-2-C-alkyl/aryl septanosides. Whereas Heck and Sonogashira coupling reactions afforded 2-deoxy-2-C-alkenyl and -alkynyl derivatives, respectively, the Suzuki reaction afforded 2-deoxy-2-C-aryl septanosides. Deprotection and reduction of the 2-deoxy-2-alkenyl derivative afforded the corresponding 2-deoxy-2-C-alkyl septanoside free of protecting groups. The present study illustrates the reactivity of bromo-oxepine in the synthesis of hitherto unknown septanosides, branching out at C-2, through C-C bond formation with alkyl and aryl substituents.

Synthesis and an Evaluation of Molecular Conformation and Crystal Packing in Two Substituted 4-Phenylquinolines

The title compounds, namely Methyl 2-methyl-4 -phenylquinoline-3-carboxylate (I), C18H15NO2, and (2E)-3-(3,4-dimethoxyphenyl)-1-(2-methyl-4 -phenylquinolin-3-yl)prop-2-en-1-one (II), C27H23NO3, comprising of the phenyl ring, exhibit differences in conformational behaviour with respect to the plane of the quinoline fragment. (I) contains the methyl ester moiety whereas (II) contains the chalcone fragment, consisting of a double bond and phenyl group containing dimethoxy groups as substituents. The dihedral angles between the phenyl group and the quinoline ring is 82.77 (7)A degrees in (I), and 79.02 (8)A degrees in (II) respectively. It is the weak C-H center dot center dot center dot O=C H-bond and C-H center dot center dot center dot pi interactions which dictate packing of molecules in (I). In (II), it is C-H center dot center dot center dot N and C-H center dot center dot center dot pi, involving the dimethoxy ring, which controls packing of molecules in the crystal lattice. In addition, pi center dot center dot center dot pi aromatic stacking interactions involving the quinoline fragment is present in all the molecules. The title compounds, namely methyl-2-methyl-4 -phenylquinoline-3-carboxylate (I), C18H15NO2, and (2E)-3-(3,4-dimethoxyphenyl)-1-(2-methyl-4 -phenylquinolin-3-yl)prop-2-en-1-one (II), C27H23NO3, comprising of the phenyl ring, exhibit differences in conformational behaviour with respect to the plane of the quinoline fragment. (I) contains the methyl ester moiety whereas (III) contains the chalcone fragment, consisting of a double bond and phenyl group containing dimethoxy groups as substituents. The dihedral angles between the phenyl group and the quinoline ring is 82.77 (7)A degrees in (I), and 79.02 (8)A degrees in (II) respectively. It is the weak C-H center dot center dot center dot O=C H-bond and C-H center dot center dot center dot pi interactions which dictate packing of molecules in (I). In (II), it is C-H center dot center dot center dot N and C-H center dot center dot center dot pi, involving the dimethoxy ring, which controls packing of molecules in the crystal lattice. In addition, pi center dot center dot center dot pi aromatic stacking interactions involving the quinoline fragment is present in all the molecules.

Functionally graded hydroxyapatite-alumina-zirconia biocomposite: Synergy of toughness and biocompatibility

Functionally Gradient Materials (FGM) are considered as a novel concept to implement graded functionality that otherwise cannot be achieved by conventional homogeneous materials. For biomedical applications, an ideal combination of bioactivity on the material surface as well as good physical property (strength/toughness/hardness) of the bulk is required in a designed FGM structure. In this perspective, the present work aims at providing a smooth gradation of functionality (enhanced toughening of the bulk, and retained biocompatibility of the surface) in a spark plasma processed hydroxyapatite-alumina-zirconia (HAp-Al2O3-YSZ) FGM bio-composite. In the current work HAp (fracture toughness similar to 1.5 MPa.m(1/2)) and YSZ (fracture toughness similar to 62 MPa.m(1/2)) are coupled with a transition layer of Al2O3 allowing minimum gradient of mechanical properties (especially the fracture toughness similar to 3.5 MPa.m(1/2)).The in vitro cyto-compatibilty of HAp-Al2O3-YSZ FGM was evaluated using L929 fibroblast cells and Saos-2 Osteoblast cells for their adhesion and growth. From analysis of the cell viability data, it is evident that FGM supports good cell proliferation after 2, 3, 4 days culture. The measured variation in hardness, fracture toughness and cellular adhesion across the cross section confirmed the smooth transition achieved for the FGM (HAp-Al2O3-YSZ) nanocomposite, i.e. enhanced bulk toughness combined with unrestricted surface bioactivity. Therefore, such designed biomaterials can serve as potential bone implants. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis of benzofuran based 1,3,5-substituted pyrazole derivatives: As a new class of potent antioxidants and antimicrobials-A novel accost to amend biocompatibility

In search for a new antioxidant and antimicrobial agent with improved potency, we synthesized a series of benzofuran based 1,3,5-substituted pyrazole analogues (5a-l) in five step reaction. Initially, o-alkyl derivative of salicyaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, on treatment with 1,8-diaza bicyclo5.4.0]undec-7-ene (DBU) in the presence of molecular sieves. Further, aldol condensation with vanillin, Claisen-Schmidt condensation reaction with hydrazine hydrate followed by coupling of substituted anilines afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR, mass, elemental analysis and further screened for their antioxidant and antimicrobial activities. Among the tested compounds 5d and 5f exhibited good antioxidant property with 50% inhibitory concentration higher than that of reference while compounds 5h and 5l exhibited good antimicrobial activity at concentration 1.0 and 0.5 mg/mL compared with standard, streptomycin and fluconazole respectively. (C) 2012 Elsevier Ltd. All rights reserved.