Cross-docking study on InhA inhibitors: a combination of Autodock Vina and PM6-DH2 simulations to retrieve bio-active conformations

InhA, the NADH-dependent enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis (Mtb) is the proposed main target of the first-line antituberculosis drug isoniazid (INH). INH activity is dependent on activation by the catalase peroxidase KatG, a Mtb enzyme whose mutations are linked to clinical resistance to INH. Other inhibitors of InhA that do not require any preliminary activation are known. The design of such direct potent inhibitors represents a promising approach to circumvent this resistance mechanism. An ensemble-docking process with four known InhA X-ray crystal structures and employing the Autodock Vina software was performed. Five InhA inhibitors whose bioactive conformations are known were sequentially docked in the substrate cavity of each protein. The efficiency of the docking was assessed and validated by comparing the calculated conformations to the crystallographic structures. For a same inhibitor, the docking results differed from one InhA conformation to another; however, docking poses that matched correctly or were very close to the expected bioactive conformations could be identified. The expected conformations were not systematically well ranked by the Autodock Vina scoring function. A post-docking optimization was carried out on all the docked conformations with the AMMP force field implemented on the VEGAZZ software, followed by a single point calculation of the interaction energy, using the MOPAC PM6-DH2 semi-empirical quantum chemistry method. The conformations were subsequently submitted to a PM6-DH2 optimization in partially flexible cavities. The resulting interaction energies combined with the multiple receptor conformations approach allowed us to retrieve the bioactive conformation of each ligand.     

Proton-coupled intervalence charge transfer: concerted processes

The kinetics of proton-induced intervalence charge transfer (IVCT) may be measured electrochemically by generating one of the members of the IVCT couple in situ and following its conversion by means of the electrochemical signature of the other member of the couple. In the case of the diiron complex taken as an example, the reaction kinetics analysis, including the H/D isotope effect, clearly points to the prevalence of the concerted proton-intervalence charge transfer pathway over the stepwise pathways. A route is thus open toward systematic kinetic studies of proton-induced IVCT aiming at uncovering the main reactivity parameters and the factors that control the occurrence of concerted versus stepwise pathways.     

Picosecond measurements of the third order susceptibility tensor in liquids

Single frequency Jamin interferometry is used for observation of non-linear susceptibility tensor measurements in the picosecond range (25 ps). At low density, when avoiding the polarization state instabilities, the displacement of the fringes leads to the measurement of two components of the nonlinear susceptibility tensor. It is shown that X_xyyx (ω = ω + ω - ω) decreases when the pulse duration is reduced, whereas X_{xxxx (ω = ω + ω - ω)} remains constant. This is interpreted by the difference between the orientational and vibrational molecular contributions.     

In vivo NMR of hyperpolarized 3He in the human lung at very low magnetic fields

We present NMR measurements of the diffusion of hyperpolarized 3He in the human lung performed at fields much lower than those of conventional MRI scanners. The measurements were made on standing subjects using homebuilt apparatus operating at 3mT. O(2)-limited transverse relaxation (T(2) up to 15-35s) could be measured in vivo. Accurate global diffusion measurements have been performed in vivo and in a plastic bag; the average apparent diffusion coefficient (ADC) in vivo was 14.2+/-0.6mm(2)/s, whereas the diffusion coefficient in the bag (3He diluted in N(2)) was 79.5+/-1mm(2)/s. 1D ADC mapping with high SNR ( approximately 200-300) demonstrates the real possibility of performing quality lung imaging at extremely low fields.     

La polyveoline,nouvel indolosesquiterpene isole du polyalthiasuaveolens,annonacees

The structure and absolute configuration of polyveoline, new indolosesquiterpene from Polyalthiasuaveolena, Annonaceae, were determined by X-ray crystal lographic study.     

ESR of X-ray irradiated lithium boracites

ESR spectra of paramagnetic defects induced by X-ray irradiation in lithium chloroboracites and bromoboracites have been measured for the first time, at 9 GHz and room temperature. ESR parameters are deduced by computer simulations of the spectra for polycrystalline powders and a single crystal. The paramagnetic center is characterized by an isotropic g — factor and an anisotropic hyperfine interaction with a boron nucleus. It is shown to be an unpaired electron trapped in a vacant site of the network and localized on a sp³ boron orbital. The defect is similar to the boron electron center (BEC) detected in borate glasses.     

Etude structurale des sulfotellurures de terres rares (LS)2Te1 + x (L = Tb,Dy, Ho,Er, Tm et Y). II. Surstructure des phases ordonnées. Macles d'ordre

The (LS)₂Te_{1 + x} compounds have an orthorhombic subcell, with a layered structure and vacant Te sites, and a monoclinic superstructure (a = b = 6.658, c = 13.657 Å, γ = 102°43′ for (HoS)₂Te_1.34). The order-disorder transition occurs at about 450°C. In the superstructure Te planes between (L₄S) tetrahedra layers are ordered with $\text{B2}\text{m}$ symmetry; however, some sites remain partially vacant. The S atoms conserve mmm symmetry, but the metallic atoms are slightly displaced from their substructure position (R = 0.037). Ordering occurs so that each Te plane can be oriented in two different ways. Therefore, there are two kinds of domains, with respect to a twinning rule. These domains are observed by direct-imaging high-resolution electronic microscopy and are about 100 Å wide.     

Radical reactions of C84

Pulse radiolysis and steady-state radiolysis experiments describing the radical and electron transfer reactions of C₈₄ are reported here for the first time. C₈₄ reacts readily with radiolytically generated chloromethyl (^•CCl₃) and trichloromethylperoxyl (CCl₃OO^•) radicals in CCl₄. The formation of the radical adduct has been confirmed from its characteristic absorption in the UV (320 nm) and visible (480 nm). Radical-induced oxidation in 1,2-dichloroethane (1,2-DCE) resulted in a short lived transient absorbing at 920 nm. Reduction of C₈₄ in toluene/2-propanol/acetone could be conveniently followed by formation of an absorption band with an absorption maximum at 960 nm.