N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

Capsule contraction after continuous curvilinear capsulorhexis

We report two cases of capsular bag contraction that occurred within 1 month after continuous curvilinear capsulorhexis, phacoemulsification, and intraocular lens implantation. Neither patient had a known risk for this complication. Both patients had a neodymium:YAG laser anterior capsulotomy, which disrupted the capsulorhexis margin and led to prompt capsular bag distension.     

Crosslinking kinetics of SBR composites containing vulcanized ground scraps as filler

The aim of this study was to characterize the cure reaction of styrene–butadiene rubber (SBR) composites containing industrial rubber scraps. Different proportions of SBR ground scraps (SBR-r), varying from 10 to 80 parts per hundred of rubber, were incorporated into a base formulation of identical composition. Crosslink formation and the kinetics of the cure reaction were evaluated through oscillatory disk rheometry, differential scanning calorimetry, and crosslink density. Cure characteristics, such as scorch time and cure time, decreased with increasing SBR-r content. Minimum torque indicated only a small variation in the viscosity with the incorporation of SBR-r. The maximum torque decreased with the addition of scrap rubber, as a consequence of the reduction in virgin rubber content where crosslinks had been formed. Crosslink density values corroborated these findings, presenting a slight decrease with the increase in the SBR-r content. The kinetic study indicated lower enthalpy values for SBR-r composites compared to those of the control sample. The kinetic parameters, such as activation energy and reaction order, indicated a change in the mechanism of reaction, related to the increased complexity of the systems.     

Characterization and corrosion protection properties of polypyrrole / montmorillonite electropolymerized onto aluminium alloy 1100

Films of Polypyrrole/Montmorillonite (PPy/MT) clays were electropolymerized potentiostatically on aluminium alloy 1100, using sodium dodecylbenzenesulfonate (SDBS) as a dopant. Two clay species were used: Na⁺-Montmorillonite (MT-Na) and modified-Montmorillonite (MT-M). The characterization of the PPy/MT films performed by XRD and TEM shows that the exfoliation method employed, as well the electrochemical polymerization method used in this work, allow nanocomposite materials to be obtained. The PPy/MT films were found to have less electrical conductivity than pure PPy. The corrosion protection of aluminium alloy 1100 covering PPy/MT was evaluated by electrochemical techniques in 0.05 mol L⁻¹ NaCl medium. The electrochemical parameters derived from the polarization curves, together with the EIS data, revealed that the corrosion resistance of PPy/clay coatings depends on the type and concentration of Montmorillonite employed. The best performance in the corrosion protection of the aluminum was achieved with PPy/MT films containing 1% of clay.     

NiMo/C Used as Magnetic Support for SILP Catalysts

In this work, supported ionic liquid (IL) phases catalysts were prepared based on Pd dispersed in IL phases supported on magnetic particles of nickel/molybdenum covered with carbon (NiMo/C). The magnetic support was prepared via CVD method at 800 °C. XRD analysis showed the phases of metallic nickel and molybdenum carbide. The presence of carbon in these materials was confirmed by TEM/EDS and thermogravimetric analysis (TG) analysis. Pd particles were dispersed in 1 and 2.5 wt% of the IL 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm·BF₄), which were immobilized on the support surface via impregnation method. TG analysis shows a weight loss between 300 and 420 °C attributed to the BMIm·BF₄, confirming the existence of IL on the support surface. The prepared materials were investigated in hydrogenations reactions of 1,5-cyclooctadiene and nitrobenzene, and the influence of IL on the activity and selectivity of these catalysts were observed. These materials have great potential for catalysis applications, because they bring together the advantages of the IL in the catalyst surface and the facility of magnetic materials separation.     

Modulation of Biodistribution,Pharmacokinetics, and Photosensitivity with the Delivery Vehicle of a Bacteriochlorin Photosensitizer for Photodynamic Therapy

Intravenous (i.v.) formulations with various amounts of organic solvents [PEG₄₀₀, propylene glycol (PG), cremophor EL (CrEL)] were used to deliver a fluorinated sulfonamide bacteriochlorin to mice, rats, and minipigs. Biodistribution studies in mice showed that a low‐content CrEL formulation combines high bioavailability with high tumor‐to‐muscle and tumor‐to‐skin ratios. This formulation was also the most successful in the photodynamic therapy of mice with subcutaneously implanted CT26 murine colon adenocarcinoma tumors. Pharmacokinetic studies in mice and minipigs revealed that with the same low CrEL formulation, the half‐life of the photosensitizer in the central compartment was longer in minipigs. Differences in biodistribution with the various formulations, and in pharmacokinetics between the two animal species with the same formulation, are attributed to the interaction of the formulations with low‐density lipoproteins (LDLs). Skin photosensitivity studies in rats showed that 30 min exposure of the skin to a solar simulator 7 days after i.v. administration of the fluorinated sulfonamide bacteriochlorin at 1 mg kg^?1 did not elicit significant skin reactions.     

Thermal aging of Pd/Pt/Rh automotive catalysts under a cycled oxidizing–reducing environment

Mono- and multi-metallic (bi- and tri-) Pt, Pd and Rh supported on cerium-promoted alumina (La Roche, SAS-1/16) catalysts were tested for activity as TWC, both fresh [G.C. Koltsakis, and A.M. Stamatelos, Progr. Energy Combust. Sci. 23 (1997) 1] and after accelerated aging. Aging consisted of a treatment at 900°C for 5 h during which an oxidizing (2.5% O₂, 10% H₂O, in N₂) and a reducing (5.0% CO, 10% H₂O, in N₂) feedstream were cycled at 0.017 Hz through the catalyst. Activity tests were carried out by increasing temperature from 100 to 600°C at 3°C min⁻¹, while two oxidizing and reducing (±0.5 A/F) feedstreams were alternately (1 Hz) fed through the reactor at 125 000 h⁻¹ (STP). Conversion was continuously analyzed. Light-off temperature, T₅₀, conversion at 500°C (normal running temperature), X₅₀₀, and the stoichiometric window (A/F from 14.13 to 15.13) for stationary feedstreams, were determined.