Nitroarenes as Antitubercular Agents: Stereoelectronic Modulation to Mitigate Mutagenicity

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro group in these compounds is activated through different mechanisms, both enzymatic and non‐enzymatic, in mycobacteria prior to binding to the target of interest. From a whole‐cell screening program, we identified a novel lead nitrobenzothiazole (BT) series that acts by inhibition of decaprenylphosphoryl‐β‐d ‐ribose 2′‐epimerase (DprE1) of Mycobacterium tuberculosis (Mtb). The lead was found to be mutagenic to start with. Our efforts to mitigate mutagenicity resulted in the identification of 6‐methyl‐7‐nitro‐5‐(trifluoromethyl)‐1,3‐benzothiazoles (cBTs), a novel class of antitubercular agents that are non‐mutagenic and exhibit an improved safety profile. The methyl group ortho to the nitro group decreases the electron affinity of the series, and is hence responsible for the non‐mutagenic nature of these compounds. Additionally, the co‐crystal structure of cBT in complex with Mtb DprE1 established the mode of binding. This investigation led to a new non‐mutagenic antitubercular agent and demonstrates that the mutagenic nature of nitroarenes can be solved by modulation of stereoelectronic properties.     

Bulk and interfacial physical properties of aqueous solutions of sodium lauryl sulphate: Part IV: Dilute aqueous solution behavior by electron spin resonance studies and by pH and surface tension measurements

The electron spin resonance spectrum of the nitroxide label 2,2,6,6 – TetraMethyl – 4 – Piperidone – Oxide (TEMPO) has been investigated in aqueous solutions of a purified and commercially available impure samples of sodium lauryl sulphate (NaLS) for a wide range of concentrations. The spectra were recorded at 24°C as a function of surfactant concentration. The reorientational correlation times T_θ of the TEMPO label in aqueous solutions were calculated using the Kivelson's theory. Using the T_θ data qualitative analysis has been carried out in an attempt to understand the microscopic effects produced by the hydrophobic part of the surfactant on the water structure and the hydrophobic-hydrophobic interactions in water. Four major discontinuities in the τ_θ results have been identified with the purified NaLS system. They are found to occur at NaLS concentrations of 0.008 wt.%, 0.015 wt.%, 0.23 and 1.73 wt.%. The latter two concentrations represent the first and the second critical micelle concentration (CMC) of the surfactant while the first two concentrations reveal the existence of premicellar association and dissociation processes, respectively. These discontinuities have been also confirmed by the pH data and by surface tension results from the du Noüy ring method. The effect of addition of lauryl alcohol and sodium chloride on τ_θ values was also studied. The additive action has been found to produce an additional discontinuity, corresponding to the mixture CMC, in the τ_θ versus concentration plot. Analysis of other effects such as solution aging and hydrolysis of NaLS are also included. The applicability of the spin labelling technique for the study of aqueous solution behavior of NaLS is discussed by comparing data reported in the literature.     

Kinetic study of the solid-state reaction between phthalic anhydride and P-nitroaniline

The addition reaction between the compacted powders of phthalic anhydride and p-nitroaniline was studied. Both the reactants of equal particle size, were mixed in 1-to-1 molar ratio and compacted. Three particle sizes — 0.0065 cm, 0.0178 cm and 0.0376 cm and three compaction pressures — 302.0 kgf/cm², 785.0 kgf/cm² and 1208.0 kgf/cm² were used for the study. Conversions were measured at 80°, 90°, 100°, 110° and 120°C for 1/2, 1, 2, 4, 8, 12, 16, 20 and 24 hours. The reaction rate changed to a constant value, after an initial phase boundary process. The mole percentage conversions increased with decrease in particle size, increase in compaction pressure corresponding to a decrease in the initial porosity of the compact. It was also observed that the final porosity of the compact increased with increase in reaction temperature. Combination of Jander's model and parabolic rate law was used to calculate the values of the reaction rate constant equivalent. The activation energy was calculated to be 14 to 34 kilocalories per gram mole.     

The microstructural and hardening behaviour of tricalcium silicate pastes in the presence of calcium chloride

A sequential examination of strength development in terms of microhardness was studied during paste hydration of C₃S in the presence of 2 and 5% CaCl₂ and at w/s ratios of 0.3 or 0.5. An attempt has been made to relate strength with microstructural features studied by means of Scanning Electron Microscopy. Generally, at earlier periods it was found that the 2% addition of CaCl₂ gave the strongest material; the effect was most pronounced in the 6-month sample of the series with 0.3 w/s. The high strength for the sample prepared at a w/s ratio of 0.3 may be related to a high CaO/SiO₂ C-S-H-phase, low porosity, and possibly a hydrated calcium hydroxy chloride complex. The pore size distribution was also measured. In general, the higher the porosity the lower the strengths but the relationship was not perfectly linear even on the semi-logarithmic plot.     

Significance of low water—solid ratio and temperature on the physico-mechanical characteristics of hydrates of tricalcium aluminate

Hydration characteristics are reported of tricalcium aluminate studied at 20 and 80 °C using water-solid ratios of 0.2 and 1.0. Hydration products were subjected to differential thermal analysis, thermogravimetric analysis, scanning electron microscopy, length change, porosity and pore size distribution, and micro-hardness measurements. Hydration proceeds faster at 80 °C than at 20 °C and the cubic C₃AH₆ phase is detected in the first few seconds. At 20 °C hydration occurs with the initial formation of the hexagonal phases and expansion is continuous. At higher temperatures and a water-solid ratio of 0.2, after an initial small expansion, the dimensional change is low. The product at 80 °C develops more than fourfold the hardness value developed at 20 °C. After 2 days of hydration, porosity, per cent C₃AH₆ and microhardness are 15.2%, 83% and 38.9 kg/mm²; corresponding values for the product obtained at 20 °C are 21.5%, 75% and 9.1 kg/mm². Microstructural examination of the material formed at 80 °C indicates a closely welded and continuous network of the cubic phase. These results reveal that at a low water-solid ratio and higher temperatures the formation of the cubic phase from C₃A results in an enhancement of strength.     

Influence of triethanolamine on the hydration characteristics of tricalcium silicate

The hydration characteristics of 3CaO.SiO₂ or β2CaO.SiO₂ are studied by an addition of 0.0, 0.1, 0.5 or 1.0% triethanolamine. The amount of Ca(OH)₂ found at 1, 3, 7 or 28 days was in the order C₃S + 0% TEA > C₃S +0.1% TEA > C₃S + 0.5% TEA > C₃S+1.0% TEA, irrespective of whether lime was estimated by X-ray, DTA, TGA or chemical analysis. The rate of hydration, in terms of the disappearance of 3CaO.SiO₂, showed that hydration proceeded faster in the presence of TEA after 1 day. Additions of TEA increase the induction period, promote the formation of a C-S-H with higher CaO/SiO₂ ratio, increase the formation of non-crystalline Ca(OH)₂ and enhance the surface area of the hydrated silicate product.     

Laminar film boiling on a porous vertical wall with uniform suction velocity

Laminar free convection film boiling on a porous vertical wall with uniform suction or blowing is analysed using boundary layer theory. The solutions are obtained assuming suction or blowing to be a disturbance superposed on the isothermal, impermeable wall case. Using a parameter involving the suction or blowing velocity, universal functions are derived for various values of Prandtl Number and c_p(T_w — T_sat)/h_fgPr. These universal functions can be used to estimate the heat transfer rate in the presence of suction or blowing. As expected, suction increases the heat transfer rate while blowing decreases the heat-transfer. Even small velocities of suction or blowing could significantly affect the heat transfer. It is also found that the effects of suction or blowing are more pronounced at lower wall superheats.     

Conductive electrospun PANi-PEO/TiO2 fibrous membrane for photo catalysis

The integration of electrospinning and electrospraying to prepare the fibrous catalytic filter membrane is demonstrated. The non-conductive polyethylene oxide (PEO) is blended with (±)-camphor-10-sulfonic acid (CSA) doped conductive polyaniline (PANi) for electrospinning. The conductive CSA/PANi-PEO composite fibers are produced upon electrospinning, which are used as the conductive collector for electrospraying process by which titanium dioxide (TiO₂) nanoparticles (NPs) are sprayed and allowed to adsorb on the fibers. The degree of adsorption and dispersion of nano TiO₂ catalysts on the surface of the CSA/PANi-PEO fibers exhibit a stronger dependence on weight percentage (wt%) of PANi in PEO solution and the strength of electrical conductivity of the fibers used during electrospraying. CSA/PANi-PEO fibers as collector reduce the wastage of TiO₂ NPs during electrospraying to lesser than 5%. Among the three different composition of PANi studied, PEO with 12 wt% PANi yields very uniform diameter and beads-free fibrous structure with higher electrical conductivity. 12 wt% CSA/PANi-PEO fibrous membrane is found to support for greater dispersion of TiO₂ NPs. The photocatalytic activity of the as-prepared TiO₂-PANi-PEO catalytic membrane is tested against the toxicant simulant 2-chloroethyl phenyl sulfide (CEPS) under the ultraviolet light irradiation. It is observed that the TiO₂ nanoparticles catalysts embedded PANi-PEO fibrous membrane decontaminated the toxicant CEPS significantly, which is due to uniform dispersion of the catalysts produced by the methodology.     

Pore Structure of Silica Gel

The effect of washing on the texture of silica gel has been investigated in terms of parameters such as porosity, pore size distribution, surface area and absorption of moisture. It was observed that if silica gel (before activation) is washed with water containing dissolved ions such as Ca and Mg wider pores are formed at the expense of smaller ones. This phenomenon has been explained in terms of change in the size distribution of gel particles which is brought about by solution of very fine particles followed by growth, through condensation, of larger particles. The experimental observations have been interpreted to suggest guidelines to control the texture of gels by washing with solutions comaining different cations.     

Molecular recognition of the Lewis Y antigen by monoclonal antibodies

The murine monoclonal antibody BR55-2 is directed against thetumor-associated antigen Lewis Y oligosaccharide. The LewisY core antigen is a difucosylated structure consisting of fourhexose units. Analysis of binding profiles of lactoseries isomericstructures by BR55–2 suggest that the binding epitopeincludes the OH-4 and OH-3 groups of the ß-D-galactoseunit, the 6-CH₃ groups of the two fucose units and the N-acetylgroup of the subterminal ß-D-N-acetylglucosamine (ßDGlcNAc).To elucidate the molecular recognition properties of BR55–2for the Y antigen, BR55–2 was cloned, sequenced and itsthree-dimensional structure was examined by molecular modeling.The crystal structure of BR96, another anti-Lewis Y antibody,solved in complex with a nonoate methyl ester Lewis Y tetrasaccharide,and the lectin IV protein in complex with a Lewis b tetrasaccharidecore were used as a guide to probe the molecular basis for BR55–2antigen recognition and specificity. Our modeling study showsthat BR55–2 shares similar recognition features for thedifucosylated type 2 lactoseries Lewis Y structure observedin the BR96-sugar complex. We observe that a major source ofspecificity for the Lewis Y structure by anti-Y antibodies emanatesfrom interaction with the ß-D-N-acetylglucosamineresidue and the nature of the structures extended at the reducingsite of the fucosylated lactosoamine.