Deepika Singh

Cross-dehydrogenative coupling of azoles with α-C(sp3)-H of ethers and thioethers under metal-free conditions: functionalization of H-N azoles via C-H activation.

A metal-free cross-dehydrogenative coupling method for the synthesis of N-substituted azoles has been developed. The TBAI/TBHP system catalyzed the coupling of azoles with ethers and thioethers via α-C(sp(3))-H activation. Under the optimized conditions, a diverse range of un/substituted azoles such as 1H-benzimidazole, 9H-purine, 1H-benzotriazole, 1H-1,2,3-triazole, 1H-1,2,4-triazole, and 1H-pyrazole were successfully employed for coupling with various ethers and thioethers such as tetrahydrofuran, tetrahydropyran, 1,4-dioxane, diethyl ether, tetrahydrothiophene, and 1,3-dithiolane.

Cu–Mn Spinel Oxide Catalyzed Regioselective Halogenation of Phenols and N-Heteroarenes

A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N-halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para-selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation.

Synthesis, characterization and mechanistic-insight into the anti-proliferative potential of PLGA-gemcitabine conjugate.

Gemcitabine, a nucleoside analogue, is used in the treatment of various solid tumors, however, its efficacy is limited by rapid metabolism by cytidine deaminase and fast kidney excretion. In this study, a polymeric conjugate of gemcitabine was prepared by covalent coupling with poly(lactic-co-glycolic) acid (PLGA), in order to improve anticancer efficacy of the drug. The prepared conjugate was characterized by various analytical techniques including FTIR, NMR and mass spectroscopic analysis. The stability study indicated that the polymeric conjugate was more stable in plasma as compared to native gemcitabine. Further, in vitro cytotoxicity determined in a panel of cell lines including pancreatic cancer (MIAPaCa-2), breast cancer (MCF-7) and colon cancer (HCT-116), indicated that the cytotoxic activity of gemcitabine was retained following conjugation with polymeric carrier. In the nucleoside transportation inhibition assay, it was found that the prepared conjugate was not dependent on nucleoside transporter for entering into the cells and this, in turn, reflecting potential implication of this conjugate in the therapy of transporter- deficient resistance cancer. Further, the cell cycle analysis showed that the sub-G1 (G0) apoptotic population was 46.6% and 60.6% for gemcitabine and PLGA gemcitabine conjugate, respectively. The conjugate produced remarkable decrease in mitochondrial membrane potential, a marker of apoptosis. In addition, there was a marked increase in PARP cleavage and P-H2AX expression with PLGA gemcitabine conjugate as compared to native gemcitabine indicating improved apoptotic activity. The findings demonstrated the potential of PLGA gemcitabine conjugate to improve clinical outcome of gemcitabine based chemotherapy of cancer.

Numerical Study of the Effects of Reverse Sweep on Scramjet Inlet Performance

A comparative numerical study of performance parameters of a similar and an opposite sweep sidewall compression inlet is made. The focus of the study is the investigation of the impact of alternate backward-forward sweep on the compression sidewalls as opposed to back-ward sweep on all the sidewalls. Two equivalent scramjet inlet configurations are designed for this purpose. These inlets have the same wetted areas of compression and expansion and same height and width; but in one inlet all the compression surface are swept back (similar sweep inlet) whereas in the other inlet, alternate surfaces are swept backward and forward (opposite sweep inlet). The cowl closure in both cases begins at the start of the throat region. A three-dimensional Navier-Stokes code is used to calculate the flow through these inlets. Results of these calculations are used to compare the two designs for their performance and flow quality. Effects of boundary- layer ingestion on the performance and overall flow features are also investigated.

CAN-DO, CFD-based Aerodynamic Nozzle Design and Optimization program for supersonic/hypersonic wind tunnels

A design program is developed which incorporates a modern approach to the design of supersonic/hypersonic wind-tunnel nozzles. The approach is obtained by the coupling of computational fluid dynamics (CFD) with design optimization. The program can be used to design a 2D or axisymmetric, supersonic or hypersonic, wind-tunnel nozzles that can be modeled with a calorically perfect gas. The nozzle design is obtained by solving a nonlinear least-squares optimization problem (LSOP). The LSOP is solved using an iterative procedure which requires intermediate flowfield solutions. The nozzle flowfield is simulated by solving the Navier-Stokes equations for the subsonic and transonic flow regions and the parabolized Navier-Stokes equations for the supersonic flow regions. The advantages of this method are that the design is based on the solution of the viscous equations eliminating the need to make separate corrections to a design contour, and the flexibility of applying the procedure to different types of nozzle design problems.

Enantioselective Synthesis of N-PMP-1,2-dihydropyridines via Formal [4 + 2] Cycloaddition between Aqueous Glutaraldehyde and Imines.

A simple and highly practical one-pot formal [4 + 2] cycloaddition approach for the enantioselective synthesis of N-PMP-1,2-dihydropyridines (DHPs) is described. This chemistry involves an amino-catalytic direct Mannich reaction/cyclization followed by IBX-mediated chemo- and regioselective oxidation sequence between readily available aqueous glutaraldehyde and imines under very mild conditions. A series of N-PMP-1,2-DHPs have been prepared in high yields and excellent enantioselectivity. This method also gives access to both enantiomers of 1,2-DHPs in surplus amount by shifting the catalyst configuration.

Least-squares/parabolized Navier-Stokes procedure for optimizing hypersonic wind-tunnel nozzles

A new procedure is demonstrated for optimizing hypersonic wind-tunnel nozzle contours. The procedure couples a computational fluid dynamics (CFD) computer code to an optimization algorithm, and is applied to both conical and contoured hypersonic nozzles for the purpose of determining an optimal set of parameters to describe the surface geometry. A design objective function is specified based on the deviation from the desired test section flowfield conditions. The objective function is minimized by optimizing the parameters used to describe the nozzle contour based on the solution to a nonlinear least-squares problem. The effect of the changes in the nozzle wall parameters are evaluated by computing the nozzle flow using the parabolized Navier-Stokes equations. The advantage of the new procedure is that it directly takes into account the displacement effect of the boundary layer on the wall contour. The new procedure provides a method for optimizing hypersonic nozzles of high Mach numbers that have been designed by classical procedure, but are shown to produce poor flow quality due to the large boundary layers present in the test section. The procedure is demonstrated by finding the optimum design parameters for a Mach 10 conical nozzle and a Mach 6 and Mach 15 contoured nozzle.

Numerical simulation of shock-induced combustion/detonation in a premixed H2-air mixture using Navier-Stokes equations

A numerical study was conducted to address the structural stability of the oblique detonation wave. An attempt was made to isolate the structural instability predicted by Buckmasters (1990) linear stability analysis. For this study a detailed viscous flowfield with finite-rate chemistry was computed past a 20-deg wedge. The finite-rate chemistry was modeled by using a seven-species and seven-reaction model. Instability modes were isolated by analyzing the Fourier power spectrum of the H2O mass fraction at selected sample stations. No unstable temporal modes with dominant frequency were isolated. It was concluded that the instability which is predicted by the Buckmaster work was a high-frequency low-amplitude phenomenon. For engineering purposes, the oblique detonation wave is a stable phenomenon as long as sufficient levels of overdrive are present.

Numerical study of the performance of swept, curved compression surface scramjet inlets

A computational performance enhancement study was performed employing systematic modifications to a planarsidewall compression scramjet inlet operating at an entrance Mach number of 4 and at a dynamic pressure of 2040 psf. The variations included modifying the planar-side wall compression angle as a function of height, utilizing sidewall curvature, and employing, simultaneously, both forward-swept and reverse-swept compression surfaces. Turbulent flowfield solutions were generated by solving the Reynolds-averaged Navier-Stokes equations to obtain inlet performance parameters such as total-pressure recovery, mass capture, and flowfield pressure distortion (the ratio of maximum static pressure to minimum static pressure generated at the inlet exit plane). Additionally, an inviscid parametric study was performed by employing solutions to the Euler equations to optimize a cubic polynomial that defined the longitudinal sidewall geometry. A final viscous flowfield solution of the optimized inviscid inlet geometry yielded inlet performance improvements; however, inlet top-wall surface boundary-layer shock wave separation interactions persisted. Hence, this numerical study demonstrated that enhanced performance is obtainable via curved-wall geometric modifications to the standard planar-sidewall inlet design, although future work should employ constraints to mitigate detrimental flow separation effects.

Direct catalytic synthesis of densely substituted 3-formylpyrroles from imines and 1,4-ketoaldehydes

A sustainable method for the direct access to highly substituted 3-formylpyrroles from 1,4-ketoaldehydes and imine via formal [3 + 2] cycloaddition is reported. This reaction involves a one-pot amine catalyzed chemoselective Mannich-cyclization-aerobic oxidation sequence with good to high yields. Further application of the gram scale reaction as well as synthesis of fully substituted 3-formylpyrrole is also shown.