Synthesis,Characterization, and In Vitro Antimicrobial Activity of Methyleneamine‐Linked Bis‐heterocycles

A new class of methyleneamine‐linked bis‐heterocycles that exhibit antimicrobial activity was synthesized. Bromination of 1 followed by condensation with thiourea gave 3 . The reaction of 3 with propargyl bromide in dry toluene under inert atmosphere led to the formation of 4 . Its subsequent reaction with different nitrile oxides using CuSO₄.5H₂O–sodiumascorbate system in a 2:1 mixture of water and tert‐butyl alcohol yielded the title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Preferential Reactivity of Pyridylmagnesiumchloride with N,N-Dialkyl Arylamides over Carbonitriles: Synthesis of 2-(Aroyl) Pyridines

Reaction of 2-pyridylmagnesium chlorides with N,N-dialkyl arylamides afford exclusively 2-(aroyl) pyridines in high yields and purity without the formation of any tertiary alcohol. This method employs easily available raw materials and avoids the use of hazardous lithium reagents and cryogenic conditions. Further, preferential reactivity of this Grignard reagent with N,N-dialkyl arylamides over its carbonitrile counterparts offers a variety of 2-(aroyl) pyridines including the ones containing carbonitrile groups on the aryl ring.     

Thermoluminescence studies of UV-irradiated Y2O3:Eu3+ doped phosphor

The present paper reports thermoluminescence (TL) glow curves of Eu³⁺-doped Y₂O₃ phosphor with different ultraviolet (UV) exposure times. The glow peak shows second-order kinetics of Eu³⁺-doped Y₂O₃, and corresponding kinetic parameters were evaluated using the peak shape method. Calculations of trap depth were carried out using different methods. The kinetics order, activation energy, and frequency factor were calculated. The recorded glow curve shifts towards higher intensity with longer UV exposure. The heating rate used for recording TL was 3.0 °C s^?1. Particle size and structure were verified by X-ray diffraction (XRD) pattern and morphology by scanning electron microscopy (SEM) imaging.     

Catalyst-free one-pot synthesis of benzimidazoles from 1,2-diaminoarenes and alcohols

A new and efficient protocol is described for the one-pot synthesis of benzimidazoles from a variety of aryl alcohols and 1,2-diaminoarenes. The yields were ranging from moderate to excellent. Moreover, the present method is utilizing alcohols instead of aldehydes and the reactions are carried out under solvent- and catalyst-free conditions, offering an environmentally benign process.     

Self‐Assembly of DNA–Oligo(p‐phenylene‐ethynylene) Hybrid Amphiphiles into Surface‐Engineered Vesicles with Enhanced Emission

Surface‐addressable nanostructures of linearly π‐conjugated molecules play a crucial role in the emerging field of nanoelectronics. Herein, by using DNA as the hydrophilic segment, we demonstrate a solid‐phase “click” chemistry approach for the synthesis of a series of DNA–chromophore hybrid amphiphiles and report their reversible self‐assembly into surface‐engineered vesicles with enhanced emission. DNA‐directed surface addressability of the vesicles was demonstrated through the integration of gold nanoparticles onto the surface of the vesicles by sequence‐specific DNA hybridization. This system could be converted to a supramolecular light‐harvesting antenna by integrating suitable FRET acceptors onto the surface of the nanostructures. The general nature of the synthesis, surface addressability, and biocompatibility of the resulting nanostructures offer great promises for nanoelectronics, energy, and biomedical applications.     

Design and Activity of Novel Oxadiazole Based Compounds That Target Poly(ADP-ribose) Polymerase

Novel PARP inhibitors with selective mode-of-action have been approved for clinical use. Herein, oxadiazole based ligands that are predicted to target PARP-1 have been synthesized and screened for the loss of cell viability in mammary carcinoma cells, wherein seven compounds were observed to possess significant IC₅₀ values in the range of 1.4 to 25 µM. Furthermore, compound 5u, inhibited the viability of MCF-7 cells with an IC₅₀ value of 1.4µM, when compared to Olaparib (IC₅₀ = 3.2 µM). Compound 5s also decreased cell viability in MCF-7 and MDA-MB-231 cells with IC₅₀ values of 15.3 and 19.2 µM, respectively. Treatment of MCF-7 cells with compounds 5u and 5s produced PARP cleavage, H2AX phosphorylation and CASPASE-3 activation comparable to that observed with Olaparib. Compounds 5u and 5s also decreased foci-formation and 3D Matrigel growth of MCF-7 cells equivalent to or greater than that observed with Olaparib. Finally, in silico analysis demonstrated binding of compound 5s towardsthe catalytic site of PARP-1, indicating that these novel oxadiazoles synthesized herein may serve as exemplars for the development of new therapeutics in cancer.     

Sensitivity enhancement and matrix effect evaluation during summation of multiple transition pairs—case studies of clopidogrel and ramiprilat

Sensitivity enhancement via summation of multiple MRM transition pairs is gaining popularity in tandem mass spectrometric assays. Numerous validation experiments describing the assays for two model substrates, clopidogrel and ramiprilat, were performed. The quantitation of clopidogrel was achieved by the summation of transition pairs m/z 322.2 to m/z 212.0 and m/z 322.2 to m/z 184.0, while that of ramiprilat was achieved by the summation of transition pairs m/z 389.2 to m/z 206.1 and m/z 389.2 to m/z156.1. The use of summation approach achieved sensitivities of >2 fold for both compounds as compared with the reported single MRM transition pair assays. The validation experiments addressed some important assay development issues, such as: (a) lack of impact of matrix effect; (b) unequivocal verification of the percentage contribution of each MRM transition pair towards sensitivity; (c) sensitivity enhancement factor achieved by summation approach of MRM transition pairs; and (d) accurate prediction of quality control samples using summation approach vs a single MRM transition pair. In summary, the appropriateness of using two MRM transition pairs for quantitation was demonstrated for both clopidogrel and ramiprilat. Additionally, pharmacokinetic application of the MRM transition pair assays using a summation approach was established for the two compounds. Copyright © 2009 John Wiley & Sons, Ltd.     

Modeling of three-dimensional pressure fields in sonochemical reactors with an inhomogeneous density distribution of cavitation bubbles. Comparison of theoretical and experimental results

During the last 50 years extensive experimental investigation has been carried out on the chemical effects of ultrasound, but limited work has been reported on modeling. This paper presents a new model in which a numerical calculation of the three-dimensional linear sound pressure field distribution in a commonly used sonoreactor containing three transducers is carried out. In this model the inhomogeneous three-dimensional time-dependent wave equation was solved using the finite difference approach. The modeled results are then compared with the experimentally measured values, and the agreement, in general, is found to be good. Further, our modeling studies have an advantage, since they clearly describe the continuous sound pressure field structure, unlike previously reported results in which some information is missing due to limited intermittent measured points.     

Mean spherical model for the square-well potential

The mean spherical model (MSM) equation has been solved for the aquare-well potential. Comparison of the MSM results with the simulation results shows the MSM radial distribution function and energy to be satisfactory in the liquid states.     

Correlation of ultrasonic scatterer size estimates for the statistical analysis and optimization of angular compounding

Ultrasonic scatterer size estimates generally have large variances due to the inherent noise of spectral estimates used to calculate size. Compounding partially correlated size estimates associated with the same tissue, but produced with data acquired from different angles of incidence, is an effective way to reduce the variance without making dramatic sacrifices in spatial resolution. This work derives theoretical approximations for the correlation between these size estimates, and the coherence between their associated spectral estimates, as functions of ultrasonic system parameters. A Gaussian spatial autocorrelation function is assumed to adequately model scatterer shape. Both approximations compare favorably with simulation results, which consider validation near the focus. Utilization of the correlation/coherence expressions for statistical analysis and optimization is discussed. Approximations, such as the invariance of phase and amplitude terms with angle, are made to obtain closed-form solutions to the derived spectral coherence near the focus and permit analytical optimization analysis. Results indicate that recommended parameter adjustments for performance improvement generally depend upon whether, for the system under consideration, the primary source of change in total coherence with rotation is phase term variation due to the change in the relative position of scattering sites, or field amplitude term variation due to beam movement.