Regioselective organocadmium alkylations of substituted quinones.

A series of substituted quinones was alkylated with diethylcadmium. Regiochemistry of addition shifted from quinol formation to conjugate addition as a function of the steric and electronic effects of the substituents.     

HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants

The acquisition of drug-resistant mutations by infectious pathogens remains a pressing health concern, and the development of strategies to combat this threat is a priority. Here we have applied a general strategy, inverse design using the substrate envelope, to develop inhibitors of HIV-1 protease. Structure-based computation was used to design inhibitors predicted to stay within a consensus substrate volume in the binding site. Two rounds of design, synthesis, experimental testing, and structural analysis were carried out, resulting in a total of 51 compounds. Improvements in design methodology led to a roughly 1000-fold affinity enhancement to a wild-type protease for the best binders, from a Ki of 30-50 nM in round one to below 100 pM in round two. Crystal structures of a subset of complexes revealed a binding mode similar to each design that respected the substrate envelope in nearly all cases. All four best binders from round one exhibited broad specificity against a clinically relevant panel of drug-resistant HIV-1 protease variants, losing no more than 6-13-fold affinity relative to wild type. Testing a subset of second-round compounds against the panel of resistant variants revealed three classes of inhibitors: robust binders (maximum affinity loss of 14-16-fold), moderate binders (35-80-fold), and susceptible binders (greater than 100-fold). Although for especially high-affinity inhibitors additional factors may also be important, overall, these results suggest that designing inhibitors using the substrate envelope may be a useful strategy in the development of therapeutics with low susceptibility to resistance.     

Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-beta-lactam

We report herein the synthesis and biological evaluation of bile acid dimers linked through 1,2,3-triazole and bis-beta-lactam. The dimers were synthesized using 1,3-dipolar cycloaddition reaction of diazido bis-beta-lactams , and terminal alkynes derived from cholic acid/deoxycholic acid in the presence of Cu(i) catalyst (click chemistry). These novel molecules were evaluated in vitro for their antifungal and antibacterial activity. Most of the compounds exhibited significant antifungal as well as antibacterial activity against all the tested fungal and bacterial strains. Moreover, their in vitro cytotoxicities towards HEK-293 and MCF-7 cells were also established.     

Synthesis,Enzyme Inhibition,and Molecular Docking Studies of Hydrazones from Dichlorophenylacetic Acids

A series of hydrazones 5a–i were synthesized by the condensation of hydrazides derived from dichlorophenylacetic acids with different aromatic aldehydes and ketones. Their structures were confirmed by spectroscopic data and elemental analysis. Hydrazones 5a–i were evaluated for α‐glucosidase and urease inhibition activities. Five compounds exhibited potent α‐glucosidase inhibitory potential with IC₅₀ values 8.5 ± 0.3, 22.2 ± 0.78, 32.9 ± 1.5, 34 ± 2.4, and 170.6 ± 7.5 μM, respectively, which are many times better than that of the standard inhibitor acarbose (IC₅₀ = 840 ± 1.73 μM). Furthermore, molecular docking study was performed to explore the binding mode in the active sites of α‐glucosidase and urease enzymes.     

铝掺杂ZnMnO纳米晶体的载流子调控铁磁性

通过溶胶-凝胶自燃烧技术合成了Zn_0.95-xAl_xMn_0.05O(x=0、0.03、0.05和0.07)稀磁半导体材料. 并且研究了Al掺杂对Zn_0.95-xAl_xMn_0.05O结构、电学和磁学性质的效果. X射线衍射显示合成的组合物为单相六方晶系纤锌矿型晶体结构,类似于氧化锌.显微图像显示颗粒呈团簇状,但一些单个颗粒呈现六角形纹理. 观察到的电阻率随温度升高(达450 oC)而降低,显示为半导体行为特征.所有组合物具有室温铁磁行为. 饱和磁化强度的值随着Al(载流子)浓度的增加而增加.     

Physical aspects of magnetized Jeffrey nanomaterial flow with irreversibility analysis

This research presents the applications of entropy generation phenomenon in incompressible flow of Jeffrey nanofluid in the presence of distinct thermal features. The novel aspects of various features, such as Joule heating, porous medium, dissipation features, and radiative mechanism are addressed. In order to improve thermal transportation systems based on nanomaterials, convective boundary conditions are introduced. The thermal viscoelastic nanofluid model is expressed in terms of differential equations. The problem is presented via nonlinear differential equations for which analytical expressions are obtained by using the homotopy analysis method (HAM). The accuracy of solution is ensured. The effective outcomes of all physical parameters associated with the flow model are carefully examined and underlined through various curves. The observations summarized from current analysis reveal that the presence of a permeability parameter offers resistance to the flow. A monotonic decrement in local Nusselt number is noted with Hartmann number and Prandtl number. Moreover, entropy generation and Bejan number increases with radiation parameter and fluid parameter.     

α-glucosidase inhibitors isolated from Mimosa pudica L.

The aim of the study was to isolate digestive enzymes inhibitors from Mimosa pudica through a bioassay-guided fractionation approach. Repeated silica gel and sephadex LH 20 column chromatographies of bioactive fractions afforded stigmasterol, quercetin and avicularin as digestive enzymes inhibitors whose IC₅₀ values as compared to acarbose (351.02 ± 1.46 μg mL^?1) were found to be as 91.08 ± 1.54, 75.16 ± 0.92 and 481.7 ± 0.703 μg mL^?1, respectively. In conclusion, M. pudica could be a good and safe source of digestive enzymes inhibitors for the management of diabetes in future.     

Coherent Control of the Hartman Effect through a Photonic Crystal with Four-Level Defect Layer

In this paper, we examine the transmission of a probe field through a one dimensional photonic crystal (1DPC) when the sixth layer of the crystal is doped with four level atoms. We analyze effects of the external driving field on the passage of weak probe field across the photonic crystal. It is found that for the phase time delay of the probe photons, intensity of the driving field switches the Hartman effect from sub to superluminal character. It is interesting to note that in our model, the superluminal transmission of the probe pulse is accompanied by a negligibly small absorption of the incident beam. It ensures that the probe field does not attenuate while passing through the photonic crystal. A similar switching of the Hartman effect may be obtained by adjusting detuning of the probe field related to the excited states of the four-level doping atoms.     

Time-slot interchange of 40 Gbits/s variable length optical packets using conversion-dispersion-based tunable delays

We demonstrate tunable time-slot interchange of 40 Gbits/s optical data packets using a conversion-dispersion-based tunable optical delay element. Odd and even data packets are extracted from an input signal, delayed relative to one another in a highly dispersive medium, and then multiplexed back together. Tunability is demonstrated by operating with two different packet lengths, 182 and 288 bits/packet, and a bit error rate of <10(-9) is achieved.     

The 1,4-diaza[2.2.2] Bicyclooctane—hydrogen peroxide complex as a source of anhydrous hydrogen peroxide: the preparation of bis(trialkylsilyl) peroxides

The hazard and inconvenience of storing and handling concentrated hydrogen peroxide can be avoided by using instead the solid $\text{1}\text{2}$ complex which 1,4-diazabicyclo[2.2.2] octane forms with hydrogen peroxide, it reacts with trialkylchlorosilanes to give bis(trialkylsilyl) peroxides in good yield.