Characterization of Novel Aminobenzylcantharidinimides and Related Imides by Proton NMR Spectra and Their Effects on NO Induction

Various acidic anhydrides including cantharidin were converted into corresponding aminobenzylcantharidinimide 3a and analogous imides 3b～k (at the ortho, meta, and para positions) with 35%～87% yields by reacting with aminobenzylamines and triethylamine. The two methyl side chains of cantharidinimides 3ao , 3am , and 3ap, and related imides had more than two chiral centers; the lone pair of electrons of nitrogen displayed a different chemical shift and coupling constant in H‐NMR spectra when the amino group of benzylamine was in the ortho position. These cantharidinimides had parent aniline, pyridine, and naphthalene plane structures, and the primary amine nucleophilicity and basicity might reflect the inductive electron’s negative effect on chemical shifts. We prepared cantharidinimides by heating the reactants cantharidin 1a , aliphatic and aromatic acid anhydrides, primary benzylic amines, and aniline derivatives to ca. 200 °C with 3 mL of dry toluene, and 1～2 mL of triethylamine in high‐pressure sealed tubes (Buchi glasuster 0032) to produce cantharidinimides and their analogues in good yields. The para‐aminobenzylic imides showed greater inhibition of nitric oxide (NO) synthesis by NO synthase (NOS) than did ortho‐ and meta‐aminobenzylic imides. Compound 3fp , para‐aminobenzylic norbonane‐imide, had the most potent effect on inducible NOS among the tested compounds and showed 35% inhibition.     

Energy release rates in a constrained epoxy disc with Hookean and Mooney–Rivlin materials

Assuming that the disc material can be modeled either as Mooney–Rivlin or as Hookean and the steel ring enclosing the disc as Hookean, the energy release rates as a function of the crack length are evaluated and compared. Two loadings are considered––one in which the surface of the star shape hole in the disc is loaded by a uniform pressure and the other in which the temperature of the composite body is uniformly raised. It is found that the linear and the nonlinear analyses give qualitatively similar results for the two loadings. For each load, the energy release rate increases with an increase in the starter crack length, reaches a maximum value and then decreases gradually.     

Stress-concentration factors for semielliptical notches in beams under pure bending

Elliptical notches in rectangular beams under pure bending are examined photoelastically. Stress-concentration factors due to a single elliptical notch are obtained for wide ranges of 2a/h andd/h, where 2a, d, andh are the width of notch, depth of notch, and depth of beam, respectively. In particular, the geometries of the optimum elliptical notches producing the least stress concentrations are obtained. Almost the whole elliptical boundary of these notches are stressed to the same peak, which indicates that these notches will probably produce the least stress concentrations among all notches, elliptical or nonelliptical. The graphs herein will enable the designers to find the stress-concentration factors of elliptical notches and to pick out the geometry of the optimum notch which will give the least stress concentration for any given values of 2a/h andd/h. Stresses and the stress-concentration factors at the bottom of the beam opposite the notch are also obtained. These stresses, though smaller in magnitude, are of an opposite sign to the peak stress at the notch. For brittle materials, a smaller tensile stress may be more critical than a large compressive stress; therefore, these stress-concentration factors are also given.     

Localization and Screening Enhancement in Asymmetric Binary Ionic Mixtures

The equation of state of binary ionic mixtures of similar ions, such as nitrogen, oxygen and carbon, has been extensively studied. The study of dense asymmetric mixtures, where Z₂ >> Z₁, has primarily focused on mixtures of hydrogen and iron at solar conditions. Using molecular dynamics simulations, we examine the behavior of highly asymmetric binary ionic mixtures, where the coupling of the high‐Z species may be orders of magnitude higher than the coupling of the low‐Z species. For the conditions we have studied, we find that strong correlations and signatures of solidification occur in the high‐Z species, while the low‐Z species exists as a freely flowing fluid within the high‐Z solid matrix. Solidification of the low‐Z species is correlated with the coupling between the two components. Using the Widom expansion method, we compute the plasma screening enhancement of the nuclear reaction rates for Z = 1 in a high‐Z matrix. We also provide some estimates of the coefficient of binary diffusion in the mixture. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Design, synthesis and biological characterization of novel inhibitors of CD38

Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca(2+) messenger molecule, cyclic ADP-ribose, from NAD(+). It is well established that this novel Ca(2+) signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD(+) complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound 1-14). A number of these compounds exhibited moderate inhibition of the NAD(+) utilizing activity of CD38, with Compound 4 showing the highest potency. The crystal structure of CD38/Compound 4 complex and computer simulation of Compound 7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds 4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development.     

Detecting small lung tumors in mouse models by refractive-index microradiology

Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm(3) with accuracy better than 1 × 10(-3) mm(3). This level of performance is currently suitable for animal studies, while further developments are required for clinical application.     

A Short and Efficient Synthesis of a Novel Diarylheptanoid Isolated from Pleuranthodium Racemigerum

The first total synthesis of the linear diarylheptanoid 1‐(4″‐methoxyphenyl)‐7‐(4′‐hydroxyphenyl)‐(E)‐hept‐2‐ene, which has a uniquely nonconjugated olefin, was achieved. The synthetic route employed an olefin cross‐metathesis as a key step. Beginning with commercially available 3‐(4‐hydroxyphenyl)propan‐1‐ol, the final product was made in three steps with a 52% yield.     

Hammett correlations in the chemistry of 3-phenylpropyl radicals

The energetics and kinetics of the reaction of variously substituted benzyl radicals with a model alkene were calculated at the G3(MP2)-RAD//B3-LYP/6-31G(d) level of theory to determine whether such reactions are amenable to Hammett analysis. The reactions were studied both in the gas phase and in toluene solution in the temperature range 298-353 K; calculations include 1D-hindered rotor corrections for low frequency torsional modes, and the solvation energies were calculated using COSMO-RS at the BP/TZP level of theory. The addition reaction was found to be dominated by radical stabilization effects, but under circumstances where olefin substituent effects were decoupled from aryl substituent effects, a modest polar effect comes into play, which is enhanced by solvation. Reasonable correlations with empirical substituent parameters such as Hammett σ and σ(?) are observed for the enthalpy of activation, but additional entropic factors act to decrease the degree of correlation with respect to free energies and rate coefficients, confirming hypotheses from earlier experimental work. Substituent effects on the reverse β-fragmentation reaction, and potential cyclization of the 3-phenylpropyl radicals formed by addition are also discussed.     

Interaction of an edge dislocation with a coated elliptic inclusion

This paper presents an analytical solution for plane elasticity problems of an elliptically cylindrical layered media subject to an arbitrary edge dislocation. Based on the technique of conformal mapping and the method of analytical continuation in conjunction with the alternating technique, the general expressions of the displacements and stresses, where an edge dislocation is located in matrix, coating layer and inclusion are obtained. The numerical results of image forces exerted on a generalized edge dislocation are carried out by using the generalized Peach–Koehler equation. As a numerical illustration, both the image forces and equilibrium positions are presented for different material combinations and relative thickness of a coating layer. The result shows that the thickness and the shear modulus of the coating layer have a strong influence on the stability of dislocation.