Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety

As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.     

High-speed phase imaging by parallel phase-shifting digital holography

Parallel phase-shifting digital holography can obtain three-dimensional information of a dynamically moving object with high accuracy by using space-division multiplexing of multiple holograms required for phase-shifting interferometry. We demonstrated high-speed parallel phase-shifting digital holography and obtained images of the phase variation of air caused by a compressed gas flow sprayed from a nozzle. In particular, we found the interesting phenomenon of periodic phase distributions. Reconstructed images were obtained at frame rates of 20,000 and 180,000 frames per second.     

Nanocrystals Assembled by the Chemical Reaction of the Dispersion Solvent

The development of methods to pattern nanocrystals with different sizes and shapes remains a challenge. In this study, we demonstrate a unique class of bottom‐up approaches to assemble nanocrystals into patterns. Our approach for patterning nanocrystals focuses on the utilization and control of the chemical reaction of solvents surrounding nanocrystals. The photopolymerization of solvent molecules through a photomask creates time‐dependent concentration gradients of the solvents. Dispersed nanocrystals such as silver nanowires (AgNWs) migrate and are gradually organized and integrated into the polymerizing films based on the concentration gradients. The AgNW‐embedded film properties are determined by the organized AgNW structures and include light transmission and electrical conductivity. Overall, the demonstrated method is very simple, widely applicable to various nanocrystals and solvents, and can thus contribute to the development of a new class of nanocrystal patterning methods.     

Intramolecular C−H Amination of N-Alkylsulfamides by tert-Butyl Hypoiodite or N-Iodosuccinimide

1,3-Diamines are an important class of compounds that are broadly found in natural products and are also widely used as building blocks in organic synthesis. Although the intramolecular C−H amination of N-alkylsulfamide derivatives is a reliable method for the construction of 1,3-diamine structures, the majority of these methods involve the use of a transition-metal catalyst. We herein report on a new transition-metal-free method using tert-butyl hypoiodite (t-BuOI) or N-iodosuccinimide (NIS), enabling secondary non-benzylic and tertiary C−H amination reactions to proceed. The cyclic sulfamide products can be easily transformed into 1,3-diamines. Mechanistic investigations revealed that amination reactions using t-BuOI or NIS each proceed via different pathways.     

Multidimensional angle sensing method using guided-mode resonance

Optical Review - A waveguide grating on a transparent substrate can serve as an optical notch filter owing to guided-mode resonance. The filtering wavelength is highly sensitive to an incidence...     

The renormalization of the string operator in QCD

We shall observe that the renormalization of the string operator U(x₁, x₂; C) = Pexp{ig∫_x1^x2dx_μA^μ(x)} with an open path C (smooth and non-intersecting) is path-independently performed in any order of perturbation. To demonstrate this, the renormalization constants will be calculated up to order g⁴. Next the renormalization effect on the algebraic identity $\text{U(x}{}_1\text{, x}{}_2\text{;}\text{C}\text{)U(x}{}_2\text{, x}{}_3\text{;}\text{C}\text{) = U(x}{}_1\text{, x}{}_3\text{;}\text{C}\text{∪}\text{C}\text{)}$ will be discussed and it will be proved that the renormalization preserves the algebraic identity in any order of perturbation if the paths C and $\text{C}$ are smoothly connected at x₂. Finally, the string operator renormalization is extended to the case when the path C is smoothly closed (the Wilson loop operator). It is then shown that the renormalization factor which multiplicatively renormalizes the string operator in the case of the open path, is cancelled in any order of perturbation by the divergence appearing in the coincidence of the end points. As a results, the Wilson loop operator can be renormalized by the coupling constant renormalization alone.     

Isomeric metamorphosis: Si3E (E = S, Se, and Te) bicyclo[1.1.0]butane and cyclobutene

Group 14 and 16 hybrid heavy bicyclo[1.1.0]butanes (tBu2MeSi)4Si3E (E = S, Se, and Te) 2a-c have been prepared by the [1 + 2] cycloaddition reaction of trisilirene 1 and the corresponding chalcogen. Bicyclo[1.1.0]butanes 2 have exceedingly short bridging Si-Si bonds (2.2616(19) A for 2b and 2.2771(13) A for 2c), a phenomenon explained by the important contribution of the trisilirene-chalcogen pi-complex character to the overall bonding of 2. Photolysis of 2a and 2b produced their valence isomers, the heavy cyclobutenes 3a and 3b, featuring flat four-membered Si3E rings and a planar geometry of the Si=Si double bond. The mechanism of such isomerization was studied using deuterium-labeled 2a-d6 to ascertain the preference of the pathway, involving the direct concerted symmetry-allowed transformation of bicyclo[1.1.0]butane 2 to cyclobutene 3.     

Sonoluminescence of Na atom from NaCl solutions doped with ethanol

Sonoluminescence spectra from argon-saturated NaCl solution were measured in the concentration range of 0.5-4 M at the frequency of 138 kHz. The line broadening of sodium atom emission was observed at various acoustic powers in the range from 1.8 to 16.2 W. The sodium D line showed a maximum intensity at a NaCl concentration of 2 M, which corresponded to the maximum production of OH radicals estimated by KI dosimetry. The effects of the addition of a small amount of ethanol on the line width and intensity were closely investigated at various acoustic powers. The sodium line width increases with ethanol concentration and also with power, whereas the line intensity is strongly quenched with increasing ethanol concentration. The results conclusively show that the sodium emission occurs in the gas phase within bubbles. The line broadening is due to interactions with high-pressure argon, and the maximum relative density of gas at bubble collapse was estimated to be 59.5 from the comparison with spectroscopic data. Further line broadening and quenching upon the addition of ethanol arise from collisions with gaseous products obtained from the decomposition of ethanol. The mechanism of sodium excitation is inferred to be as follows. Sodium ions enter bubbles as droplets, and salts are formed because of the high temperature within bubbles. Sodium atoms are generated by the dissociation of salts and then undergo electronic excitation by OH and H radicals.