Design,synthesis and biological evaluation of pyridyl substituted benzoxazepinones as potent and selective inhibitors of aldosterone synthase

Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC₅₀ <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC₅₀ of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC₅₀ = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development.     

Synchronizing Substrate Activation Rates in Multicomponent Reactions with Metal–Organic Framework Catalysts

A study on the influence of the cation coordination number, number of Lewis acid centers, concurrent existence of Lewis base sites, and structure topology on the catalytic activity of six new indium MOFs, has been carried out for multicomponent reactions (MCRs). The new indium polymeric frameworks, namely [In₈(OH)₆(popha)₆(H₂O)₄]?3 H₂O ( InPF‐16 ), [In(popha)(2,2′‐bipy)]?3 H₂O ( InPF‐17 ), [In₃(OH)₃(popha)₂(4,4′‐bipy)]?4 H₂O ( InPF‐18 ), [In₂(popha)₂(4,4′‐bipy)₂]?3 H₂O ( InPF‐19 ), [In(OH)(Hpopha)]?0.5 (1,7‐phen) ( InPF‐20 ), and [In(popha)(1,10‐phen)]?4 H₂O ( InPF‐21 ) (InPF=indium polymeric framework, H₃popha=5‐(4‐carboxy‐2‐nitrophenoxy)isophthalic acid, phen=phenanthroline, bipy=bipyridine), have been hydrothermally obtained by using both conventional heating (CH) and microwave (MW) procedures. These indium frameworks show efficient Lewis acid behavior for the solvent‐free cyanosilylation of carbonyl compounds, the one pot Passerini 3‐component (P‐3CR) and the Ugi 4‐component (U‐4CR) reactions. In addition, InPF‐17 was found to be a highly reactive, recyclable, and environmentally benign catalyst, which allows the efficient synthesis of α‐aminoacyl amides. The relationship between the Lewis base/acid active site and the catalytic performance is explained by the 2D seven‐coordinated indium framework of the catalyst InPF‐17 . This study is an attempt to highlight the main structural and synthetic factors that have to be taken into account when planning a new, effective MOF‐based heterogeneous catalyst for multicomponent reactions.     

A novel molecularly imprinted method with computational simulation for the affinity isolation and knockout of baicalein from Scutellaria baicalensis

A novel molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization with baicalein (BAI) as the template and used as solid‐phase extraction (SPE) adsorbent, aiming at the affinity isolation and selective knockout of BAI from Scutellaria baicalensis Georgi (SB). We used computational simulation to predict the optimal functional monomer, polymerization solvent and molar ratio of template to functional monomer. Characterization and performance tests revealed that MIP exhibited uniform spherical morphology, rapid binding kinetics, and higher adsorption capacity for BAI compared with nonimprinted polymer (NIP). The application of MIP in SPE coupled with high‐performance liquid chromatography to extract BAI from SB showed excellent recovery (94.3%) and purity (97.0%). Not only the single BAI compound, but also the BAI‐removed SB extract was obtained by one‐step process. This new method is useful for isolation and knockout of key bioactive compounds from herbal medicines. Copyright © 2015 John Wiley & Sons, Ltd.     

Ultra-lightweight cellulose foam material: preparation and properties

Ultra-lightweight cellulose foams were prepared by regeneration of sodium dodecyl sulfate (SDS)/cellulose/NaOH/urea blend solution via mechanical agitation and then freeze-drying. The morphology and properties of the blend solutions and foams were investigated via optical microscope, rheometer, BET and SEM. As a result, it was found that the inclusion complex structure between cellulose macromolecules and the solvent molecules was not destroyed. Moreover, the bubbles were about 20–50 μm in the solutions and larger (>100 μm) in the foams. Not only the micropores (bubbles) but also the nanopores could be observed in the wet and dried foams. The cellulose foams possessed ultra-low density of about 30 mg/cm³ and high specific surface area. The result of X-ray diffraction and Fourier transform infrared spectroscopy indicated that the cellulose foams were transited from cellulose I to cellulose II after dissolution and gelation. Bubbles inside the wet foams weakened the mechanical properties, but inversely increased the mechanical properties in the dried foams. Typical “J”-shaped curves were observed during the mechanical test, which revealed good compressive strength of dried foams. In this work, cellulose foams with ultra-lightweight and good mechanical properties were obtained, which exhibited great potentials for further development and comprehensive utilization of cellulose.     

Highly improved crystallization behavior of poly(L‐lactide) induced by a novel nucleating agent: substituted‐aryl phosphate salts

In this work, a novel nucleating agent (NA) based on substituted‐aryl phosphate salts was introduced into poly(L‐Lactide) (PLLA). The nonisothermal and isothermal crystallization behaviors of nucleated PLLA samples were investigated through differential scanning calorimetry (DSC), wide angle X‐ray diffraction, and polarized optical microscope (POM). Furthermore, the effect of annealing treatment on the cold crystallization behaviors of nucleated samples was also investigated. The results show that the crystallization of PLLA, whether for the melt crystallization (including nonisothermal and isothermal crystallization process) or for the cold crystallization (including the cold crystallization occurring during the DSC heating process and during the annealing process), is greatly dependent upon the content of NA. At relatively lower NA content (≤0.1 wt%), the nucleation effect of NA is inconspicuous, however, at higher NA content (≥0.2 wt%), it exhibits great nucleation effect for the crystallization of PLLA. Further results show that the double endothermic peak of PLLA depends on the temperature applied for the crystallization. Copyright © 2012 John Wiley & Sons, Ltd.     

Molecularly Imprinted Polypyrrole for DNA Determination

In this study graphite electrodes modified by a thin DNA‐imprinted polypyrrole layer, which was able to bind specific target‐DNA, are reported. For this aim, electrochemical synthesis of polypyrrole was performed on a pencil graphite electrode by cyclic voltammetry (CV) or by potential pulse sequences (PPS). The modified electrode surface was used for electrochemical determination of target‐DNA by differential pulse voltammetry. According to our best knowledge this is a first report on the application of DNA‐imprinted polymer for the determination of target‐DNA. The results showed that the molecularly imprinted polypyrrole (MIPPy) layer that formed on the carbon electrode surface was sensitive for target‐DNA, while the nonimprinted polypyrrole layer was not sensitive to the same target‐DNA. Comparison of electrodes modified using PPS and CV techniques is presented.     

Surface and Catalytic Properties of K/V Catalysts Coating on Porous Al2O3 Substrate

The morphology of different ratio K/V catalysts supported on porous α‐alumina substrate was investigated by atomic force microscopy (AFM). Changes in the particle size distribution, pore size distribution were analyzed respectively using AFM software. In addition, their catalytic activities and compositions for carbon oxidation were studied by x‐ray diffraction (XRD), differential scanning calorimetry (DSC), and temperature‐programmed reactions (TPR). As a result, with the increase of K concentration, the mean particle size gradually increased and the mean pore size decreased. According to the catalytic activity studies, the catalytic activity of the KVO₃ and K₃V₅O₁₄ phases are more effective than KCl.