Het(aryl)isatin to het(aryl)aminoindoline scaffold hopping: A route to selective inhibitors of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC₅₀ of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design.     

突出矿井瓦斯抽放限制影响因素的AHP-熵权法评价模型

为提高煤与瓦斯突出矿井瓦斯抽放效果,建立了3个一级指标、14个二级指标的突出矿井瓦斯抽放限制影响因素评价指标体系,利用AHP和熵权法分别确定指标因子主、客观权重.通过实地调研分析和反馈验证了AHP-熵权法的可行性和正确性,利用加权平均法确定评价模型的综合权重.研究表明:封孔方式、钻孔半径、抽放时间、煤体裂隙发育程度和抽放负压是目前影响煤矿瓦斯抽放效果的主控因素.     

Molecular design of ambipolar redox-active molecules II: closed-shell systems

This mini-review highlights key structural features that should be taken into account when creating ambipolar redox-active closed-shell metal-free molecules. This type of compound is strongly required for the fabrication of all-organic ‘poleless’ batteries and semiconductors. The suggested strategies aimed at stabilization of both oxidized (cationic) and reduced (anionic) redox-states are based on the comprehensive analysis of the most successful structures taken from the recent publications.     

Response surface methodology toward the optimization of high-energy carotenoid extraction from Aristeus antennatus shrimp

High-energy assisted extraction techniques, like ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), are widely applied over the last years for the recovery of bioactive compounds such as carotenoids, antioxidants and phenols from foods, animals and herbal natural sources. Especially for the case of xanthophylls, the main carotenoid group of crustaceans, they can be extracted in a rapid and quantitative way with the use of UAE and MAE.     

Pure tetrahedral quadruple systems with index two

An oriented tetrahedron defined on four vertices is a set of four cyclic triples with the property that any ordered pair of vertices is contained in exactly one of the cyclic triples. A tetrahedral quadruple system of order $n$ with index $\lambda$, denoted by ${\text{TQS}}_{\lambda }\left(n\right)$, is a pair $\left(X,\mathrm{?}\right)$, where $X$ is an $n$‐set and $\mathrm{?}$ is a set of oriented tetrahedra (blocks) such that every cyclic triple on $X$ is contained in exactly $\lambda$ members of $\mathrm{?}$. A ${\text{TQS}}_{\lambda }\left(n\right)$ is pure if there do not exist two blocks with the same vertex set. When $\lambda =1$, the spectrum of a pure TQS $\left(n\right)$ has been completely determined by Ji. In this paper, we show that there exists a pure ${\text{TQS}}_2\left(n\right)$ if and only if $n\equiv 1,2\left(\mathrm{mod}3\right)$ and $n\ge 7$. A corollary is that a simple ${\text{QS}}_4\left(n\right)$ also exists if and only if $n\equiv 1,2\left(\mathrm{mod}3\right)$ and $n\ge 7$.     

An inequality connecting entropy distance,Fisher Information and large deviations

In this paper we introduce a new generalisation of the relative Fisher Information for Markov jump processes on a finite or countable state space, and prove an inequality which connects this object with the relative entropy and a large deviation rate functional. In addition to possessing various favourable properties, we show that this generalised Fisher Information converges to the classical Fisher Information in an appropriate limit. We then use this generalised Fisher Information and the aforementioned inequality to qualitatively study coarse-graining problems for jump processes on discrete spaces.     

D3h‐Symmetric Porphyrin‐Based Rigid Macrocyclic Ligands for Multicofacial Multinuclear Complexes in a One‐Nanometer‐Sized Cavity

The one‐step synthesis of D_3h‐symmetric cyclic porphyrin trimers 1 composed of three 2,2′‐[4,4′‐bis(methoxycarbonyl)]bipyridyl moieties and three porphyrinatozinc moieties was achieved from a nickel‐mediated reductive coupling of meso‐5,15‐bis(6‐chloro‐4‐methoxycarbonylpyrid‐2‐yl)porphyrinatozinc. Although cyclic trimers 1 were obtained as a mixture that included other cyclic and acyclic porphyrin oligomers, an extremely specific separation was observed only for cyclic trimers 1 when using columns of silica gel modified with pyrenylethyl, cyanopropyl, and other groups. Structural analysis of cyclic trimers 1 was carried out by means of NMR spectroscopy and X‐ray crystallography. Treatment of an η³‐allylpalladium complex with a cyclic trimer gave a tris(palladium) complex containing three η³‐allylpalladium groups inside the space, which indicated that the bipyridyl moieties inside the ring could work as bidentate metalloligands.     

Bis-tridentate IrIII Phosphors Bearing Two Fused Five-Six-Membered Metallacycles: A Strategy to Improved Photostability of Blue Emitters

Iridium complexes bearing chelating cyclometalates are popular choices as dopant emitters in the fabrication of organic light-emitting diodes (OLEDs). In this contribution, we report a series of blue-emitting, bis-tridentate Ir^III complexes bearing chelates with two fused five-six-membered metallacycles, which are in sharp contrast to the traditional designs of tridentate chelates that form the alternative, fused five-five metallacycles. Five Ir^III complexes, Px-21 – 23 , Cz-4 , and Cz-5 , have been synthesized that contain a coordinated dicarbene pincer chelate incorporating a methylene spacer and a dianionic chromophoric chelate possessing either a phenoxy or carbazolyl appendage to tune the coordination arrangement. All these tridentate chelates afford peripheral ligand–metal–ligand bite angles of 166–170°, which are larger than the typical bite angle of 153–155° observed for their five-five-coordinated tridentate counterparts, thereby leading to reduced geometrical distortion in the octahedral frameworks. Photophysical measurements and TD-DFT studies verified the inherent transition characteristics that give rise to high emission efficiency, and photodegradation experiments confirmed the improved stability in comparison with the benchmark fac-[Ir(ppy)₃] in degassed toluene at room temperature. Phosphorescent OLED devices were also fabricated, among which the carbazolyl-functionalized emitter Cz-5 exhibited the best performance among all the studied bis-tridentate phosphors, showing a maximum external quantum efficiency (EQE_max) of 18.7 % and CIE_x,y coordinates of (0.145, 0.218), with a slightly reduced EQE of 13.7 % at 100 cd m⁻² due to efficiency roll-off.     

QEPAS系统中石英音叉模态仿真计算与研究

对石英音叉增强型光声光谱(QEPAS)系统中常用的石英音叉进行了有限元模态计算，获得石英音叉前6阶振型与模态频率，认知了第4阶对称摆动振型为有效振动，利用单因素法分析了石英音叉的音臂长度l₁、音臂宽度w₁、音臂厚度t、音臂切角θ、音臂圆孔直径d及音臂圆孔高度h对低阶有效共振频率(Fre)的影响，敏感度依次为： l₁> w₁>d>θ>t>h，考虑实际设计情形，筛选出了l₁，w₁，d与h四个石英音叉设计变量，采用Box-Behnken实验设计方案与RSM(response surface methodology)方法，以Fre为函数目标，建立l₁，w₁，d与h的二次回归响应面模型，得到了参数之间的交互作用，利用Design-Expert软件对响应面模型进行设计参数反求，结果表明，在15 000 Hz≤Fre≤25 000 Hz计算区域内误差较小，基本满足QEPAS系统的计算需求，所提出的研究与设计方法具有一定通用性，可为QEPAS系统中石英音叉结构参数设计提供参考。