水环境介质中有机污染物微观分布的理论模型——污染物·水复合体·水簇模型

以水簇模拟水环境介质, 水体中有机污染物的分子状态用水-有机污染物分子复合体模拟,得出有机污染物在水环境介质中微观分布的数学表达式, 经过微观动力学方法处理, 得到了相应的数学解析式.用 ab initio 方法 STO-3G 基组计算了4个多环芳烃在水中的微观分布情况, 计算结果与辛醇-水分配系数的实验值相吻合.     

Directed evolution of cyclic peptides for inhibition of autophagy

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Unfortunately, chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of the autophagosome maturation machinery—with mid-nanomolar affinities and disrupted protein–protein interactions (PPIs) between LC3 and its binding partners in vitro. The most promising LC3-binding SUPR peptide accessed the cytosol at low micromolar concentrations as measured by chloroalkane penetration assay (CAPA) and inhibited starvation-mediated GFP-LC3 puncta formation in a concentration-dependent manner. LC3-binding SUPR peptides re-sensitized platinum-resistant ovarian cancer cells to cisplatin treatment and triggered accumulation of the adapter protein p62 suggesting decreased autophagic flux through successful disruption of LC3 PPIs in cell culture. In mouse models of metastatic ovarian cancer, treatment with LC3-binding SUPR peptides and carboplatin resulted in almost complete inhibition of tumor growth after four weeks of treatment. These results indicate that SUPR peptide mRNA display can be used to develop cell-penetrating macrocyclic peptides that target and disrupt the autophagic machinery in vitro and in vivo.

SUPR peptide mRNA display was used to evolve a cell-permeable, macrocyclic peptide for autophagy inhibition.     

Di­methyl 2‐(4‐bromo­phenyl)‐10,11‐di­methoxy‐2,3,7,8‐tetra­hydro­spiro­[azepino[2,1‐a]­iso­quinoline‐3,9′‐fluorene]‐4,5‐di­carboxyl­ate

The title compound, C₃₈H₃₂BrNO₆, is a new photochromic tetra­hydro­azepinoiso­quinoline (THAI). The longest spiro bond [1.589 (4) Å] can be broken very easily by UV light, leading to ring opening. This explains the photochromic behaviour.     

Coupling Reaction of 4-Chloro-7-H-Pyrrolo[2,3-d]Pyrimidine with 2,3,5-Tri-O-Acetyl-β-D-Ribofuranosyl Chloride

Tubercidin (4-amino-7--D-riobofuranosyl-7-H-pyrrolo[2,3-d]pyrimidine) 1, an antibio-tic substance produced in the culture broth of Streptomyces tubericidus1, is an adenosine analog in which N-7 is replaced by a carbon atom. It has attracted much attention due to the biological activities for the growth inhibition of certain tumors, and many derivatives of tubercidin have been synthesized2-5.For the synthesis of tubercidin analogs, 4-chloro-7-H-pyrrolo[2,3-d]pyrimidine-2,3,5-tri-O-acetyl--D-r…     

Discovery of a Novel 5-HT_(2A) Inhibitor by Pharmacophore-based Virtual Screening

The serotonin 2A(5-HT2A) receptor has been implicated in several neurological conditions and potent 5-HT2A antagonists have therapeutic effects in the treatment of schizo phrenia and depression.In this study,a potent novel 5-HT2A inhibitor 05245768 with a Ki value of (593.89±34.10) nmol/L was discovered by integrating a set of computational approaches and experiments(protein structure prediction,pharmacophore-based virtual screening,automated molecular docking and pharmacological bioassay).The 5-HT2A recept...     

Crystal structure and the role of cation group factor in the third‐order nonlinear optical properties of cadmium complexes constructed by 1,3‐dithiole‐2‐thione‐4,5‐dithiolato ligand

A cadmium complex bis(benzyltriethylammonium) bis(1,3‐dithiole‐2‐thione‐4,5‐dithiolato)‐cadmium(II) ((TEBA)₂[Cd(DMIT)₂]) has been synthesized and its crystal structure has been determined by means of X‐ray single‐crystal diffraction. The central cadmium(II) ion coordinates with two DMIT, which constructed a distorted tetrahedron environment. Its third‐order nonlinear optical properties have been studied using Z‐scan technique with 20 ps pulses at wavelength 1064 nm. Its third‐order nonlinear susceptibility χ⁽³⁾ value was determined to be 1.24 × 10⁻¹⁹ m² V⁻², the figure of merit, χ⁽³⁾/α₀, was estimated to be 2.64 × 10⁻²⁰ m³ V⁻². Copyright © 2011 John Wiley & Sons, Ltd.     

全概率公式及其应用技巧

对全概率公式的内涵进行剖析、引申与扩展,构造性地运用全概率公式计算一些复杂事件的概率,通过实例探讨其应用技巧.     

桂枝的引药作用机制及其对环丙沙星在小鼠体内分布的影响

研究了桂枝和桂皮醛对环丙沙星在小鼠体内分布的影响,并基于此探讨了桂枝作为引药使用的作用机制.实验中将小鼠分为三组,分别灌胃生理盐水、桂枝(50gkg-1)和桂皮醛(0.25mLkg-1),然后对三组小鼠尾静脉注射环丙沙星(20mgkg-1),并以荧光法测定不同时间点小鼠体内各组织中环丙沙星的浓度.结果显示桂枝、桂皮醛均促进了环丙沙星在四肢的分布,桂枝与桂皮醛组相对于生理盐水组可将环丙沙星在四肢的含量提高约40%~200%,证实了桂枝引药到达肢节的作用.桂枝与桂皮醛组对环丙沙星分布情况的影响没有显著性差异,说明桂皮醛很可能是发挥桂枝引药作用的主要物质.     

(R)-乙基-2-吡啶亚砜与(4R,5R)-TADDOL包结晶体 [C7H9NOS·C31H30O4]的晶体结构分析

（Ｒ）－乙基－２－吡啶亚砜与（４Ｒ，５Ｒ）－二（羟基－二苯基－甲基）－２，２－二甲基－１，３－二氧戊环（ＴＡＤ－ＤＯＬ）可以形成物质的量比为１∶１的手性包结晶体，Ｘ射线衍射分析确定该晶体属单钭晶系，Ｐ２１空间群，ａ＝０．９７０１（２）ｎｍ，ｂ＝０．９９５３（２）ｎｍ，ｃ＝１．７３９２（２）ｎｍ；β＝９２．０７９°（１４），Ｖ＝１．６７８１（５）ｎｍ３，Ｚ＝２，Ｄｃ＝１．２３０ｇ／ｃｍ３，分子式Ｃ３８Ｈ３９ＮＯ５Ｓ，Ｍｒ＝６２１．７６，最终偏离因子Ｒ＝０．０３５１，ＲＷ２＝０．０７７２，Ｆｌａｃｋ值为０．１（２）．结构分析表明，主客体存在分子间氢键．光学纯的ＴＡＤＤＯＬ与消旋的乙基吡啶亚砜（１）作用时，ＴＡＤＤＯＬ对１具有很好的手性识别能力，选择性地与１的一个对映体形成氢键，长成晶体．参照晶体结构确定了１的两个对映体的绝对构型     

Potassium bromide catalyzed NS bond formation via oxidative dehydrogenation

N-Substituted benzo[d]isothiazol-3(2H)-ones are a family of compounds with extremely important application. Recently, we have developed a new green pathway to synthesize these compounds via potassium bromide-catalyzed intramolecular oxidative dehydrogenative cyclization. This reaction has high functional group tolerance and affords excellent yield even in gram scale.