Prediction and analysis of structure,stability and unfolding of thermolysin-like proteases

Summary Bacillus neutral proteases (NPs) form a group of well-characterized homologous enzymes, that exhibit large differences in thermostability. The three-dimensional (3D) structures of several of these enzymes have been modelled on the basis of the crystal structures of the NPs ofB. thermoproteolyticus (thermolysin) andB. cercus. Several new techniques have been developed to improve the model-building procedures. Also a model-building by mutagenesis' strategy was used, in which mutants were designed just to shed light on parts of the structures that were particularly hard to model. The NP models have been used for the prediction of site-directed mutations aimed at improving the thermostability of the enzymes. Predictions were made using several novel computational techniques, such as position-specific rotamer searching, packing quality analysis and property-profile database searches. Many stabilizing mutations were predicted and produced: improvement of hydrogen bonding, exclusion of buried water molecules, capping helices, improvement of hydrophobic interactions and entropic stabilization have been applied successfully. At elevated temperatures NPs are irreversibly inactivated as a result of autolysis. It has been shown that this denaturation process is independent of the protease activity and concentration and that the inactivation follows first-order kinetics. From this it has been conjectured that local unfolding of (surface) loops, which renders the protein susceptible to autolysis, is the rate-limiting step. Despite the particular nature of the thermal denaturation process, normal rules for protein stability can be applied to NPs. However, rather than stabilizing the whole protein against global unfolding, only a small region has to be protected against local unfolding. In contrast to proteins in general, mutational effects in proteases are not additive and their magnitude is strongly dependent on the location of the mutation. Mutations that alter the stability of the NP by a large amount are located in a relatively weak region (or more precisely, they affect a local unfolding pathway with a relatively low free energy of activation). One weak region, that is supposedly important in the early steps of NP unfolding, has been determined in the NP ofB. stearothermophilus. After eliminating this weakest link a drastic increase in thermostability was observed and the search for the second-weakest link, or the second-lowest energy local unfolding pathway is now in progress. Hopefully, this approach can be used to unravel the entire early phase of unfolding.     

Two Aluminophosphate Molecular Sieves Built from Pairs of Enantiomeric Structural Building Units

Herein we report the synthesis and structures of two new small‐pore aluminophosphate molecular sieves PST‐13 and PST‐14 with mutually connected 8‐ring channels. The structure of PST‐13, synthesized using diethylamine as an organic structure‐directing agent, contains penta‐coordinated framework Al atoms bridged by hydroxy groups and thus edge‐sharing 3‐ and 5‐rings. Upon calcination, PST‐13 undergoes a transformation to PST‐14 with loss of bridging hydroxy groups and occluded organic species. The structures of both materials consist “nonjointly” of pairs of previously undiscovered 1,5‐ and 1,6‐open double 4‐rings (d4rs) which are mirror images of each other. We also present a series of novel chemically feasible hypothetical structures built from 1‐open d4r (sti) or 1,3‐open d4r (nsc) units, as well as from these two enantiomeric structural building units.     

Synthesis,crystal structure and photophysical properties of 1,4‐bis(1,3‐diazaazulen‐2‐yl)benzene: a new π building block

A dimerized 1,3‐diazaazulene derivative, namely 1,4‐bis(1,3‐diazaazulen‐2‐yl)benzene [or 2,2′‐(1,4‐phenylene)bis(1,3‐diazaazulene)], C₂₂H₁₄N₄, (I), has been synthesized successfully through the condensation reaction between 2‐methoxytropone and benzene‐1,4‐dicarboximidamide hydrochloride, and was characterized by ¹H NMR and ¹³C NMR spectroscopies, and ESI–MS. X‐ray diffraction analysis reveals that (I) has a nearly planar structure with good π‐electron delocalization, indicating that it might serve as a π building block. The crystal belongs to the monoclinic system. One‐dimensional chains were formed along the a axis through π–π interactions and adjacent chains are stabilized by C—H…N interactions, forming a three‐dimensional architecture. The solid emission of (I) in the crystalline form exhibited a 170 nm red shift compared with that in the solution state. The observed optical bandgap for (I) is 3.22 eV and a cyclic voltammetry experiment confirmed the energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). The calculated bandgap for (I) is 3.37 eV, which is very close to the experimental result. In addition, the polarizability and hyperpolarizability of (I) were appraised for its further application in second‐order nonlinear optical materials.     

Synthesis and Crystal Structure of a New μ-Oxamide Trimeric Hetero-tetranuclear Complex

1 INTRODUCTION The study of spin exchange interaction between metal centers through extended bridges is an active subject in the field of coordination chemistry[1～3]. Polynuclear complexes with extended ligand bri- dges are currently of considerable interest[4～6]. One of the best strategies to design and synthesize poly- nuclear species is ‘complex as ligand’ approach[4, 7]. The oxamide group is proved to be an interesting multiatomic bridge, linking metals in polynuclear complexes[8…     

Molecular mechanics and dynamics study of DNA-furocoumarins complexes: Effect of methylation of the angular derivatives on the intercalation geometry

Summary Results of molecular mechanics calculations on intercalation complexes between DNA and angelicin derivatives: angelicin, 4-methylangelicin, 5-methylangllicin, 4,4-dimethylangelicin, 4,5-dimethylangelicin, 4,6,4-trimethylangelicin and 4,6,5-trimethylangelicin, are presented. The correlation between the presence of methyl groups and an increase in DNA photobinding affinity is discussed on the basis of the molecular structures. The influence of the orientation of the angelicins within the intercalation cavity is also discussed. Finally, the consequences of the dynamical behaviour of angelicin in the intercalation cite are studied.Abbreviations CNDO complete neglect of differential overlap - NMR nuclear magnetic resonance - rms root mean square - UV-A ultraviolet light of class A (320<<400 nm)     

Electron－rich Polynuclear Transition Metal Clusters：Ⅱ．Synthetic and Structural Studies of Some Polynuclear Coinage Metal Cluster Compounds

Ｅｌｅｃｔｒｏｎ－ｒｉｃｈＰｏｌｙｎｕｃｌｅａｒＴｒａｎｓｉｔｉｏｎＭｅｔａｌＣｌｕｓｔｅｒｓ：Ⅱ．ＳｙｎｔｈｅｔｉｃａｎｄＳｔｒｕｃｔｕｒａｌＳｔｕｄｉｅｓｏｆＳｏｍｅＰｏｌｙｎｕｃｌｅａｒＣｏｉｎａｇｅＭｅｔａｌＣｌｕｓｔｅｒＣｏｍｐｏｕｎｄｓＨ...     

Two Novel Lanthanide Metal‐Organic Frameworks Constructed by Tetracarboxylate Ligands: Synthesis,Structures; and Luminescent Properties

Two new isostructural lanthanide metal‐organic frameworks were synthesized using lanthanide oxides and 3,3,4,4‐benzophenonetetracarboxylic acid (H₄BPTC), namely, [Ln(BPTC)(H₂O)_2.5] [Ln = Eu ( 1 ), Gd ( 2 )] under hydrothermal conditions. 1 and 2 revealed porous three‐dimensional structures, possessing a binodal 4, 8‐connected flu network defined by dinuclear building units. 1 and 2 were characterized by powder X‐ray diffraction (PXRD), thermogravimetric analysis (TG), infrared radiation (IR), and photoluminescence (PL) spectra. Furthermore, 1 exhibits red‐light emission under UV light irradiation and the sharp light can be easily observed by naked eyes.     

高中化学“乙醛性质”的项目式教学*——解酒药的研制

以“解酒药的研制”为项目主题,开展高中化学“乙醛性质”的教学。学生通过完成“药物研发分析”“探秘致命物质,寻找救治办法”“药物新构想”等3个项目任务,掌握了乙醛的性质及其应用,构建了有机物结构分析和性质预测的思维模型,学会了对陌生有机物的分析与研究。运用手持技术数字化实验测定溶液酸碱性确定反应机理,锻炼了科学探究、合作交流、思维表达的能力。与课外活动有效整合、实验室仪器与试剂的保障、资料查阅、外援专家指导等是顺利完成本项目教学的关键。     

含氟内酯化合物的合成方法研究进展

内酯化合物广泛存在于天然产物和具有生理活性的物质中, 因此, 内酯化合物的合成一直是人们非常关心的一个研究领域, 不仅作为天然产物的重要合成砌块, 也用来合成一些精细化工产品和医药中间体. 将氟原子或含氟基团引入到内酯化合物分子中, 可使其生理活性发生改变. 就含氟内酯化合物合成方法的研究进展进行了综述.     

Synthesis of Novel,Chiral Bicyclo[3.1.0]hex‐2‐ene Amino Acid Derivatives as Useful Synthons in Medicinal Chemistry

A short and concise synthesis of novel, chiral bicyclo[3.1.0]hex‐2‐ene amino acid derivatives 13 and 14 has been developed. The key step is a stereo‐ and regioselective allylic amination of exo‐ and endo‐methyl bicyclo[3.1.0]hex‐2‐ene‐6‐carboxylates 8 and 9 , which were prepared from 7,7‐dichlorobicyclo[3.2.0]hept‐2‐en‐6‐one ( 1 ). These amino acid derivatives are useful building blocks in medicinal chemistry and can be prepared as chiral compounds by using either (+)‐ 1 or (?)‐ 1 as starting material.