双亲金属卟啉在SDS胶束中的光谱性质及动力学研究

5,10,15-3(4-羟基酚基)-20-(4-十六烷氧基酚基)卟啉锌(P1Zn)增溶于SDS胶束中,用敏感于微环境变化的紫外-可见光谱,研究了P1Zn在pH正向滴定和逆向滴定过程中Sorer带和Q带的变化与体相pH值的依赖关系。随着pH值由中性变化到强酸性,P1Zn中的锌原子被氢原子取代生成P1,而pH值由强酸性变化到中性,P1中的氢原子并未被锌原子取代生成P1Zn。在中性条件下P1与Zn(Ⅱ)的动力学表明,在pH值变化过程中,其增溶位置可能发生了变化,初步分析了双亲卟啉的结构对于增溶位置的影响。     

布洛芬与人血白蛋白位点II动态结合过程的分子模拟:一种结合途径分析

人血白蛋白（HSA）主要有两个药物结合位点,位点I和位点Ⅱ,许多小分子优先结合在位点Ⅱ上,包括抗炎类药物布洛芬。本文采用分子模拟方法研究了布洛芬小分子与HSA位点Ⅱ结合的动态过程,探讨了二者的结合机制。首先构建了50个随机分布的布洛芬与HSA复合物体系,经50 ns分子动力学模拟,其中一个布洛芬分子稳定结合于位点Ⅱ。基于该分子的运动轨迹分析,发现布洛芬的结合可分为四个阶段,即远程吸引、表面结合调整、进入位点Ⅱ空腔和稳定结合。比较范德华和静电相互作用能,发现初期以静电吸引为主,中期在HSA表面的两个极性区域间调整,逐步转移至位点Ⅱ附近;然后在位点Ⅱ入口处的极性残基和附近疏水残基的共同作用下,布洛芬进入位点Ⅱ空腔;进入空腔后,静电和疏水共同作用形成稳定结合。在结合过程中,位点Ⅱ附近的蛋白表面发生明显改变,体现出一定的“诱导契合”作用,同时分子模拟得到的结合模式和布洛芬-HSA结合的晶体结构类似。结果表明,分子模拟可以辅助研究小分子和蛋白结合的动态过程,从分子水平阐述相关结合机制。     

Unraveling the Role of Site Isolation and Support for Semihydrogenation of Phenylacetylene

Intermetallic compounds (IMCs) composed of transition metals and post‐transition metals function as superior heterogeneous catalysts in comparison to their monometallic and bimetallic alloy counterparts. Rendering IMCs in their nanomaterial iterations further enhances their efficiency. Herein, we demonstrate the role of PdIn as well‐dispersed intermetallic nanoparticles (IMNPs) for the semihydrogenation of phenylacetylene selectively to styrene at ambient conditions. Higher selectivity of PdIn was explained with the help DOS calculations. We have explored the role of a few well‐known silica‐based supports such as SBA‐15 and MCM‐41, providing insight into how they affect catalysis. As an additional support we have explored previously reported JNC‐1, a mesoporous carbon material obtained via a templated strategy using SBA‐15. PdIn supported on SBA‐15 and JNC‐1 displayed the best dispersion, while also exhibiting the most catalytic activity due to the unique nature of the porous structure.     

Site-specific PEGylation of Human Growth Hormone by Mutated Sortase A

Human growth hormone(hGH), a classic therapeutic protein, which promotes growth and wound healing, is released from the pituitary gland. As a protein drug, its short half-life is its main barrier to therapeutic efficacy. Various strategies have been designed to prolong its serum half-life, the most common of which is the conjugation with polyethylene glycol(PEG), as this has been shown to significantly extend protein's serum half-life. However, PEGylation often results in random conjugation, which can lead to impaired protein function and hinder purification, characterization and evaluation of the PEGylated protein. Therefore, site specific PEGylation is a promising direction for PEG-protein conjugation. Here we took advantages of the mutated sortase A(7M) enzyme, which can enzymatically ligate the universal α-amino acids to a C-terminal tagged protein. This then allows specific modification of the C-terminal of hGH with PEG. This site-specific bound PEG-hGH has similar efficacy, receptor binding and cell proliferation as wild-type hGH; however, pharmacokinetic analysis demonstrates that its serum half-life is almost 24 times that of wild-type hGH. Herein, we provided a promising advancement in the development of site specific PEGylated therapeutic proteins.     

High-precision quantitative atomic-site-analysis of functional dopants in crystalline materials by electron-channelling-enhanced microanalysis

Knowledge of the location and concentration of impurity atoms doped into a synthesized material is of great interest to investigate the effect of doping. This would usually be investigated using X-ray or neutron diffraction methods in combination with Rietveld analysis. However, this technique requires a large-scale facility such as a synchrotron radiation source and nuclear reactor, and can sometimes fail to produce the desired results, depending on the constituent elements and the crystallographic conditions that are being analysed. Thus, it would be preferable to use an element-selective spectroscopy technique that is applicable to any combination of elements. We have established a quantitative method to deduce the occupation sites and their occupancies, as well as the site-dependent chemical states of the doped elements, using a combination of transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, and electron energy-loss spectroscopy (EELS). The method is based on electron channelling phenomena where the symmetries of the Bloch waves excited in a crystal are dependent on the diffraction condition or incident beam direction with respect to the crystal axes. By rocking the incident electron beam with a fixed pivot point on the sample surface, a set of EDX/EELS spectra are obtained as a function of the beam direction. This is followed by a statistical treatment to extract the atom-site-dependent spectra, thereby quantitatively enabling the estimation of the site occupancies and chemical states of the dopants. This is an extension of the ‘ALCHEMI’ (Atom Location by Channelling Enhanced Microanalysis) method or ‘HARECXS/HARECES’ (High Angular Resolution Channelled X-ray/Electron Spectroscopy), and we further extended the method to be applicable to cases where the crystal of interest contains multiple inequivalent atomic sites for a particular element, applying the precise spectral predictions based on electron elastic/inelastic dynamical scattering theory. After introduction of conceptual aspects of the method, we describe the extension of the method together with the development of the theoretical calculation method. We then demonstrate several useful applications of the method, including luminescent, ferrite, and battery materials. We discuss the advantages and drawbacks of the present method, compared with those of the recently developed atomic column-by-column analysis using aberration-corrected scanning TEM and high-efficiency X-ray detectors.     

Überraschende Reaktionen von 4,4-Bis(trifluormethyl)-1-oxa-3-azabuta-1,3-dienen: Tandem-Reaktion mit Acrylnitril

Summary 4,4-Bis(trifluoromethyl)-1-oxa-3-azabuta-1,3-dienes and acrylonitrile react in the presence of equimolar amounts of 4-dimethylaminopyridine (DMAP) to give 2:1-adducts. A sequential [4+2] cycloaddition is proposed.

Prof. Dr.Rolf Huisgen zum 75. Geburtstag gewidmet     

A two-time-scale model for hospital patient flow

^** Email: m.ramakrishnan{at}ms.unimelb.edu.au^*** Email: david.sier{at}csiro.au^**** Email: p.taylor{at}ms.unimelb.edu.au Hospitals are currently facing high incidences of ambulancebypass, long waiting lists for elective procedures and a significantproportion of patients experiencing long stays in the emergencydepartment before moving to a bed in a ward. We observe thatthe system of wards and the emergency department in essenceoperates on two time-scales: the wards operate on a time-scaleof days, whereas the state of the emergency department evolveson a much faster time-scale. This observation has motivatedus to construct a two-time-scale model for a hospital system.The faster time-scale is modelled by a continuous time Markovchain, whereas the slower time-scale (ward occupancy) is modelledby a discrete time Markov chain. Given the nature of the system,the state of the wards has a direct impact on the emergencydepartment.     

Structure,microstructure and microhardness of rapidly solidified Smy(FexNi1-x)4Sb12 (x = 0.45, 0.50, 0.70, 1) thermoelectric compounds

Skutterudites are interesting compounds for thermoelectric applications. The main drawback in the synthesis of skutterudites by solidification of the melt is the occurrence of two peritectic reactions requiring long annealing times to form a single phase. Aim of this work is to investigate an alternative route for synthesis, based on rapid solidification by planar flow casting. The effect of cooling rate on phases formation and composition, as well as on structure, microstructure and mechanical properties of the filled Sm_y(Fe_xNi_1-x)₄Sb₁₂ (x = 0.45, 0.50, 0.70, 1) skutterudites was studied. Conversely to slowly cooled ingots, rapidly quenched ribbons show skutterudite as the main phase, suggesting that deep undercooling of the liquid prevents the nucleation of high temperature phases, such as (Fe,Ni)Sb and (Fe,Ni)Sb₂. In as-quenched samples, a slightly out of equilibrium Sm content is revealed, which does not alter the position of the p/n boundary; nevertheless, it exerts an influence on crystallographic properties, such as the cell parameter and the shape of the Sb₄ rings in the structure. As-quenched ribbons show a fine microstructure of the skutterudite phase (grain size of 2–20 μm), which only moderately coarsens after annealing at 873 K for 4 days. Vickers microhardness values (350–400 HV) of the skutterudite phase in as-quenched ribbons are affected by the presence of softer phases (i.e. Sb), which are homogeneously and finely dispersed within the sample. The skutterudite hardens after annealing as a consequence of a moderate grain growth, which limits the matrix effect due to the presence of additional phases.     

甲烷水合物拉曼光谱法研究进展

介绍了甲烷在气相、水合相中的拉曼光谱特征,从水合物生成热力学、生成动力学、分解动力学和分解机理几方面对甲烷水合物实验室拉曼光谱分析和深海拉曼光谱检测的最新进展进行了综述。生成热力学方面重点介绍了基于拉曼光谱技术的水合物生成条件的原位观测、水合物结构的鉴定及水合物孔穴占有率和水合数的求算,生成动力学方面主要介绍了水合物生成过程中孔穴形成随时间的变化关系及水合物形成后流体中甲烷浓度的变化规律等内容。水合物分解方面着重介绍了水合物分解的微观机理、孔穴占有率的变化规律及多孔介质中水合物分解速率表达式。针对目前拉曼光谱法研究水合物存在的问题,对未来的发展方向和重点提出了建议。