Enzyme Models—From Catalysis to Prodrugs

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.     

A general formula for analytic reduction of multi-loop tensor Feynman integrals

We prove a general formula for analytic reduction of tensor integrals which appear in calculations of multi-loop Feynman diagrams in quantum field theory models.     

Adjoint‐based airfoil optimization with discretization error control

In this article, we develop a new airfoil shape optimization algorithm based on higher‐order adaptive DG methods with control of the discretization error. Each flow solution in the optimization loop is computed on a sequence of goal‐oriented h‐refined or hp‐refined meshes until the error estimation of the discretization error in a flow‐related target quantity (including the drag and lift coefficients) is below a prescribed tolerance. Discrete adjoint solutions are computed and employed for the multi‐target error estimation and adaptive mesh refinement. Furthermore, discrete adjoint solutions are employed for evaluating the gradients of the objective function used in the CGs optimization algorithm. Furthermore, an extension of the adjoint‐based gradient evaluation to the case of target lift flow computations is employed. The proposed algorithm is demonstrated on an inviscid transonic flow around the RAE2822, where the shape is optimized to minimize the drag at a given constant lift and airfoil thickness. The effect of the accuracy of the underlying flow solutions on the quality of the optimized airfoil shapes is investigated. Copyright © 2014 John Wiley & Sons, Ltd.     

Analytical solution to dielectric droplet diffusiophoresis under Debye–Hückel approximation

A simple analytical formula is obtained for the diffusiophoresis of a dielectric fluid droplet in symmetric binary electrolyte solutions under Debye–Hückel approximation valid for weakly charged droplets. The chemiphoresis is found to yield negative mobilities most of the time for droplets of constant surface charge density, which implies that the droplets tend to move away from the source releasing ionic chemicals. This is undesirable in some practical applications like drug delivery with liposomes in terms of conveying the drug-carrying liposomes to the desired area in the human body releasing specific ionic chemicals utilizing the self-guiding nature of diffusiophoresis. The further involvement of the electrophoresis component, however, may change the scenario via the oriented electric field generated by the induced diffusion potential. The lesson here is that while the impact of the chemiphoresis component is determined by nature and uncontrollable, the electrophoresis component serves as an artificially adjustable factor via choosing droplets with the surface charge of appropriate sign in practical applications. The results here have potential use in practical applications such as drug delivery. The portable simple analytical formula is a powerful asset to experimental researchers and design engineers in colloid science and technology to facilitate their works.     

融入统筹理念的分析化学实验教学

基于一流创新人才培养的要求和分析化学实验课程的特点,介绍了如何在分析化学实验教学中融入统筹学理念,旨在培养学生的统筹能力,拓展化学实验课程的育人功能,实现知识技能传授和综合能力培养并重的教学目的,将创新人才培养的教学理念落到实处。     

IL-18与IL-18R分子对接计算发展模拟蛋白质互作研究方法

研究蛋白质互作的化学生物学方法主要有荧光共振能量转移(Fluorescence resonance energy transfer, FRET)、酵母双杂交(Yeast two-hybrid technology, YTH)、免疫共沉淀(Co-immunoprecipitation, Co-IP)等。在此基础上,为了发展一种新的研究生物大分子互作,特别是膜蛋白相互作用的定量计算方法,依据前期研究发现,应用ELISA方法与QAH-NEU-1定量芯片技术检测NLRP2:ShRNAs慢病毒(Lentivirus)感染人脑微血管内皮细胞(Human brain microvascular endothelial cells, HBMEC), 敲除(Knocking down)NLRP2基因后的IL-18的分泌量与对照组比较, 显著提高(IL-18: 998 pg/mL),表明它在炎症免疫中起关键调控作用。本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R互作的空间结构与构象变化,计算找到了相互作用界面的氨基酸的一级序列与二级结构,以及它们之间的相互作用力,并用拉氏图评估对接构象,研究发现B亚基在IL-18与IL-18R的结合中起主要作用。该计算方法与实验方法比较,可快速找到蛋白-蛋白相互作用的构象空间,优化膜蛋白互作的精度;能从原子与量子水平探究细胞因子与膜蛋白受体的互作;更深入解析分子机理,数据精确定量。研究结果表明本文应用ZDOCK算法建立了通过计算模拟膜蛋白生物大分子互作的新领域,为细胞因子与化学因子的多肽类药物开发提供新的思路; 为细菌病毒感染/肿瘤疾病的防治提供科学理论依据; 在分子识别,神经元网络深度学习,生物信息处理领域具有广泛的应用。     

Nitrogen reduction reaction to ammonia at ambient conditions: A short review analysis of the critical factors limiting electrocatalytic performance

The direct electrocatalytic production of ammonia (NH₃) from N₂ and H₂O at ambient conditions is one of today's chemical challenges to meet the growing industrial demand for ammonia. Despite numerous studies on designing novel catalysts to activate N₂ molecule and elucidating the reaction mechanism, many critical factors (such as gas diffusion and charge transfer limitations that instead promote the side reaction of hydrogen evolution) remain unsolved, suggesting that a breakthrough is needed to improve performance in this challenging reaction. Based on this, we review here recent studies that propose advanced solutions, focusing on: (i) the adoption of a three-dimensional nanoarchitecture of the electrode surface (to favour multi-electron transfer), (ii) the design of cell configuration (including the development of gas diffusion electrodes – GDEs), (iii) the critical aspects of the more efficient lithium-mediated approach in non-aqueous solvents (flooding of the GDE, sustainability of the proton-shuttle system), (iv) new methods for ammonia detection avoiding false positive.     

Study of the Deflection Angle and Shadow of Black Hole Solutions in Non-Plasma and Plasma Mediums Under the Effect of Einstein–Gauss–Bonnet Gravity

In this paper, the Gibbons and Werner technique is used to calculate the weak deflection angle for the black hole solution under the effects of Einstein–Gauss–Bonnet gravity. The Gauss–Bonnet theorem in the limits of weak field is used to evaluate the Gaussian optical curvature in order to obtain the results. The visual effects of the deflection angle on the impact parameter is also looked at and the smallest radius in the non-plasma/plasma medium. Moreover, in order to check the consistency of the results concerning the weak deflection angle, the Keeton and Petters approach is applied to study the deflection angle, which is the expansion of series with a single mass variable, which can be directly addressed by using the post–post Newtonian framework. Furthermore, the deflection angle and shadow under the influence of the plasma is examined by using the motion of particle in a non-magnetized plasma and pressure-free plasma medium as described by the new ray-tracing algorithm. It is shown that plasma as well as Einstein–Gauss-Bonnet gravity corrections are affected by shadows.     

预先合成量子点组装制备高效量子点太阳电池

量子点太阳电池现已成为极具潜力的“第三代” 光伏器件, 其优点体现在材料成本低廉, 制备工艺简便, 以及其敏化剂特有的多激子效应(MEG) 潜能和吸光范围可方便调节等方面. 但是与染料分子敏化剂相比, 量子点敏化剂粒径更大、表面缺乏具有与TiO₂结合的官能团, 这导致其在TiO₂介孔中渗透阻力大、难以在TiO₂表面吸附沉积, 所以量子点沉积手段在电池组装过程中尤为重要. 本文综述了电池组装过程中量子点的沉积方法, 分类阐述了直接生长量子点方法: 化学浴沉积(CBD)和连续离子层吸附生长(SILAR), 以及采用预先合成量子点的沉积方法: 连接分子辅助法(LA)、直接吸附法(DA)和电泳沉积(EPD)方法, 陈述了各沉积方法的发展过程及相应电池性能的改善, 对比了这些沉积方法的优缺点. 突出介绍了预先合成量子点的沉积方法, 特别是近年来不断优化而凸显优势的连接分子辅助法(LA). 总结了此方法快速、均匀沉积以及实现器件高性能的特点, 介绍了此方法沉积表面缺陷更少、结构更完善、材料更“绿色化”的量子点敏化剂的最新研究成果.     

Schwinger-boson approach to anisotropy ferrimagnetic chain with bond alternation

We use the Schwinger-boson approach to study the anisotropy ferrimagnetic spin-(1/2,1) chain with bond alternation.Based on the effect of bond alternation δ,we obtain energy gap,free energy,and specific heat,respectively.The specific heat with larger bond alternation(δ 0.7) displays a peak at low temperature.Based on the effect of XXZ anisotropy parameter δ,we present excited spectrums,free energy,and specific heat,respectively.