Intermolecular insertion of an N,N-heterocyclic carbene into a nonacidic C-H bond: Kinetics, mechanism and catalysis by (K-HMDS)2 (HMDS = Hexamethyldisilazide)

The reaction of 2‐[¹³C]‐1‐ethyl‐3‐isopropyl‐3,4,5,6‐tetrahydropyrimidin‐1‐ium hexafluorophosphate ([¹³C₁]‐ 1 ‐PF₆) with a slight excess (1.03 equiv) of dimeric potassium hexamethyldisilazide (“(K‐HMDS)₂”) in toluene generates 2‐[¹³C]‐3‐ethyl‐1‐isopropyl‐3,4,5,6‐tetrahydropyrimid‐2‐ylidene ([¹³C₁]‐ 2 ). The hindered meta‐stable N,N‐heterocyclic carbene [¹³C₁]‐ 2 thus generated undergoes a slow but quantitative reaction with toluene (the solvent) to generate the aminal 2‐[¹³C]‐2‐benzyl‐3‐ethyl‐1‐isopropylhexahydropyrimidine ([¹³C₁]‐ 14 ) through formal C? H insertion of C(2) (the “carbene carbon”) at the toluene methyl group. Despite a significant pK_a mismatch (ΔpK_a 1 ⁺ and toluene estimated to be ca. 16 in DMSO) the reaction shows all the characteristics of a deprotonation mechanism, the reaction rate being strongly dependent on the toluene para substituent (ρ=4.8(±0.3)), and displaying substantial and rate‐limiting primary (k_H/k_D=4.2(±0.6)) and secondary (k_H/k_D=1.18(±0.08)) kinetic isotope effects on the deuteration of the toluene methyl group. The reaction is catalysed by K‐HMDS, but proceeds without cross over between toluene methyl protons and does not involve an HMDS anion acting as base to generate a benzyl anion. Detailed analysis of the reaction kinetics/kinetic isotope effects demonstrates that a pseudo‐first‐order decay in 2 arises from a first‐order dependence on 2 , a first‐order dependence on toluene (in large excess) and, in the catalytic manifold, a complex noninteger dependence on the K‐HMDS dimer. The rate is not satisfactorily predicted by equations based on the Brønsted salt‐effect catalysis law. However, the rate can be satisfactorily predicted by a mole‐fraction‐weighted net rate constant: ?d[ 2 ]/dt=({x ₂ k_uncat}+{(1?x ₂ ) k_cat})[ 2 ]¹[toluene]¹, in which x ₂ is determined by a standard bimolecular complexation equilibrium term. The association constant (K_a) for rapid equilibrium–complexation of 2 with (K‐HMDS)₂ to form [ 2 (K‐HMDS)₂] is extracted by nonlinear regression of the ¹³C NMR shift of C(2) in [¹³C₁]‐ 2 versus [(K‐HMDS)₂] yielding: K_a=62(±7) M ^?1; δ_C(2) in 2 =237.0 ppm; δ_C(2) in [ 2 (K‐HMDS)₂]=226.8 ppm. It is thus concluded that there is discrete, albeit inefficient, molecular catalysis through the 1:1 carbene/(K‐HMDS)₂ complex [ 2 (K‐HMDS)₂], which is found to react with toluene more rapidly than free 2 by a factor of 3.4 (=k_cat/k_uncat). The greater reactivity of the complex [ 2 (K‐HMDS)₂] over the free carbene ( 2 ) may arise from local Brønsted salt‐effect catalysis by the (K‐HMDS)₂ liberated in the solvent cage upon reaction with toluene.     

129Xe NMR chemical shift in Xe@C60 calculated at experimental conditions: Essential role of the relativity,dynamics, and explicit solvent

The isotropic ¹²⁹Xe nuclear magnetic resonance (NMR) chemical shift (CS) in Xe@C₆₀ dissolved in liquid benzene was calculated by piecewise approximation to faithfully simulate the experimental conditions and to evaluate the role of different physical factors influencing the ¹²⁹Xe NMR CS. The ¹²⁹Xe shielding constant was obtained by averaging the ¹²⁹Xe nuclear magnetic shieldings calculated for snapshots obtained from the molecular dynamics trajectory of the Xe@C₆₀ system embedded in a periodic box of benzene molecules. Relativistic corrections were added at the Breit–Pauli perturbation theory (BPPT) level, included the solvent, and were dynamically averaged. It is demonstrated that the contribution of internal dynamics of the Xe@C₆₀ system represents about 8% of the total nonrelativistic NMR CS, whereas the effects of dynamical solvent add another 8%. The dynamically averaged relativistic effects contribute by 9% to the total calculated ¹²⁹Xe NMR CS. The final theoretical value of 172.7 ppm corresponds well to the experimental ¹²⁹Xe CS of 179.2 ppm and lies within the estimated errors of the model. The presented computational protocol serves as a prototype for calculations of ¹²⁹Xe NMR parameters in different Xe atom guest–host systems. © 2013 Wiley Periodicals, Inc.     

On the molecular mechanism of ion specific Hofmeister series

Hofmeister series ranks the ability of salt ions in influencing a variety of properties and processes in aqueous solutions.In this review,we reexamine how these ions and some other small molecules affect water structure and thermodynamic properties,such as surface tension and protein backbone solvation.We illustrate the difficulties in interpreting the thermodynamic information based on structural and dynamic arguments.As an alternative,we show that the solvation properties of ions and proteins/small molecules can be used to explain the salt effects on the thermodynamic properties of the solutions.Our analysis shows that the often neglected cation-anion cooperativity plays a very important role in these effects.We also argue that the change of hydrogen donor/acceptor equilibrium by added cosolutes/cosolvents can be used to explain their effects on protein secondary structure denaturation/protection:those increase hydrogen donor concentrations such as urea and salts with strongly solvated cations/weakly hydrated anions tend to dissolve protein backbone acting as secondary structure denaturants,whereas those lack of hydrogen donors but rich in acceptors have the opposite effect.     

我国国债规模对宏观经济影响实证分析

随着以希腊债务危机为导火索的欧洲债务危机的愈演愈烈,国债对宏观经济的影响再一次成为了经济学讨论的热点.首先从直观图形着手,运用H-P滤度法去除趋势后,计算各变量的偏离趋势百分比,对比国债规模代替变量与宏观经济效应代替变量之间的偏离趋势图,从图形得到的定量关系为后面的实证分析做好准备.然后进一步进行协整分析,并在向量自回归(VAR)框架下通过脉冲响应函数考察变量之间的相互影响路径,最后通过建立误差修正模型(ECM)分析各个变量之间的长期均衡关系和短期波动特征,以量化各变量之间影响程度的大小.全面系统地研究了国债对宏观经济增长的影响程度并做出实证分析,对于深刻认识国债的本质,规避国债的风险,科学合理地制定国债政策有着重要的理论价值和实际意义.     

End Capping Alters the Structural Characteristics and Mechanical Properties of Transthyretin (105–115) Amyloid Protofibrils

Pathological amyloid proteins are associated with degenerative and neurodegenerative diseases. These amyloid proteins develop as oligomer, fibrillar, and plaque forms, due to the denatured and unstable status of the amyloid monomers. Specifically, the development of fibrillar amyloid proteins has been investigated through several experimental studies. To understand the generation of amyloid fibrils, environmental factors such as point mutations, pH, and polymorphic characteristics have been considered. Recently, amyloid fibril studies related to end‐capping effects have been conducted to understand amyloid fibril development. However, atomic‐level studies to determine the stability and mechanical properties of amyloid fibrils based on end capping have not been undertaken. In this study, we show that end capping alters the structural characteristics and conformations of transthyretin (TTR) amyloid fibrils by using molecular dynamics (MD) simulations. Variation in the structural conformations and characteristics of the TTR fibrils through end capping are observed, due to the resulting electrostatic energies and hydrophobicity characteristics. Moreover, the end capping changes the mechanical properties of TTR fibrils. Our results shed light on amyloid fibril formation under end‐capping conditions.     

任意阶标度分形格分抗与非正则格型标度方程

Carlson分形格电路是分抗的理想逼近情形,但仅具有负半阶运算性能,逼近效益随着电路节次数的增加逐渐降低.虽然可嵌套得到-1/2~n阶(n为大于或等于2的整数)分抗逼近电路,但结构复杂,无法实现任意分数阶运算.通过类比拓展Carlson分形格电路,获得具有高逼近效益的任意实数阶微积算子的分抗逼近电路——标度分形格分抗,并用非正则格型标度方程进行数学描述.分别探讨非正则格型标度方程的近似求解和真实解.通过调节电阻递进比α与电容递进比β的取值,可构造出具有任意运算阶的标度分形格分抗逼近电路.标度拓展极大地提高了标度分形格分抗电路的逼近效益.随着标度因子的增加,负半阶标度分形格分抗的逼近效益逐渐增大并明显高于Carlson分形格分抗.设计了基于五节Carlson分形格分抗与负半阶标度分形格分抗的半阶微分运算电路,并对周期三角波和周期方波信号进行半阶微分运算,实验测试结果与理论分析一致.     

综合评价中异常值的识别及无量纲化处理方法

针对综合评价中的异常值现象,讨论了原始数据中是否存在异常值、若存在异常值该如何识别异常值以及对含有异常值的评价数据如何进行无量纲化处理三个问题。关于异常值的判断与识别,给出了以“中位数”为参考点,通过比较排序后两端数据偏离中位数的距离的处理思路。对含有异常值的评价数据的无量纲化处理问题,基于常用的“极值处理法”,通过分别指定异常值和非异常值无量纲化取值区间的方式,提出了一种分段的无量纲化处理方法。最后,通过与已有文献异常值识别及无量纲化处理结果的对比分析,验证了本文方法的有效性,发现本文给出的方法能够实现对异常值的适度筛选,且能够提升无量纲化数据分布均衡性。     

Influence of adsorption effects on retention indices of selected C10-hydroxy compounds at various temperatures

Summary Retention indices of 6 selected hydroxy compounds (aliphatic and bicyclic alcohols, phenols) were determined on 2 HP-5 fused-silica, capillary columns with different film thicknesses (0.11 m and 0.33 m) at 8 different oven temperatures between 80 and 150°C. For some substances the I-T plot was found to show a minimum which cannot be explained by the common retention-index temperature-dependence in gas-liquid chromatography. This result is discussed in terms of adsorption at the liquid-solid interface of the capillary column.     

Cover Picture: QM/MM Car‐Parrinello Molecular Dynamics Study of the Solvent Effects on the Ground State and on the First Excited Singlet State of Acetone in Water (ChemPhysChem 11/2003)

The cover picture shows …?‥the solvent effect of water upon the lowest‐lying singlet excitation in acetone. The transition, which involves the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), is blue‐shifted in water (sol) with respect to the gas phase (vac), since the HOMO is stronger stabilized in water than the LUMO. The authors calculate the absorption and fluorescence spectra of acetone in water with a hybrid Car–Parrinello quantum chemical/classical molecular dynamics approach and investigate the influence of the solvent. The lower part of the picture shows the excitation energy during a simulation. One configuration with a very high excitation energy (three hydrogen bonds, short C?O bond) and one configuration with a very low excitation energy (two hydrogen bonds, long C?O bond) are shown in detail. Find out more in the article by Rothlisberger and co‐workers on pages pp. 1177–1182.     

Synergistic Effects of Lewis Bases and Substituents on the Electronic Structure and Reactivity of Boryl Radicals

Boryl radicals have the potential for the development of new molecular entities and for application in new radical reactions. However, the effects of the substituents and coordinating Lewis bases on the reactivity of boryl radicals are not fully understood. By using first‐principles methods, we investigated the spin‐density distribution and reactivity of a series of boryl radicals with various substituents and Lewis bases. The substituents, along with the Lewis bases, only affect the radical reactivity when an unpaired electron is in the boron p_z orbital, that is, for three‐coordinate radicals. We found evidence of synergistic effects between the substituents and the Lewis bases that can substantially broaden the tunability of the reactivity of the boryl radicals. Among Lewis bases, pyridine and imidazol‐2‐ylidene show a similar capacity for stabilization by delocalizing the spin density. Electron‐donating substituents, such as nitrogen, more efficiently stabilize boryl radicals than oxygen and carbon atoms. The reactivity of a boryl radical is always boron based, irrespective of the spin density on boron.