关于-RTlnK_c~■=Δ_rG_m~■(c~■)的讨论

在等温等压条件下,通过pB=cBRT关系转换,所得关系式证明了-RTlnK—cΟ=ΔrG—mΟ(c—Ο)。还分析推证出ΔrG—mΟ(c—Ο)和ΔrG—mΟ(p—Ο)、ΔrH—Οm(c—Ο)和ΔrHΟ—m(p—Ο)、ΔrSΟ—m(c—Ο)和ΔrSΟ—m(p—Ο)、ΔrUΟ—m(c—Ο)和ΔrHΟ—m(cΟ—)以及ΔrG—Οm(c—Ο)和ΔrA—mΟ(c—Ο)之间的几个关系式,进一步证实了-RTlnK—cΟ=ΔrGΟ—m(c—Ο)。     

Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions

Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S_NAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.     

Clean one-pot synthesis of 1,2,4-oxadiazoles under solvent-free conditions using microwave irradiation and potassium fluoride as catalyst and solid support

Potassium fluoride was found to be an efficient catalyst and solid support for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles. In this work, a one-pot method for the synthesis of these compounds from the reaction of nitriles with hydroxylamine hydrochloride and acyl chloride in the presence of potassium fluoride under solvent-free conditions using microwave irradiation has been developed. The advantages of using potassium fluoride as a solid support in comparison to conventional solid supports are simple operation and convenient separation of the products.     

Permanent antistatic phthalocyanine/epoxy nanocomposites - Influence of crosslinking agent, solvent and processing temperature

Cross-linked epoxy matrices containing small amounts of semi-conductive phthalocyanine (Phthalcon) nanoparticles were prepared using different crosslinking agents and processing temperatures. A starting mixture containing an optimum dispersion of these nanoparticles and with an almost equal and large Hamaker constant was always used. Nevertheless large differences in the relation between the volume conductivity σ_v and the particle concentration φ were found and this relation appeared to be sensitive to small changes in processing temperature and the application of a post-cure. Also the amine crosslinker chosen and the initial amount of solvent (catalyst) in the starting dispersion had a major effect. It was shown that these changes influence strongly the formation of and the final conductive fractal particle network morphology through the polymer matrix. During processing a local relaxation of the initially formed fractal particle network into another fractal particle network was often observed, which introduced or enlarged the amount of isolating material between the particles of the conductive network and changed the fractality and structure of the conductive backbone of the particle network. This local relaxation lowered the σ_v at each phthalcon concentration and enlarged φ_c by several orders of magnitude. The occurrence of local relaxation is dependent on the rate of viscosity change during the crosslinking of the polymer matrix components, the way the fractal conductive particle network is formed during processing (universal or non-universal) and the amount of solvent present. Local relaxation may even occur after the gel point of the polymer matrix. A severe post-cure may be needed to stop this local relaxation. To our knowledge local relaxation of a (fractal) nanoparticle network in a polymer matrix during processing is a new phenomenon, not reported before for polymer composites containing (conductive) nanoparticles.     

TiO2 as a Reusable Catalyst for the One‐Pot Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐ones under Solvent‐Free Conditions

An efficient solvent‐free method for the synthesis of various 3,4‐dihydropyrimidin‐2(1H)‐ones using TiO₂ as a recyclable heterogeneous catalyst is described. Compared to known methods, satisfactory results are obtained with excellent yields, short reaction times, and simplicity in the experimental procedure.     

稀醋酸/水溶液中单个醋酸与水分子的氢键结构

在醋酸/水体系的工业分离中,溶液中的氢键对分离效率有很大影响.本文采用两种第一性原理方法,即从头算分子动力学模拟(AIMD)和量子化学计算(QCC),对由单个醋酸和不同水分子所组成聚合体的氢键相互作用进行了研究,采用极化统一模型和自洽反应场模型计算得到了聚合体在水溶液中的热力学数据.从QCC计算的气相和水溶液中的聚合自由能表明六元环在两种状态下都为最优结构,热力学数据反映出的各种结构的相对稳定性与AIMD模拟的环分布符合得相当一致.研究表明,由于存在醋酸和水分子间的氢键作用,稀醋酸/水溶液中的醋酸分离要比在浓醋酸溶液中困难得多.     

Multiple ligand simultaneous docking: Orchestrated dancing of ligands in binding sites of protein

Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein–ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl‐xL complex with ABT‐737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single‐ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X‐ray crystallographic maps, and aiding fragment‐based drug design, respectively. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Protegrin‐1 orientation and physicochemical properties in membrane bilayers studied by potential of mean force calculations

Protegrin‐1 (PG‐1) belongs to the family of antimicrobial peptides. It interacts specifically with the membrane of a pathogen and kills the pathogen by releasing its cellular contents. To fully understand the energetics governing the orientation of PG‐1 in different membrane environments and its effects on the physicochemical properties of the peptide and membrane bilayers, we have performed the potential of mean force (PMF) calculations as a function of its tilt angle at four distinct rotation angles in explicit membranes composed of either DLPC (1,2‐dilauroylphosphatidylcholine) or POPC (1‐palmitoyl‐2‐oleoylphosphatidylcholine) lipid molecules. The resulting PMFs in explicit lipid bilayers were then used to search for the optimal hydrophobic thickness of the EEF1/IMM1 implicit membrane model in which a two‐dimensional PMF in the tilt and rotation space was calculated. The PMFs in explicit membrane systems clearly reveal that the energetically favorable tilt angle is affected by both the membrane hydrophobic thickness and the PG‐1 rotation angle. Local thinning of the membrane around PG‐1 is observed upon PG‐1 tilting. The thinning is caused by both hydrophobic mismatch and arginine‐lipid head group interactions. The two‐dimensional PMF in the implicit membrane is in good accordance with those from the explicit membrane simulations. The ensemble‐averaged Val16 ¹⁵N and ¹³CO chemical shifts weighted by the two‐dimensional PMF agree fairly well with the experimental values, suggesting the importance of peptide dynamics in calculating such ensemble properties for direct comparison with experimental observables. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Accurate free energy calculation along optimized paths

The path‐based methods of free energy calculation, such as thermodynamic integration and free energy perturbation, are simple in theory, but difficult in practice because in most cases smooth paths do not exist, especially for large molecules. In this article, we present a novel method to build the transition path of a peptide. We use harmonic potentials to restrain its nonhydrogen atom dihedrals in the initial state and set the equilibrium angles of the potentials as those in the final state. Through a series of steps of geometrical optimization, we can construct a smooth and short path from the initial state to the final state. This path can be used to calculate free energy difference. To validate this method, we apply it to a small 10‐ALA peptide and find that the calculated free energy changes in helix‐helix and helix‐hairpin transitions are both self‐convergent and cross‐convergent. We also calculate the free energy differences between different stable states of β‐hairpin trpzip2, and the results show that this method is more efficient than the conventional molecular dynamics method in accurate free energy calculation. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010