Role of binding entropy in the refinement of protein-ligand docking predictions: analysis based on the use of 11 scoring functions

We present results of testing the ability of eleven popular scoring functions to predict native docked positions using a recently developed method (Ruvinsky and Kozintsev, J Comput Chem 2005, 26, 1089) for estimation the entropy contributions of relative motions to protein-ligand binding affinity. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We use a test set of 100 PDB protein-ligand complexes and ensembles of 101 docked positions generated by (Wang et al. J Med Chem 2003, 46, 2287) for each ligand in the test set. To test the suggested method we compared the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock scoring function, by 2-25% with G-Score, by 7-41% with D-Score, by 0-8% with LigScore, by 1-6% with PLP, by 0-12% with LUDI, by 2-8% with F-Score, by 7-29% with ChemScore, by 0-9% with X-Score, by 2-19% with PMF, and by 1-7% with DrugScore. We also compared the performance of the suggested method with the method based on ranking by cluster occupancy only. We analyze how the choice of a clustering-RMSD and a low bound of dense clusters impacts on docking accuracy of the scoring methods. We derive optimal intervals of the clustering-RMSD for 11 scoring functions.     

Einsatz der flammenlosen Atom-Absorption (Graphitrohrküvette) zur Bestimmung von Kupferspuren in Stahl und anderen Metall-Legierungen nach Extraktion

The determination of small and smallest amounts of copper in steel and other metal alloys by atomic absorption spectroscopy was investigated. It has been found, that the interferences caused by accompanying elements in the determination in aqueous solution with the flame can be completely removed by extracting the copper with Pb-DDTC in chloroform and determining this extract with the heated graphite atomizer. Moreover, it was recognised, that working with the heated graphite atomizer in organic solutions shows great advantages compared with the flame, because any solvent may be used. The methods of continuous variation by Job and the molar ratio by Yoe and Jones for the determination of the complex stoichiometry were transferred to the system Cu-DDTC by working with the heated graphite atomizer.     

酶促开环聚合与自缩合乙烯基共聚合相结合制取超支化聚合物

在Novozyme 435脂肪酶催化下, 甲基丙烯酸羟乙酯(HEMA)引发己内酯(ε-CL)开环聚合反应, 得到一端为双键, 另一端为羟基的直链聚己内酯(PCL)产物; 将其端羟基官能化得到大分子AB*型单体, 与苯乙烯以原子转移自由基聚合(ATRP)反应形式进行自缩合乙烯基共聚合, 得到超支化结构聚苯乙烯-b-聚己内酯产物.     

固相萃取光度法测定饮用水中挥发酚的研究

研究了用Waters Sep-Park-C18小柱固相萃取光度法测定饮用水中挥发酚的方法。水样中经水汽蒸馏分离后的挥发酚，用4－氨基安替比林显色，显色产物可用C18固相萃小柱萃取、乙醇洗脱后用分光光度法测定。方法污染小，操作简便，便于批量样品处理，用于饮用水中挥发酚的测定，结果令人满意。     

丹曲林钠杂质B的合成

以5-对硝基苯胺为原料,与糠醛经重氮化反应制得5-对硝基苯基糠醛(1);1与1-氨基乙内酰脲盐酸盐经缩合、精制得丹曲林(2);2与甲醇钠成盐制得丹曲林钠(3);3在氢氧化钠水溶液中加热条件下,经开环水解制得丹曲林钠杂质B钠盐,再经盐酸酸化、精制合成了丹曲林钠杂质B,总收率16.9%,纯度99.9%,其结构经1H NMR,IR和MS(ESI)确证。     

2-(Prenyloxymethyl)benzoyl (POMB) group: a new temporary protecting group removable by intramolecular cyclization

2-(Prenyloxymethyl)benzoates can be prepared from alcohols and readily available 2-(prenyloxymethyl)benzoic acid by standard acylation techniques or by Mitsunobu reaction with inversion of configuration. The POMB group can be cleaved first by oxidative removal of the prenyl group with DDQ followed by lactonization with expulsion of the alcohol catalyzed by Yb(OTf)₃. These reaction conditions are compatible with the presence of a large number of common protecting groups.     

Incorporation of Co(II) in dealuminated BEA zeolite at lattice tetrahedral sites evidenced by XRD, FTIR, diffuse reflectance UV-Vis, EPR, and TPR

A CoSiBEA zeolite is prepared by a two-step postsynthesis method that consists of first creating vacant T-sites with associated silanol groups by dealumination of TEABEA zeolite with nitric acid and then impregnating the resulting SiBEA zeolite with an aqueous solution of Co(NO3)2. The incorporation of Co into lattice sites of SiBEA is evidenced by XRD. The consumption of OH groups is monitored by FTIR. The presence of Co in its II oxidation state and in tetrahedral coordination is evidenced by diffuse reflectance UV-vis and EPR spectroscopy. The very high reduction temperature (1120 K) of cobalt in CoSiBEA zeolite determined by TPR confirms that Co interacts strongly with the zeolite support, consistent with lattice tetrahedral (T(d)) coordination.     

Zur reaktionvon cyclotri- und cyclotri- und cyclotetrasilazanen mit silylfluoriden

Fluorosilyl substituted cyclosilazanes are formed by treating lithium salts of hexamethylcyclotri- and octa-methylcyclotetrasilazanes with silicon tetrafluoride and organo-substituted silicon fluorides. Disubstituted compounds are obtained by the reaction of dilithium hexamethylcyclotrisilazane with silicon fluorides or by the reaction of lithium hexamethylcyclotrisilazane with silicon fluorides at higher temperature. Cyclosilazanes with bulky ligands react with butyllithium with elimination of butane as a first step and then react further with a silicon fluoride compound, with LiF-elimination, to give a mixed substituted cyclosilazane. Ring coupling through a silicon bridge is achieved by the reaction of a fluorosilyl-substituted cyclotrisilazane with lithium hexamethylcyclotrisilazane. The mass,¹H and¹⁹F NMR spectra of the compounds are reported.     

Synthesis of Poly(arylene vinylene)s with Different End Groups by Combining Acyclic Diene Metathesis Polymerization with Wittig‐type Couplings

A series of end‐functionalized poly(9,9′‐di‐n ‐octylfluorene vinylene)s (EF‐PFVs) with different end groups were obtained by 1) synthesizing EF‐PFV with vinyl end groups by acyclic diene metathesis (ADMET) polymerization with a molybdenum catalyst and termination with an aldehyde and 2) subsequent olefin metathesis of the vinyl group with the molybdenum catalyst followed by Wittig‐type coupling with another aldehyde. The exclusive formation of EF‐PFVs containing a vinyl end group by the ADMET polymerization was confirmed by grafting PEG, and by the synthesis of amphiphilic triblock copolymers by combining atom transfer radical polymerization from the PFV chain end with PEG grafting through a click reaction. Various EF‐PFVs with different end groups, such as C₆F₅, pyridyl, ferrocenyl, and terthiophene, have thus been prepared. Their fluorescence spectra (e.g., intensities, emission wavelengths) were influenced by the end groups and the length of the conjugation.     

河豚鱼、鳗鱼和烤鳗中角黄素残留的超高效液相色谱法测定和超高效液相色谱-串联质谱法确证

建立了河豚鱼、鳗鱼和烤鳗中角黄素残留的超高效液相色谱测定方法和超高效液相色谱-串联质谱确证方法。样品用抗氧化剂焦性没食子酸保护,乙腈均质提取,正己烷液-液分配净化,超高效液相色谱-紫外检测器测定,外标法定量,超高效液相色谱-串联质谱法确证。测定方法采用BEHC18色谱柱(50 mm×2.1 mm,i.d.1.7μm),流动相为V(0.1%的甲酸)∶V(乙腈)=3∶97,检测波长470 nm。实验结果表明,角黄素在0.05~2.0 mg/L范围内线性关系良好(r=0.9999),在空白样品中,添加低、中、高3个浓度水平(0.05,0.1,1.0 mg/kg),角黄素的回收率均在82.52%~96.96%之间,相对标准偏差为6.9%~15%。方法的检出限(LOD)为0.02 mg/kg,定量限(LOQ)为0.05 mg/kg。串联质谱确证方法采用电喷雾(ESI)离子源,在正离子模式下以多反应监测(MRM)扫描方式检测,定性离子对565.5/203.2和565.5/133.1,定量离子对565.5/203.2。     

基团转移活性聚合物的接枝共聚

以阴离子聚合法合成的窄分布聚苯乙烯（ＮＤＰＳ）进行氯甲基化后,再与由基团转移聚合法合成的活性聚甲基丙烯酸甲酯（ＰＭＭＡ）进行大分子反应,得到了主链为聚苯乙烯,支链为聚甲基丙烯酸甲酯的接枝共聚物（ＰＳｔｇＰＭＭＡ）;探讨了聚合物的合成条件,ＧＰＣ测试结果表明,得到的接枝共聚物的分子量和设计分子量相近且主链和支链分子量均可较好的控制．利用扫描电镜、核磁和红外技术对ＰＳｔｇＰＭＭＡ的形态、结构进行了表征．     

Highly efficient synthesis of linear pyrrole oligomers by twofold Heck reactions

The twofold Heck reaction of the vinylpyrroles 3a and 3b with the iodobenzenes 4a-c led to the linear pyrrole oligomers 5, 6, and 7. The synthesis of both symmetrical and unsymmetrical oligomers, such as 10a and 10b, was also accomplished by a Heck reaction of 8 and 9 and by a Heck reaction of 3a and 11 followed by a Wittig reaction and a second Heck reaction with 8. The pentacyclic oligomers 14 and 19 were prepared by a twofold Heck reaction of 13 with 4 and by a twofold Heck reaction of 15 with 16 followed by a Wittig reaction and a twofold Heck reaction with 8.     

Complexometric determination of citric acid with copper

A method is presented in which citrate is determined by complexation with excess of copper(II), followed by back-titration with EDTA. Small amounts of citrate can be determined by this method in the presence of large amounts of most organic acids present in natural products. Interfering reductants are removed by treatment with permanganate, amino-acids with nitrous acid, and metal ions with a cation-exchange resin. The indicator used for end-point detection is Szechromotrope, 4,4'-sulphonyl-bis(azobenzene) dichromotropic acid.     

Polybutadiene Modification: Reactions of Halogen-Containing Polybutadienes with Organolithium Compounds

Polybutadiene (PB) can be easily halogenated by reaction with iodine chloride or bromine in tetrahydrofuran. The resulting glassy polymers were reacted with n-butyllithium, sec-butyl-lithium, and polystyryllithium in THF. Iodochlorinated PB gave a polybutadiene with a different cis/trans ratio with n-BuLi. The reformation of PB was accompanied by partial crosslinking. The reaction probably involved a halogen-metal exchange followed by intra- and intermolecular elimination of Li halide. With brominated PB, both coupling and elimination took place. With sec-BuLi, an allylic iodine derivative was obtained from iodochlorinated PB, probably by dehydrochlorination. The iodinated intermediate can easily undergo a coupling reaction with further sec-BuLi. Both iodochlorinated and brominated polybutadienes gave graft copolymers by reaction with polystyryllithium in THF. Grafting was always accompanied by gel formation.     

稀土奥贝蠕铁制取工艺及其性能的研究

稀土奥贝蠕铁可用含稀土的蠕化剂及等温淬火工艺稳定地制取,藉助高温扫描电子显微镜,观察并研究了稀土蠕铁奥氏体化过程及稀土奥贝蠕铁随温度升高时组织的变化。用带有加热装置的万能材料试验等土奥贝蠕铁的各种性能进行了系统测定了如抗拉强度、延伸率、冲吉韧性、热膨胀系数及伸长百分率,结果表明,稀土奥贝蠕铁在室温和高温下均有良好的性能。     

MPW1K Performs Much Better than B3LYP in DFT Calculations on Reactions that Proceed by Proton-Coupled Electron Transfer (PCET)

DFT calculations have been performed with the B3LYP and MPW1K functional on the hydrogen atom abstraction reactions of ethenoxyl with ethenol and of phenoxyl with both phenol and alpha-naphthol. Comparison with the results of G3 calculations shows that B3LYP seriously underestimates the barrier heights for the reaction of ethenoxyl with ethenol by both proton-coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms. The MPW1K functional also underestimates the barrier heights, but by much less than B3LYP. Similarly, comparison with the results of experiments on the reaction of phenoxyl radical with alpha-naphthol indicates that the barrier height for the preferred PCET mechanism is calculated more accurately by MPW1K than by B3LYP. These findings indicate that the MPW1K functional is much better suited than B3LYP for calculations on hydrogen abstraction reactions by both HAT and PCET mechanisms.     

Direct TLC Resolution of the Enantiomers of Three β-Blockers by Ligand Exchange with Cu(II)–l-Amino Acid Complex, Using Four Different Approaches

TLC experiments have been performed to resolve the enantiomers of three β-blockers by complexation chiral TLC with Cu(II) cation and five l amino acids. Loading was carried out by using the Cu(II)–l amino acid complex as chiral mobile phase additive with untreated silica gel plates; by mixing the Cu complex with silica gel before preparing the TLC plates; by ascending development of untreated plates with solutions of the Cu complex; and by using a solution of Cu(II) acetate as mobile phase additive for plates prepared by mixing the l amino acid with silica gel. Spots were located by use of iodine vapour.     

Photo-Degradable Protein-Polymer Hybrid Shells for Caging Living Cells

There is growing demand for the precise remote control of cellular functions in various fields. Herein, a method for caging mammalian cells by coating with photodegradable protein-polymer hybrid shells to photo-control their functions without genetic engineering is reported. A layer-by-layer assembly of photocleavable synthetic materials through biotin-streptavidin (SA) binding was employed for cell coating. The cell surfaces were first biotinylated with photocleavable biotinylated poly(ethylene glycol)(PEG)-lipid and then coated by repeatedly layering SA and micelles of the PEG-lipid and photocleavable biotinylated four-arm PEG. The cell extension and adhesion were suppressed with the shells and then triggered with the degradation of the shells by light exposure. Macrophage phagocytosis was also stopped by caging with the shells and restarted by light-guided uncaging. This study provides the first proof of principle that cellular functions can be remotely controlled by steric hinderance of cell surfaces with photodegradable materials.     

Determination of isoniazid in drugs

A titrimetric method is described for the determination of isoniazid in pharmaceutical preparations. Samples are treated with an excess of iodine monochloride, and the iodine produced is titrated with iodine trichloride to an Andrews end-point. p-Aminosalicylic acid undergoes only nuclear iodination and does not interfere. Mixtures of isoniazid with vitamin C or methionine are analysed by first titrating both compounds by the Andrews method and then determining either vitamin C alone by titration with iodine monochloride or methionine by a second Andrews titration after destruction of isoniazid with nitrous acid. In both cases, isoniazid is obtained by difference. A mixture of isoniazid, methionine and vitamin C can also be analysed.     

Reactions of pyranylidenemethylpyrylium salts with ammonia and amines

Pyranylidenemethylpyrylium salts (1) react with ammonia to give pyranylidenepyridines as a result of the replacement of one of the oxygen atoms of 1 by nitrogen. Aliphatic primary amines react with 1 by replacing both of the oxygen atoms by nitrogens. Aniline and 1 give the monoreplacement product. Pyranylidenemethylthiopyrylium salts have only the oxygen atom replaced by reaction with primary aliphatic amines.