Guest—host complexes of spin-labeled indoles with cyclodextrins in the solid phase: an esr study

Inclusion complexes of spin-labeled pyrrolidine-(1) and piperidine-containing (2) indole derivatives with β-cyclodextrin and γ-cyclodextrin (CD) were prepared in the solid phase and studied by ESR in a wide temperature interval. For all complexes and free spin probes in solvents of different polarity, local environment polarities of the NO group of the guest molecules were determined from the outer extrema separations in the ESR spectra measured at 77 K. From analysis of the Saturation Transfer (ST) ESR spectra and temperature dependences of linear ESR spectra of the complexes it follows that both guest molecules in γ-CD undergo rapid librations. The libration amplitude of the p-orbit axis of the NO group in molecule 2 increases with temperature and reaches about 16° at 333 K. The ESR lineshape of the β-CD complexes depends on the spin probe/β-CD molar ratio (ρ) even at ρ < 0.01. Lineshape analysis of the spectra recorded at different ρ showed that they consist of two components, one of them corresponding to strong spin-spin interaction between guest molecules and the other corresponding to almost absence of this interaction. The spectral components can be attributed to microphases of the complexes and to isolated complexes in the β-CD matrix, respectively. Simulation of the ST ESR and linear ESR spectra of the magnetically diluted complexes showed that the guest motion inside the CD cavity is better described by rotational jumps rather than Brownian diffusion in an orientation potential. In the temperature range 238—333 K, the rotational frequencies of 1 and 2 are in intervals 1.8·10⁷−6·10⁷ s⁻¹ and 4·10⁷⁻¹.3·10⁸ s⁻¹, respectively. The rotation occurs over the whole solid angle. Significant differences in the character of molecular dynamics in the γ-CD and β-CD complexes can be explained by different stoichiometry, namely, 1: 1 for the former and 2: 1 for the latter and by different orientation of guest molecules in the complexes. In both cyclodextrins the rotational mobility of molecules 2 is higher than that of 1 owing to intramolecular conformational transitions in the piperidine ring of 2 and steric hindrances produced by the methyl group in 1. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 233—241, February, 2006.     

Random walk in random environment: A counterexample without potential

We describe a family of random walks in random environment which have exponentially decaying correlations, nearest neighbor transition probabilities which are bounded away from 0, and are subdiffusive in any dimensiond<. The random environments have no potential ind>1.     

Effectiveness of graph-based and fingerprint-based similarity measures for virtual screening of 2D chemical structure databases

This paper reports an evaluation of both graph-based and fingerprint-based measures of structural similarity, when used for virtual screening of sets of 2D molecules drawn from the MDDR and ID Alert databases. The graph-based measures employ a new maximum common edge subgraph isomorphism algorithm, called RASCAL, with several similarity coefficients described previously for quantifying the similarity between pairs of graphs. The effectiveness of these graph-based searches is compared with that resulting from similarity searches using BCI, Daylight and Unity 2D fingerprints. Our results suggest that graph-based approaches provide an effective complement to existing fingerprint-based approaches to virtual screening.     

基于分子对接的苯丙素甙（PPGs）类化合物的虚拟筛选和合理设计

采用虚拟化合物生成法对抗肿瘤的苯丙素甙(PPGs)类化合物进行了配体受体对 接研究。以三种不同的骨架结构为基础分别生成了五十个虚拟苯丙素甙(PPGs)类化 合物，并将它们与端粒DNA受体进行分子对接，分析已知结构的对接结果，通过虚 拟筛选的方法得到了一批与受体相互作用能较高并且复合物能量较低的新的有潜力 的活性化合物。该方法可以弥补分子对接研究中，只能计算药物与受体的相互作用 ，无法有效设计新化合物的不足。这种方法在基于结构的药物分子设计中具有重要 的意义。     

Tomocomd-Cardd, a novel approach for computer-aided ‘ rational’ drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds

Summary In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silicoscreening and several compounds from the Merck Index, Negwers handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100) with model predictions. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.     

Fast 3D molecular superposition and similarity search in databases of flexible molecules

We present a new method (fFLASH) for the virtual screening of compound databases that is based on explicit three-dimensional molecular superpositions. fFLASH takes the torsional flexibility of the database molecules fully into account, and can deal with an arbitrary number of conformation-dependent molecular features. The method utilizes a fragmentation-reassembly approach which allows for an efficient sampling of the conformational space. A fast clique-based pattern matching algorithm generates alignments of pairs of adjacent molecular fragments on the rigid query molecule that are subsequently reassembled to complete database molecules. Using conventional molecular features (hydrogen bond donors and acceptors, charges, and hydrophobic groups) we show that fFLASH is able to rapidly produce accurate alignments of medium-sized drug-like molecules. Experiments with a test database containing a diverse set of 1780 drug-like molecules (including all conformers) have shown that average query processing times of the order of 0.1 seconds per molecule can be achieved on a PC.     

偶合化学发光法测定环境水样中的痕量亚硝酸根

将亚硝酸盐在酸性条件下氧化亚铁氰化钾为铁氰化钾的反应 ,和尿酸 铁氰化钾 鲁米诺化学发光反应偶合一起 ,建立了一种间接测定亚硝酸根离子的新方法。讨论了酸度、反应物浓度、干扰离子等因素的影响。方法的检出限为5 .0× 1 0 - 1 1 g/mL ,对环境水样样品进行了平行测定 (n =1 1 ) ,其相对标准偏差为1 .8%～ 3 2 % ,线性范围为 1 .0× 1 0 - 9g/mL～ 1 .0× 1 0 - 5g/mL ,回收率为 94.3%～ 1 0 5 3%。     

Transient solution for a finite capacity M/G a,b /1 queueing system with vacations to the server

In this paper we consider a single server queueing system with Poisson input, general service and a waiting room that allows only a maximum of b customers to wait at any time. A minimum of a customers are required to start a service and the server goes for a vacation whenever he finds less than a customers in the waiting room after a service. If the server returns from a vacation to find less than a customers waiting, he begins another vacation immediately. Using the theory of regenerative processes we derive expressions for the time dependent system size probabilities at arbitrary epochs.     

城市环境近地表大气尘研究的意义及进展

近地表大气尘采集于人的平均呼吸高度,是较长时间累积的大气颗粒物和地表扬尘的混合物,通过化学成分、矿物组成、粒度分析,可直接获取对人体健康的影响因素,是小区域及城市环境元素迁移转化研究的重要介质,它补充了大气污染0～5 m高度梯度上的研究,对城市环境的治理、城市建设的规划和元素在城市生态环境中迁移转化机理的研究有着十分重要的意义。     

基于虚拟开车环境的自闭症儿童脑电样本熵

自闭症谱系障碍是一种涉及感觉、情感、记忆、语言、智力、动作等认知功能和执行功能障碍的精神疾病. 本文从神经工效学角度出发, 用虚拟开车环境作为复杂多任务激励源将大脑系统与人体动作控制等有机地结合起来, 通过对脑电信号的滑动平均样本熵分析来探索自闭症儿童在虚拟开车环境中的脑活动特征. 研究发现不论是休息状态还是开车状态, 自闭症患者的滑动平均样本熵总体上低于健康者, 尤其在前额叶、颞叶、顶叶和枕叶功能区, 表明自闭症儿童的行为适应性较低. 不过, 自闭症患者的开车状态与健康受试者的休息状态比较接近, 表明虚拟开车环境或许有助于自闭症患者的干预治疗. 此外, 自闭症患者在颞叶区呈现显著性右半球优势性. 本研究为进一步深入开展自闭症疾病的机理研究及其诊断、评估和干预等研究提供一种新的研究思路.