Total surface areas of Group IVA organometallic compounds: Predictors of toxicity to algae and bacteria

There is a high correlation between molecular surface area (TSA) of triorganotin and triorganolead compounds and their toxicity towards a bacterium (Escherichia coli) and an alga (Selenastrum capricornutum). Parallel attempts to correlate other Group IVA organometals incorporating silicon or germanium were unsuccessful. It was further demonstrated, however, that a high correlation was obtainable between certain series of compounds with the same organic substituent but different metal centers involving all Group IVA elements. In both instances, the inability to obtain a quantitative structure-activity relationship (QSAR) for all systems studied appears to be a function of the solubility of the compounds. While organotin TSA values have been found to correlate well with their toxicities toward various organisms, this study clearly suggests that this type of QSAR can be readily extended to include other organometal systems, provided that there is no solubility problem and the toxicity is a function of the hydrophobicity of the organometal compounds.     

Modeling of drug molecule orientation within a receptor cavity in the BiS algorithm framework

The BiS algorithm is suggested for modeling the drug molecule orientation within a receptor cavity. It is based on the assumption of complementarity of the field created by biologically active compounds and the field of the responsive receptor. The comparison of predicted orientations of various biologically active compounds on the relevant receptors with the data of X-ray structural studies (Protein Data Bank) reveals that the results obtained with this approach surpasses those reported in the literature. The suggested technique made it possible to elucidate the details of the action mechanism of DNA antimetabolites, dihydrofolate reductase inhibitors. The dependence of the activity on the structural parameters of “ligand-receptor” complexes is determined.     

3-乙氧基-6-取代苯氧基哒嗪除草活性的相关性研究

在分子拓扑理论的基础上,构建了新的结构信息价连接性指数mχY和取代基染色指数I,并用它们研究了3 乙氧基 6 取代苯氧基哒嗪的除草活性pI50与其结构之间的定量关系,给出了相关方程,相关性良好,复相关系数分别为R1=0.9807、R2=0.9926、R3=0.9881,并预测了几个化合物的pI50值,预测值pI50(cal.)与测定值pI50(exp.)相当吻合.新方法计算方便、结果可靠.     

The structure-activity relationship of inhibitors of serotonin uptake and receptor binding

Summary An analysis of five different datasets of inhibitors of serotonin uptake has yielded quantitative structure/ activity relationships (QSARs) which delineate the role of steric and hydrophobic properties essential for inhibition by phenylethylamine-type analogues.     

QSAR modeling with the electrotopological state indices: Corticosteroids

A structure-activity analysis of a series of steroids binding to corticosteroid-binding globulin was made using the electrotopological state index for each atom in the molecule. Two indices were found to correlate well with the binding affinity. The indices encode structural characteristics in the A and the D rings of the steroids in the study. One of the indices was formulated as the difference between two indices in the A ring. The two were not intercorrelated, suggesting that the composite index signals the influence of structure changes in or near the A ring that can be monitored by the composite index. This is a new observation using this structure-activity method. It is suggested that this model makes some contributions towards detection of the pharmacophore.     

Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

Summary Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.     

取代苯酚的定量结构－活性／性质相关性研究

在分子拓扑理论基础上,提出了一个新的价连接性指数~nG=∑(E_i·E_j· E_k...),其中~0G=∑(E_i),~1G=∑(E_i·E_j),并用~0G,~1G研究了取代苯酚（ 含Cl,Br,INH_2,NO_2,COOH,烷基、环烷基、苯基等）的溶解度,辛醇／水分 配系数及对黑曲霉、浮萍、细胞色素P－450、酵母菌等的生物活性,给出了相关方 程。结果表明,新方法计算简单,使用方便,预测值与相应的实验值较好吻合。     

新定义的价连接性指数与有机物理化活性的相关性研究

基于分子中成键原子i的结构特征和所处的化学环境,新定义了原子的价点价δYi,以价连接矩阵为基础构建了一个新的能表征含多重键、杂原子分子结构信息的价连接性指数mωY. mωY对有机化合物异构体具有很强的选择性和区分能力.用0ωY, 1ωY和分子中的含碳数NC研究了有机物的一系列理化活性,其相关性良好,并发现不同的性质,0ωY, 1ωY和NC所起的作用程度是有所不同的.新模型物理意义明确,计算简便,对不同类型有机物的不同理化活性具有良好的估算和预测能力,计算值与实验值的吻合程度均优于相应文献的结果.     

Three-dimensional structural features and the toxicity of aminobenzenes and phenols

There are many organic pollutants in the environment, such as polychlorinated biphenyl, polycyclic aromatic hydrocarbons, dichlorodiphenyl-trichloroethane (DDT), and polychlorinated naphthalene. These organic pollutants are persistent,liposoluble and easily cumulated in organism; consequently, the potential toxicity will be high. Risk assessment of industrial chemicals is currently carried out using scanty experimental data, because many of these chemicals have very little or no test data. S…