Mototsugu Yoshida

Quantitative structure-Activity studies of pyrethroids: 28. Type differentiation of action-potential changes in crayfish giant axons caused by substituted benzyl chrysanthemates and pyrethrates

Abstract The neurophysiological actions of variously substituted benzyl (1R)-trans -chrysanthemates and (1R)-trans-(E) -pyrethrates on the membrane potential of crayfish giant axons were observed by use of an intracellular microelectrode. The compounds were classified into three types according to their effects: deceleration of the falling phase of the action potential (type A), elevation of the depolarizing afterpotential (type B), and a combination of these effects (type C). The effects of substituents on the benzyl-benzene ring of the alcohol moiety on the type differentiation of actionpotential changes were examined by such statistical procedures as linear discriminant and logistic regression analyses with physicochemical substituent parameters. Logistic regression analysis was especially efficient in type classification. The most important substituent factors governing the type differentiation were steric bulk and electronic property. With increases in the bulkiness of substituents in terms of the van der Waals volume, the compound tended to change in its effects in the order of type A, type C, and type B. The greater the electron-withdrawing property, the greater was the tendency of compounds to be classified as type B.

Application of the stepwise clustering method for efficient drawing of biopolymer structures

The reduction of drawing time is desirable in writing a complex molecular structure by use of a plotter. The stepwise clustering method is applied to find efficient drawing paths for six structures of protein and DNA molecules. All the optimization ratios of path lengths exceed 50%, while the necessary CPU times are of the order of 0.1 second. These results show the effectiveness of the method for molecular graphics. A summary of the algorithm and other possible applications are also discussed.

Phase Transition Study of Liquid Crystalline Polymers by MD Simulations

Molecular dynamics simulations are studied using mesogenic core model for liquid crystalline polymer. A temperature dependence of L/D ratio of the mesogen is analyzed. Simulations for typical liquid crystalline molecule TBBA (telephthal-bis-4-n-buthylaniline) are carried out under the constant temperature(at 100K intervals in the region 100–1000K). Time-averaged L/D calculated from the simulation data becomes smaller as temperature becomes higher. A deflection point exists in the region 500K-600K. Standard deviation of L/D changes drastically in the region 520K-540K. This temperature region corresponds to experimental isotropic-nematic transition temperature.

Application of the new chemometric system SPECTRE to quantitative structure-activity relationship (QSAR) in agricultural drug design

A new modeling algorithm has been developed which analyzes experimental data by computing a statistical predictive model. The algorithm is an evolution of the PLS (Partial Least Squares) regression method, in which insignificant variables among the initial variables can be eliminated automatically before expressing the relationship in the data. In this study, a new version of the chemometric system SPECTRE, employing this technique, has been applied to quantitative structure-activity relationship (QSAR) analysis of fungicidal 1-acyl-3-(3,5-dichlorophenyl)-2,4-imidazolidinediones against Botrytis cinerea and Alternaria kikuchiana. The new modeler of SPECTRE automatically derived significant models without any human intervention in the decision process.

APPLICATIONS OF THE COMPUTER AIDED CHEMISTRY SYSTEM ACACS IN AGRICULTURAL CHEMICAL RESEARCH

We developed an interactive computer system for molecular design called ACACS through the joint cooperation with Sumitomo Pharmaceuticals Co., Ltd. and NEC Corporation. In the ACACS system, computer graphics is used to examine similarities in three-dimensional structure among compounds. We have used this system in research on various agrochemicals such as pyrethroid insecticides. We investigated similarities in molecular shape among several alcohol moieties of various ester type pyrethroids, and between ester and ether type pyrethroids, based on conformational analyses with molecular orbital methods. Furthermore, we presented a candidate for the active conformer of an ester type pyrethroid, esfenvalerate, based on conformational analyses and shape comparisons with low-activity pyrethroids.

THE AUTOMATION OF ORGANIC SYNTHESIS DESIGN: A BEGINNING

An introduction is given to the program SYNSUP-MB, a long term project of the Sumitomo Chemical Company. At present, it has a little over 2000 reactions. The program proposes synthetic routes without interacting with a chemist during its execution. The routes are usually reasonable. The program has thus far been limited to molecules with only a few stereocenters. Routes for the total synthesis of large and complicated molecules, e.g. steroids and tetracycline antibiotics, have thus far not been proposed by the program. Most of the knowledge in typical compendia of synthetic organic reactions (1,2,3) is still missing from the program.