Researches of organic chemistry are now in a great revolution, which is aroused by the followings ; (1) popularization of AI systems for organic chemistry such as synthetic design systems and structure analysis ones, (2) laboratory automation, and (3) changes in social consciousness. This article discusses the contents of the present revolution as well as the directions of the future one.

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The Committee on the Future Trends of Chemical Research of the Chemical Society of Japan recently published the final report, which contained a Chapter titled “The Role of Computers in Chemistry”. In this Chapter are described the following predictions : “While the role of computers in chemistry will undoubtedly continue to become more and more important, one of the most promising research fields that are considered to be crucial for the future of chemistry is the theoretical calculations and their applications with the aid of computers.” Theoretical chemical methods that fit particularly well with computer are the molecular orbital calculation and the molecular mechanics calculation. The former is described in detail elsewhere in this Symposium on Paper. For the latter, which may be best called as a computerized molecular modelling, the technical aspects including specific applications also are described elsewhere in this Symposium. This article is a general introduction to those articles and concentrats on the basic aspects and the prospects.

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Examples of the application of molecular mechanics calculation in organic synthesis have been reviewed. Allinger's MM2 program has been used successfully in the the analysis and designing of synthetic reactions as well as total synthesis of complex molecules. A recent approach to the theoretical analysis of the reactions involves the modeling of the transition state by combining the accuracy of the ab initio calculation and the facility of MM2 calculation. This new approach has proven to be a very powerful method of analyzing the reactivities of molecules as complex as the one we encounter in modern organic syntheses.

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Recent theoretical studies on reactions of organotransition metal complexes will be reviewed, in which the structures of transition states as well as reactants and products have been optimized with the ab initio molecular orbital energy gradient method. Those studies have covered the elementary organometallic reactions such as oxidative addition/reductive elimination, olefin insertion/β-hydrogen elimination, carbonyl insertion, thermolysis of ketene complex, isomerization of metallacycle to an alkylidene-olefin complex and methylidene migratory insertion into an M-H bond. In addition, as a combination of a series of elementary organometallic reactions, the potential energy profile of a full catalytic cycle of olefin hydrogenation by the Wilkinson catalyst has been obtained.

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In this article, current state of the art in computer aided design of catalysts is given. It is shown that entire catalyst design is composed of various kinds of unit designs, and then, for each of those. the applicability of computer aided design approach is discussed. The available design tools such as information retrieval systems, catalyst design specific database and reaction design systems are described. Among these it is pointed out that an artificial intelligence approach originally applied to this field by the authors is of bright future. This is because it can use human heuristic expertise which plays a very important role in the process of catalyst design.

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An index which corresponds to the charge transfer interaction is presented to study the correlation of molecular orbital (MO) distributions. The MO distribution correlation (MODIC) index was applied to Diels-Alder reaction systems (1-methoxy-1, 3-butadiene-acrolein system, cyclopentadiene-maleic acid anhydride system. 2-methoxy-5, 6-dimethylene-1, 3-cyclohexadiene-ethoxyethylene system, 1, 3-pentadiene-methyl acrylate system, and 6, 6-dimethylfulvene-isobenzofuran system). In these Diels-Alder reaction systems, the positions of reaction centers and the orientations of substitutional groups were predicted by the index in consistent with the experimental facts. The present methodology wolud be applicable to other reaction systems, and also to biological systems.

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It is well known that chemical structure diagram or three-dimensional structure of a compound molecule involves much information related to biological activity, reactivity, or various physicochemical properties on itself. It is a very important thing in a wide range of chemical research to compare the chemical compounds on the basis of such structural information. Especially, in the area of structure-activity studies, to investigate structural feature such as functional groups or substructural fragments, common to a group of chemical compounds exhibiting a particular biological activity often provides us with very useful and objective information which may be resulted in hypothetical pharmacophore.
In this article, a couple of approaches for the automated recognition of common structural patterns among drug molecules will be described. One is related to the maximal common substructure search which can be used to find some topological pharmacophore, and the other one is for the common geometrical pattern search in which three-dimensional geometry of molecules are taken account. The latter approach may be used to identify a certain topographical or three-dimensional pharmacophore. The basic algorithms and related software systems will be summarized with some illustrative examples.

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The function of a bioactive peptide is often dictated by the bioactive conformation that fits into its receptor. Conformational energy calculations (Molecular Mechanics) as well as various experimental methods have been used for this purpose. On the other hand, recent molecular dynamics simulations of proteins have provided us the new dynamic picture of protein structures. These theoretical methods are thought to play an important role in elucidating the receptor mediated events of bioactive peptides and in the drug design based on their conformations.
The objectives of this review are (1) to provide an introduction to the field of conformational energy calculations and molecular dynamics for peptides; (2) to explain how we can find the bioactive conformation by using conformational energy calculations; and (3) to describe the application of the above methods for defining the bioactive conformation of an opiate peptide, Morphiceptin, as one example.

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This article describes the structure-activity relationships of (i) herbicidal N-benzylphenylacetamides, (ii) herbicidal N-chloroacetyl-N-phenylglycinates, (iii) herbicidal N-phenylureas, (iv) herbicidal N-benzylacylamides, (v) herbicidal and fungicidal N-benzylacylamides, and (vi) fungicidal N-phenylimides analyzed quantitatively with substituent parameters and regression techniques. The activity-activity correlations between activities against different species of weeds and fungi are examined on the basis of structure-activity relationships. The application for the design of new agrochemicals with wide-spectrum and/or selectivity is discussed.

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Computer assisted (aided) molecular modeling is becoming a powerful tool for chemists. This trends owes much to increasing computer powers, developments of three-dimensional computer graphics hardwares and developments of computational theory and many good softwares. Among various computational methods, molecular mechanics calculation is popularly used to predict stable structure and/or stable conformation of molecules and to estimate energetics of molecules. Structures of many biologically important small and macro-molecules have been elucidated by X-ray crystallography. Docking simulation study is useful for designing new drugs when the structure of the target protein is known. Along with its merits, current limitations and future of computer assisted molecular modeling are also discussed.

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It is becoming commonplace for organic chemists to have their own microcomputers. In this article, softwares for such users to carry out two or three dimentional input to a computer, graphic display of molecular structures, and molecular orbital calculations are reviewed (129 references).

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