After briefly reviewing the historical progress of chemical database, The Chemical Factual Database Network promoted by The Science and Technology Agency of Japan is introduced. Within it, central chemical substance dictionary and thermophysical and mass spectral database systems developed by The Japan Information Center of Science and Technology are minutely explained. The most features of the chemical dictionary are its stereochemical structure treatment and automatic construction of the structures from their nomenclatures.
Examples of the application of Molecular Mechanics (MM2) calculation in natural product syntheses using macrocyclic stereocontrolled reactions are presented. MM2 calculations and abinitio MM2 calculations have been used in predictions (or analyses) of the stereoselectivity in macrocyclic reactions such as the transannular Diels-Alder reaction of the 14-membered (E, E, E)-triene, the transannular [2, 3]-Wittig reaction of the 13-membered diallylic ethers, the cyclopropanation and the epoxidation of the 10-membered enones. Moreover molecular designing for the Bergman cyclization of the macrocyclic diynenes based on MM2 calculations are also described.
Chemistry is the field of discussing the behavior of electrons in a molecule. Sixty years ago, the mathematical foundation for predicting the behavior of electrons was given by the quantum mechanics. Now a days, the rapid development of high speed digital computer makes it possible to perform a large scale quantum chemical calculation. Two powerful tools of the quantum chemistry reviewed here are the non-empirical molecular orbital calculation program series: GAUSSIAN and the semi-empirical one: MOPAC. Especially, the treatment of the reaction process in the MOPAC is shown in detail.
Designing molecules has become more and more important in drug development. Computational methods for designing drugs rationally and efficiently are attracting much attention. Methods of Quantitative Structure-Activity Relationships (QSAR) represented by Hansch method seem to be excellent for lead optimization, but not for lead generation. As for lead generation, another computational method based on three-dimensional structures of molecules is expected to be useful. Theoretical calculations on stabilities, physical and chemical properties of molecules, and on molecular interactions with target macromolecules, can give useful informations which enable us to explain structure-activity relationships and to design new active structures. Computer graphics are indispensable tools for performing computer-aided durg design efficiently. We also describe about the basis and application of molecular dynamics calculation.
The use of personal computer in chemical researches is currently excited. New approaches to produce chemical softwares for personal computer have been performed by many chemists and chemical teachers. However, the chemical softwares for a personal computer are scarecely announced in spite of important utility. The author has studied on a software communication of chemistry for a personal computer, and published the annual reporting books ('85, '86, '87, '88) of chemical softwares serially. This paper mentions present states and circulation of personal computer softwares for chemical researches. There are primarily five cases of the softwares, which have been devoted to the problems of molecular science, data processing, chemical graphics, chemical education, and chemical instrumention & chemometrics. The best and most used hardware of personal computer is PC-9801 series by NEC in Japan.
The affinities of eight kinds of carbamate pesticides, MIPC, BPMC, PHC, MTMC, XMC, MPMC, MCC and NAC, with bovine serum albumin, BSA, were examined, and their transport behavior was investigated with BSA as a carrier through a liquid membrane system consisting of a hexane source phase (I), a BSA sulution phase (1/15 phosphate buffer) and a hexane receiving phase (II). All these pesticides showed affinity toward BSA, suggesting involvement of the -NHCOO- group in their binding to BSA. The ratio of the BSA-binding form/free-form was high for MCC and XMC, and relatively lower for the others. An inverse correlation was observed between this ratio and the partition coefficient in a water/n-octanol system. The rate constant of pesticide transport from the haxane phase (I) to the water phase was defined as k1 and that from the water phase to the haxane phase (II) as k2. Positive correlations were observed between k1 and water/hexane partition coefficient, and inverse correlations were found between k2 and the partition coefficient with and without added BSA. It is thus evident that the transport behavior of carbamate pesticides across a water membrane is governed primarily by partition coefficients between water and the hexane phase and that the addition of BSA accelerates the transport of pesticides in the case of lower partition coefficients. Essentially the same was found for steroidhormones in a previous paper. In the case of a lower partition coefficient, the k1 process is a rate-determining step in the transport system, while the rate-determining is changed to the k2 process with increase of the partition coefficient.
The effects of several synergists along with a mixed tocopherols concentrate (m-Toc) on the oxidative deterioration of a high linoleic margarine were compared with those of phenolic antioxidants. The margarine was prepared with blended vegetable oils, mainly safflower oil, whose levels of linoleic and oleic acids were 54.8 and 19.6% to the total fatty acids, respectively. Stability of the margarine against oxidative deterioration was evaluated based on changes in the peroxide value and vitamin A and β-carotene content during storage at 20°C. 1) On oxidation of high linoleic margarine, each tested amino acid except L-proline (Pro) enhanced the effect of m-Toc in the order of L-histidine (His)>L-cystine (Cys)>L-tryptophane (Trp)>glycine. The addition of His or Cys along with m-Toc was the most effective and comparable to that of dibutylhydroxytoluene (BHT) alone. In contrast, L-ascorbyl stearate (AS) and Pro lessened the effect of m-Toc. 2) The effects of synergists along with m-Toc on the stability of vitamin A or β-carotene in the margarine were essentially the same as those on oxidation. The effect of His along with m-Toc, in particular, was superior to that of BHT alone. 3) Amino acids, such as His, Cys or Trp, clearly showed protective effects on the loss of Toc, particularly α-Toc in the margarine, but no effect was observed in AS. BHT and t-butyl-hydroquinone were also somewhat effective.