Chikayoshi Nagata

Molecular Orbital Theory of Orientation in Aromatic, Heteroaromatic, and Other Conjugated Molecules

As to the LCAO MO treatment of the orientation problem in chemical reactions of π‐electron systems, the frontier electron concept which has been previously introduced by the authors for explaining the reactivities in aromatic hydrocarbons is subjected to an extension in the sense that the frontier orbitals are specified according to the type of reaction. Thus, fundamental postulates relating to the reactivities of π‐electron systems are set up, which are believed to include general principles involved in the mechanism of both substitution and addition of electrophilic, nucleophilic, or radical type. On the basis of these postulates it is possible to predict the position of attack in conjugated molecules in all the three types of substitution as well as addition in a consistent manner. There is a nearly perfect agreement between the theoretical conclusions and experimental results hitherto reported.

Cigarette smoke induces DNA single-strand breaks in human cells

Epidemiological evidence suggests that smoking is a major cause of human lung cancer1,2. However, the mechanism by which cigarette smoke induces the cancer remains obscure, although in tobacco Carcinogenesis, promotion and/or co-carcinogenesis may have crucial roles. The epidemiological data show that if an individual stops smoking, the risk of his contracting lung cancer increases no further. Moreover, laboratory experiments show that cigarette smoke condensate (CSC) exhibits co-carcinogenic and promoting activities in tumour production and malignant transformation3–5. Clastogenic action is thought to be intimately involved in tumour promotion6–8, and it is therefore interesting that visible chromosome changes such as chromosome aberrations and sister chromatid exchanges are known to be caused by cigarette smoke9–11. However, there has been no previous direct demonstration that cigarette smoke can cause single-strand breaks (SSB) in DNA. Here we report that cigarette smoke induces considerable numbers of DNA SSB in cultured human cells, and that such strand breaks may be ascribed to active oxygen generated from cigarette smoke.

MO‐Theoretical Approach to the Mechanism of Charge Transfer in the Process of Aromatic Substitutions

An MO‐theoretical investigation on the mechanism of aromatic substitution is made. Supposing that the approaching reagent and the atom to be replaced can be treated as an atom (pseudoatom) which has a π‐type orbital in the course of reaction, an important role of hyperconjugation taking place between the pseudoatom and the aromatic compound is remarked. Since the electron density at the pseudoatom relates to the amount of charge transfer through this hyperconjugation and varies as the reaction proceeds, the proceeding of the reaction can be measured by this electron density. Then, the electron density is expressed, in the form of a contour diagram, in terms of the Coulomb integral of the pseudoatom and the resonance integral between the pseudoatom and carbon atom to be attacked. Thus, a reaction path can be represented by a locus plotted on this diagram. The discriminating property of frontier orbitals can be observed in this diagram. It has been confirmed that an electrophilic, or a nucleophilic, substitution takes place only when a certain condition is satisfied with respect to the energy of the reagent. By determining the transition state which corresponds to the end point of the locus, several reactivity indices, i.e., frontier electron density, superdelocalizability, its one‐term approximation and a generalized reactivity index are derived from the hyperconjugation energy at the transition state, which is also available as a generalized reactivity index. Correlation between these and the existing indices is examined.

Interrelations of Quantum‐Mechanical Quantities Concerning Chemical Reactivity of Conjugated Molecules

It is attempted here to disclose the interrelations underlying the parallelism found in several quantum‐mechanical methods previously proposed to explain chemical reactivity in conjugated molecules. This is carried out mathematically in alternant hydrocarbons and hetero‐alternant molecules mainly by the use of Coulsons integral formulas. In an alternant hydrocarbon, provided a condition is satisfied between minors of the secular determinant, the orders of reactivity of each position predicted by the self‐polarizability, free valence, superdelocalizability, Whelands localization energy, and Dewars approximate localization energy by NBMO are shown to be in complete agreement with one another. The relation of the frontier electron density and superdelocalizability is discussed. It is also demonstrated that a nonperturbation treatment for the so‐called static method leads us to the same conclusion as the perturbation treatment. The parallelism of various quantities is discussed in their relation to the eff...

A molecular orbital study on the enzymic reaction mechanism of α-chymotrypsm

Abstract On the basis of the three-dimensional structure of the active site of α-chymotrypsin determined by X-ray diffraction analysis, we calculated a total energy and delocalization energy by using a molecular orbital method including all valence electrons, i.e. σ- and π-electrons. The calculated potential curve for a hydrolysis by a-chymotrypsin reproduced the experimental curve well, and the relative magnitudes of all steps in the reaction path explain the experimentally obtained activation energies satisfactorily. The validity of the “charge relay system” proposed by Blow and co-workers was investigated from the quantum-chemical point of view, and the possible importance of this structure for the acceleration of the hydrolysis through a proton transfer within the active site was pointed out. Delocalization energy was proved to play an important role in lowering the activation energy, and the effect of “orbital steering” suggested by Koshland and co-workers was also shown to be of importance for the catalytic reaction of α-chymotrypsin.

A molecular orbital study of stability and the conformation of double-stranded DNA-like polymers

Abstract The stacking and hydrogen bonding energies between bases in the B form of DNA were calculated by a perturbation method using the wave functions by the CNDO and the P-P-P methods. The exchange energies were calculated by using the corresponding orbitals. The magnitudes of the sums of the average stacking and hydrogen bonding energies per base pair of double-stranded DNA-like polymers are in good parallel with the melting temperatures of the polymers. The polymers containing I-C pairs are exceptions to this relation. Intrastrand stacking bases have the potential minimum at the distances of 2·8–3·7 A. The minimum of stacking energy of double-stranded polymer for rotation of base pair around the helix axis exists near 36°. The deviation of the potential minimum from 36° seems to parallel the feature of the X-ray diffraction pattern of the polymer.

An ab initio MO study on the disulfide bond: properties concerning the characteristic S-S dihedral angle

The characteristics of disulfide groups concerning the S-S dihedral angle are represented by ab initio SCF calculations using the split-valence 6-31G(*) basis set. It is shown that the hyperconjugation between the S-H bond and the electron pair on the other sulfur plays an important role in determining the characteristic S-S dihedral angle. The S 3d orbitals do not participate in such characteristics. The nature of the S-S bond is compared with that of the O-O bond. The S-S bond length varies largely depending on the S-S dihedral angle. This is related to the frequency-conformation correlation of the disulfide group.

Novel Perturbation Theory in Simple LCAO Treatment of Conjugated Molecules—Method of Perturbed Secular Determinant

A new method of perturbation theory is developed in the simple LCAO MO treatment of conjugated molecules. Several useful equations are derived, giving orbital energy, electron density, and bond order of the perturbed system.

Quantum-mechanical study on the photodimerization of aromatic molecules

Abstract Distinct parallelism is found between the quantum-mechanical index, the π delocalization energy and the degrees of dimer-forming ability of thymine, uracil and other aromatic compounds. It is surprising that the π delocalization energies for thymine and uracil are larger than those of well-known photodimer-forming compounds such as anthracene and acenaphthacene. The possible structures of thymine dimer isomers in vitro and in vivo , are postulated from considerations of, for example, the π delocalization energy and steric properties. Biological inactivation by photo-irradiation is discussed in relation to the energy liberation due to the thymine dimer formation.

Electronic Structure and Nicotine-like Stimulant Activity in Choline Phenyl Ethers

Frontier electron density at the ether oxygen position and superdelocalizability at the ortho position show good parallelism with biological activity—that is, the stimulant activity of phenyl ether choline molecules. The mechanism of the biological action is discussed in connection with this finding.