Quantum chemical study for radical-induced DNA effects and damage.

Differences in molecular interaction between bases (adenine (A), guanine (G), and cytosine (C)) and the methyl (Me)-radical were investigated by perturbation analysis using the quantum chemical method. Part of the source of damage to the DNA was elucidated at the molecular level. In the reaction of each of the saccharide derivatives (dA, dG, and dC) with Me-radical, the reactivity of dG (≈dA) is more than about 10 times larger than that of dC. Therefore, it is expected that the base G (and A) was more than about 10 times than the base C in radical-reactivity of the base. For the reaction of dA and dG with the radical, the C(8) site of the partial purine ring of dA and dG, and the C(5) site of the pyrimidine ring of dC were the main reaction sites for methylation. In the reaction of DNA composed of hydrogen-bonded base pairs G-C and A-T with the radical, the purine ring in the constituent base G reacted preferentially with the radical to yield 8-methyl-guanines.

Synthesis, characterization and preliminary screening of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole and 1-(3-pyridazinyl)-5-arylpyrazole derivatives towards cyclooxygenase inhibition.

In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a-f, 6a-f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a-f, 8a-f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 microM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads.

Ab initio molecular orbital study of the reactivity of active alkyl groups. VII. Solvent effects on the formation of enolate isomers from 2-butanone with methoxide anion in methanol.

The mechanism of the deprotonation of 2-butanone (1) with methoxide anion (2) was studied by ab initio molecular orbital (MO) methods. Calculations of the thermodynamic stabilities of each complex and the regioselectivity of the reaction were performed using a static isodensity surface polarized continuum model (IPCM) which takes the solvent effect into consideration. The calculated energies of the complexes lead ultimately to the conclusion that the major deprotonation pathway in protic solvents is dependent upon thermodynamically stable complexes with small activation energies under equilibrium control.

Ab initio molecular orbital study of the reactivity of active alkyl groups. VI. Modified reaction model for the elimination process of nitrosation reaction.

The mechanisms of nitrosation of acetone through sodium enolate [CH3COCH2]- Na+ (1) or naked enolate [CH3COCH2]- (2) with tert-butyl nitrite (CH3)3CONO (3) were studied using ab initio molecular orbital (MO) methods. When the modified complex model was used in the elimination process, our results demonstrated the predominant formation of E-1-hydroxy-imino-2-oxo-propane CH3COCH=NOH (4E), in which a counter-cation of the base catalyst did not participate during the reaction. On the other hand, participation of the counter-cation during the reaction contributed to the formation of the Z-isomer of 4 (4Z).

Ab initio molecular orbital study of the reactivity of active alkyl groups. V. Nitrosation mechanism of acetone with syn-form of methyl nitrite.

The mechanisms of nitrosation of acetone through sodium enolate [CH3CO1CH2]-Na+ (1) or naked enolate [CH3CO1CH2]- (2) with methyl nitrite CH3O3NO2 (3), and the reactivity of the syn-form of 3 (syn-3) during the C-N bond formation process were investigated using ab initio molecular orbital (MO) methods. Our results have demonstrated the predominant formation of E-1-hydroxyimino-2-oxo-propane CH3COCH=NOH (4E) when the complex [CH3CO1CH2NO2(O3CH3)]-Na+ was produced kinetically via a metal-chelated pericyclic transition state (TS(CHELATED)), in which the O3 atom of syn-3 was coordinated to the Na+ atom of 1.

Solvent effect on photoisomerisation of 3-methyl-1-phenylbutane-1,2-dione 2-oxime.

Photoisomerisation of (2E)- and (2Z)-3-methyl-1-phenylbutane-1,2-dione 2-oxime (MPBDO) in several solvents was studied. With increasing dielectric constants of solvents, kinetic constants of forward reactions (E-form-->Z-form) did not change appreciably but those of reverse reactions (Z-form-->E-form) decreased. The positive correlation was found between equilibrium constants of photoisomerisation and dielectric constants of solvents.