EXPERIMENTAL: Synthetic DetailsMethods and Materials: All reagents from commercial sources were used without further purification.Reactions were carried out under nitrogen atmosphere. Solvents were dried and purified using standard techniques. Flash chromatography was performed with analytical-grade solvents using Silicycle Silica Flash P60 (particle size 40-63 µm, 60 Å, 230 -400 mesh) silica gel. Flexible plates PE SilG/UV 250µm from Whatman ® were used for TLC. Compounds were detected by UV irradiation or staining with I 2 , unless otherwise stated. All compounds were characterized by 1 H NMR (400 MHz) and 13 C NMR ( 100MHz) on a Bruker Avance III Ultrashielded 400 Plus instrument and acquired at room temperature.

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid per-

O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6-methylguanine (O6mG) in DNA that is known to cause mutation and cancer. On the basis of calculations performed using density functional theory involving the active site of AGT, a mechanism for catalytic demethylation of O6mG to guanine has been proposed. In this mechanism, roles of six amino acids, i.e., Cys145, His146, Glu172, Tyr114, Lys165, and Ser159 in catalytic demethylation of O6mG are involved. This mechanism has three steps as follows. At the first step, Cys145 in the Cys145-water-His146-Glu172 tetrad is converted to cysteine thiolate anion while at the second step, abstraction of the Tyr114 proton by the N3 site of O6mG occurs in a barrierless manner. In the third step, abstraction of Lys165 proton by deprotonated Tyr114 and transfer of the methyl group of O6mG to the thiolate group of Cys145 anion occur simultaneously. As AGT is a major target in cancer therapy, identification of the roles of the different amino acids in demethylation of O6mG is expected to be useful in designing efficient AGT inhibitors.

The dynamical behavior of the nonlinear interaction of quantum Langmuir waves (QLWs) and quantum ion-acoustic waves (QIAWs) is studied in the one-dimensional quantum Zakharov equations. Numerical simulations of coupled QLWs and QIAWs reveal that many coherent solitary patterns can be excited and saturated via the modulational instability of unstable harmonic modes excited by a modulation wave number of monoenergetic QLWs. The evolution of such solitary patterns may undergo the states of spatially partial coherence (SPC), coexistence of temporal chaos and spatiotemporal chaos (STC), as well as STC. The SPC state is essentially due to ion-acoustic wave emission and due to quantum diffraction, while the STC is caused by the combined effects of SPC and quantum diffraction, as well as by collisions and fusions among patterns in stochastic motion. The energy in the system is strongly redistributed, which may switch on the onset of weak turbulence in dense quantum plasmas.

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O6-methylguanine (O6mG) is known to be a potential mutagenic modification of guanine as it mispairs with thymine in DNA and causes GC to AT transversion mutation. It is experimentally known that O6mG can be repaired to guanine by the protein O6-alkylguanine-DNA alkyltransferase (AGT), a cysteine residue being the main active site. In the present work, the mechanisms of repair of cis-O6-methylguanine (O6mG) to guanine due to its reaction with cysteine in the absence and presence of histidine and with cysteine thiolate anion were investigated theoretically using the B3LYP hybrid functional of density functional theory and the second order Møller-Plesset perturbation (MP2) theory. Reactant, intermediate and product complexes as well as transition states involved in these reactions were fully optimized at the B3LYP/6-31 + G* level of theory in the gas phase. The solvent effect of water was treated using the polarizable continuum model (PCM). Single point energy calculations were performed at the B3LYP/AUG-cc-pVDZ and MP2/6-31 + G* levels of theory in the gas phase and aqueous media. It is found that cysteine alone can repair the cis-O6mG to guanine, but the involvement of histidine along with cysteine lowers down the barrier energy significantly. However, when cysteine thiolate anion is used in place of cysteine, the barrier energy is strongly reduced. These results broadly support the suggestions based on experimental studies.

The catalytic role of CO2 in reactions of ONOO- with guanine, leading to the formation of the mutagenic species 8-oxoguanine (8-oxoG) and 8-nitroguanine anion (8-nitroG-), was investigated by considering the reactions of nitrosoperoxycarbonate anion (ONOOCO2-), an adduct of ONOO- and CO2, with guanine at the B3LYP/6-31G** and B3LYP/AUG-cc-pVDZ levels of density functional theory in gas phase. In order to study bulk solvent effect, single-point energy calculations in aqueous media were carried out for all the species occurring in the reactions at the B3LYP/AUG-cc-pVDZ level of theory, by use of the polarizable continuum model (PCM). Vibrational frequency analysis was performed, and zero-point-energy (ZPE)-corrected total energies and Gibbs free energy changes at 298.15 K were obtained. The genuineness of the calculated transition states was confirmed by visually examining the vibrational modes and also by intrinsic reaction coordinate (IRC) calculations. The reaction between ONOOCO2- and guanine occurring through four different mechanisms leads to the formation of 8-oxoG or its anion, while the reaction between the same two species occurring through a different scheme leads to the formation of 8-nitroG-. It has been shown that the presence of a water molecule along with ONOOCO2- would not affect the reaction mechanisms significantly. Structures of the reactant complexes, product complexes and barrier energies involved in the reactions reveal that CO2 acts as a catalyst for the reaction between ONOO- and guanine. The cause of the catalytic action of CO2 is mainly due to intermediacy of the CO3 radical anion and NO2 radical into which ONOOCO2- is fragmented while reacting with guanine. The relative stabilities of the different product complexes suggest that the mutation caused by ONOO- in the presence of CO2 would mainly involve 8-oxoG.

Reaction of guanine with H2O3 in the absence and presence of a water molecule leading to the formation of 8-oxoguanine (8-oxoG) was investigated. Initial calculations were performed using imidazole (Im) as a model for the five-membered ring of guanine. The reactant, intermediate, and product complexes as well as transition states were obtained in gas phase at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels of theory. In all the cases, except for the reactions involving imidazole, single-point energy calculations were performed in gas phase at the MP2/AUG-cc-pVDZ level of theory. Solvation calculations in aqueous media were carried out using the polarizable continuum model (PCM) of the self-consistent reaction field (SCRF) theory. Vibrational frequency analysis and intrinsic reaction coordinate (IRC) calculations were performed to ensure that the transition states connected the reactant and product complexes properly. Zero-point energy (ZPE)-corrected total energies and Gibbs free energies at 298.15 K in gas phase and aqueous media were obtained. When a reaction of H2O3 in place of H2O2 with guanine is considered, the major barrier energy which is encountered at the first step is almost halved showing that H2O3 would be much more reactive than H2O2. Considering the reaction schemes investigated here and the observed fact that H2O3 is dissociated easily under ambient conditions, it appears that H2O3 would serve as an effective reactive oxygen species.