Curcumin is known to be an antioxidant, as it can scavenge free radicals from biological media. A sequence of H-abstraction and addition reactions involving up to eight OH radicals and curcumin or its degradation products leading to the formation of two other antioxidants, namely, ferulic acid and vanillin, was studied. Single electron transfer from curcumin to an OH radical was also studied. All relevant extrema on the potential energy surfaces were located by optimizing geometries of the reactant and product complexes, as well as those of the transition states, at the BHandHLYP/6-31G(d,p) level of density functional theory in the gas phase. Single-point energy calculations were also performed in the gas phase at the BHandHLYP/aug-cc-pVDZ and B3LYP/aug-cc-pVDZ levels of theory. Solvent effects in aqueous media were treated by performing single-point energy calculations at all of the above-mentioned levels of theory employing the polarizable continuum model and the geometries optimized at the BHandHLYP/6-31G(d,p) level in the gas phase. A few reaction steps were also studied by geometry optimization in aqueous media, and the thus-obtained Gibbs free energy barriers were similar to those obtained by corresponding single-point energy calculations. Our calculations show that the hydrogen atom of the OH group attached to the phenol moiety of curcumin would be most efficiently abstracted by an OH radical, in agreement with experimental observations. Further, our study shows that OH addition would be most favored at the C10 site of the heptadiene chain. It was found that curcumin can serve as an effective antioxidant.

The enzyme adenine DNA glycosylase, also called MutY, is known to catalyze base excision repair by removal of adenine from the abnormal 2'-deoxyadenosine:8-oxo-2'-deoxyguanosine pair in DNA. The active site of the enzyme was considered to consist of a glutamic acid residue along with two water molecules. The relevant reaction mechanism involving different barrier energies was studied theoretically. Molecular geometries of the various molecules and complexes involved in the reaction, e.g., the reactant, intermediate, and product complexes as well as transition states, were optimized employing density functional theory at the B3LYP/6-31G(d,p) level in the gas phase. It was followed by single-point energy calculations at the B3LYP/AUG-cc-pVDZ, BHandHLYP/AUG-cc-pVDZ, and MP2/AUG-cc-pVDZ levels in the gas phase. Single-point energy calculations were also carried out at the B3LYP/AUG-cc-pVDZ and BHandHLYP/AUG-cc-pVDZ levels in aqueous media as well as in the solvents chlorobenzene and dichloroethane. For the solvation calculations, the integral equation formalism of the polarizable continuum model (IEF-PCM) was employed. It is found that glutamic acid along with two water molecules would effectively cleave the glycosidic bond of adenosine by a new two-step reaction mechanism proposed here which is different from the three-step mechanism proposed by other authors earlier regarding the working mechanism of MutY.

The reaction between nitrogen dioxide (NO2*) and guanine radical cation (G*+) yielding the mutagenic product 8-nitroguanine radical cation (8-nitroG*+) was studied in the presence of one or two water molecules. All the relevant extrema on the potential energy surface were located by fully optimizing the geometries of the reactant, intermediate, and product complexes as well as transition states at the B3LYP/6-31G**, B3PW91/6-31G**, B3LYP/AUG-cc-pVDZ, and B3PW91/AUG-cc-pVDZ levels of density functional theory in gas phase. Zero point energy-corrected total energies and the corresponding Gibbs free energies at 298.15 K were obtained at the B3LYP/AUG-cc-pVDZ and B3PW91/AUG-cc-pVDZ levels of theory. Single point energy calculations were performed for all the optimized geometries at the MP2/AUG-cc-pVDZ level of theory in gas phase. Solvent effect of aqueous media was treated by performing single point energy calculations at the B3LYP/ AUG-cc-pVDZ, B3PW91/AUG-cc-pVDZ, and MP2/AUG-cc-pVDZ levels of theory employing the polarizable continuum model. The solvent effect of bulk water as well as that due to specific water molecules were found to play very important roles in lowering down many barrier energies appreciably. It is found that 8-nitroG*+ complexed with water molecules would be formed due to the reaction of G*+ with NO2* in aqueous media. The possible biological significance of the results obtained has been examined by studying binding energies of several normal and abnormal base pairs.

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N-Acetylcysteine, a precursor of glutathione, is an effective antioxidant present in biological systems. The mechanism of scavenging action of N-acetylcysteine for the OH radical was studied theoretically. For this purpose, reactions of the OH radical at the different sites of N-acetylcysteine were investigated. All the relevant extrema on the potential energy surfaces were located by optimizing the geometries of the reactant and product complexes as well as those of the transition states at the BHandHLYP/AUG-cc-pVDZ level of density functional theory in the gas phase. The solvent effect of aqueous media was treated by performing single point energy calculations at the BHandHLYP/AUG-cc-pVDZ and MP2/AUG-cc-pVDZ levels of theory employing the polarizable continuum model. Correction for basis set superposition error (BSSE) was made by the counterpoise method. Rate constants for all the reaction mechanisms were calculated including the tunneling contributions. Our calculations show that the hydrogen atom of the SH group of N-acetylcysteine would be most efficiently abstracted by the OH group, which is in agreement with experimental observations.