Theoretical Research The Reaction Of OH Radical With Base Pair In Nucleic Acid

DNA/RNA damage is one of the hot topics in various fields, such as chemistry biology, molecular biology and medical biology. DNA records the most genetic information of living organisms whereas the RNA brings the necessary codes to convert the information in functional products. However, DNA/RNA can be damaged by normal metabolic activities and environmental affects, in particular the effects of radiation. These damages could give rise to several diseases, such as cancer, cell aging, cardiovascular disorder and lethal lesions of biosystem. In the nearly two decades, investigating the chemical reaction mechanism of ROS with nucleobases both in experimentally and theoretically is extremely significant with regard to DNA and RNA oxidative damage in living cells. Especially, OH radical, as an electron-deficient radical, mainly reacts with nucleobases by abstraction the hydrogen atoms from the base units or through addition modes on the base units.In this paper, we study the abstraction reaction and addition reaction mechanisms of OH radical with DNA、RNA base pair by using the density functional theory. Firstly, seven possible pathways in the hydroxylation reaction of G.C base pair are investigated both in gas phase and in aqueous phase, And discovering that all discussed pathways in gas phase are thermodynamically exothermic and the reaction energy decreases in the order of G.CC4 > GC5.C > GC2.C > GC4.C > G.CC5 > G.CC6 > GC8.C. The hydroxylation reactions at G.CC5 and GC8.C site appear to be barrierless in kinetics, and the sequence of the barrier energy is G.CC4 > GC4.C > GC2.C > GC5.C > G.CC6 > G.CC5 ~ GC8.C. The results indicate that hydroxylation at GC8.C, G.CC5 and G.CC6 are more thermodynamically and kinetically favorable than other sites in G.C base pair, the results are consistent with the experimental observations. In aqueous phase, the stabilities of all the compounds are increased significantly. Little change is taken place on the data of the reaction energies and barrier energies. Their sequences and the stability order follow the same trends like them in gas phase.Secondly, we study the dehydrogenation reaction of G.C base pair in water solution, the results indicate that all the abstraction reactions in GC base pair are thermodynamically exothermic,and the stability of dehydrogenation radicals is in the sequence:(H2b-GC)? >(GC-H4b)? >(GC-H6)? >(GC-H5)?-(H8-GC)?, the reaction energy in H2 b abstraction pathway is the lowest one compared with others pathways, indicated that reaction conversion of(H2b-GC)? would be the highest. In the five hydrogen abstraction pathways the local energy barriers with respect the corresponding reactant complexes follow the sequence: H2b<H4b<H5<H6<H8, which suggeststhat the H2 b abstraction pathway in kinetics view would bethe most rapid. H2 b abstraction process would be the most favorable reaction pathway, and the compatible pathway is the H4 b abstraction and it is followed by H5 and H6 abstraction pathways both in thermodynamics and in kinetics. H8 abstraction process has the least reaction probably, which is consistent with experimentally observed hydroxylation adduct, not hydrogen abstraction radical.Finally, we investigated the reaction mechanism of OH radical with A.U base pair both in gas phase and in water solution. The results suggest that all the reaction pathways are exothermic in energy, and the relative free energies of adducts in the addition reaction are lower than those obtained for products in hydrogen abstraction reaction. Among dehydrogenation reaction in gas phase, the reactivity in thermodynamics for the dehydrogenation pathways follows this order: AN6.U > AC2.U > A.UC6 > AC8.U > A.UC5, the reaction probability for the different sites in kinetics is in the order of AN6.U > AC2.U > A.UC6 > A.UC5 > AC8.U. In aqueous phase, the reactivity is consistent with that in gas phase, but the the reaction probability for the different sites in kinetics is in the order of AN6.U > AC2.U > A.UC5 > A.UC6 > AC8.U. The results indicate that the dehydrogenation reaction at AN6.U site seems to be most favorable in thermodynamics and in kinetics, and the dehydrogenation reactions in AC2.U and AN6.U pathways are more favorable than that in AC8.U, A.UC5, A.UC6 pathways. In the hydroxylation reaction of A.U base pair A.U base pair, the reactivity sequence of the different channels is AC8.U > A.UC6 > A.UC5 > AC2.U > AC5.U > AC4.U in gas phase, the reaction tendency in kinetics is in the sequence of AC8.U > A.UC5 > A.UC6 > AC5.U > AC2.U > AC4.U. The reactivity follows the sequence AC8.U > A.UC6 > AC2.U > A.UC5 > AC5.U > AC4.U in water solution, and the reaction tendency in kinetics is line with that in gas phase. The resluts indicate that hydroxylation at AH8.U site is highly favorable both in thermodynamics and in kinetics, the results are agreement with the experimental observations, and hydroxylation at AC8.U, A.UC5, A.UC6 sites are more probable than other investigated positions.G.C and A.U base pair selected as the models in the study of reactions of OH radical with DNA and RNA are the innovations in this paper since base pairs contribute to the folded structure of both DNA and RNA. At the same time, investigating the reaction mechanism of DNA/RNA oxidative damage caused by OH radical is of great importance in drug development, disease diagnosis and other fields, and studying the damage mechanisms play a vital role in designing new high detection sensitivity biosensor.