Hydroxyl Radical Reactions with Adenine: Reactant Complexes, Transition States, and Product Complexes

Abstract

In order to address problems such as aging, cell death, and cancer, it is important to understand the mechanisms behind reactions causing DNA damage. One specific reaction implicated in DNA oxidative damage is hydroxyl free-radical attack on adenine (A) and other nucleic acid bases. The adenine reaction has been studied experimentally, but there are few theoretical results. In the present study, adenine dehydrogenation at various sites, and the potential-energy surfaces for these reactions, are investigated theoretically. Four reactant complexes [A···OH]* have been found, with binding energies relative to A+OH* of 32.8, 11.4, 10.7, and 10.1 kcal mol(-1). These four reactant complexes lead to six transition states, which in turn lie +4.3, -5.4, (-3.7 and +0.8), and (-2.3 and +0.8) kcal mol(-1) below A+OH*, respectively. Thus the lowest lying [A···OH]* complex faces the highest local barrier to formation of the product (A-H)*+H(2)O. Between the transition states and the products lie six product complexes. Adopting the same order as the reactant complexes, the product complexes [(A-H)···H(2)O]* lie at -10.9, -22.4, (-24.2 and -18.7), and (-20.5 and -17.5) kcal mol(-1), respectively, again relative to separated A+OH*. All six A+OH* → (A-H)*+H(2)O pathways are exothermic, by -0.3, -14.7, (-17.4 and -7.8), and (-13.7 and -7.8) kcal mol(-1), respectively. The transition state for dehydrogenation at N(6) lies at the lowest energy (-5.4 kcal mol(-1) relative to A+OH*), and thus reaction is likely to occur at this site. This theoretical prediction dovetails with the observed high reactivity of OH radicals with the NH(2) group of aromatic amines. However, the high barrier (37.1 kcal mol(-1)) for reaction at the C(8) site makes C(8) dehydrogenation unlikely. This last result is consistent with experimental observation of the imidazole ring opening upon OH radical addition to C(8). In addition, TD-DFT computed electronic transitions of the N(6) product around 420 nm confirm that this is the most likely site for hydrogen abstraction by hydroxyl radical.

On the Participation of Photoinduced N–H Bond Fission in Aqueous Adenine at 266 and 220 nm: A Combined Ultrafast Transient Electronic and Vibrational Absorption Spectroscopy Study

“…77 Together, this evidence leads us to conclude that the persisting absorption signature between 340 and 360 nm in Figure 3b after t ≈ 10 ps is indeed due to the red-edge of the 300 -400 nm absorption band of neutral Ade[-H] radicals. An example TEA spectrum at t = 10 ps is overlaid in Figure 3c for comparison.…”

Hydroxyl Radical (OH•) Reaction with Guanine in an Aqueous Environment: A DFT Study

“…10e–j,12,13 Considering the optimized hydrated structures of adduct, ion-pair and radical, single point energy calculations were done to take into account the effect of full solvation through the use of IEF-PCM model, see Table 1. Our calculations show that the B3LYP/6-31G* and B3LYP/6-31++G** give similar results, see Table 1, thus in the text, we discuss our results derived from B3LYP/6-31G* calculations unless otherwise stated.…”

“…In keeping with Chatgilialoglu’s interpretation that H-atom abstraction processes dominate and using the B3LYP/DZP++ level of theory, Cheng et al 12 recently studied the OH • -induced hydrogen atom abstraction reaction from the different sites of adenine. Direct hydrogen atom abstraction reaction from guanine’s exocyclic NH 2 group by OH • in the gas-phase using Car–Parinello molecular dynamics (MD) was also reported by Mundy et al 13a However, in a later study from this group, the dehydrogenation reaction from four sites (N 1 , N 2 , N 9 and C 8 ) of guanine by OH • was carried out in an aqueous phase of many explicit water molecules.…”

Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties

“…HO · can oxidize almost all biological molecules through 3 main reaction types: hydrogen abstraction, addition and electron transfer . HO · can abstract hydrogen atoms from some compounds, including H 2 O and ethyl alcohol, and add to guanine and unsaturated fatty acids, forming other radicals . HO · can also react with chemical groups (nitrite, bicarbonate ion) or ions (halide ions) .…”