Isoguanine Formation from Adenine

Abstract

Several possible mechanisms underlying isoguanine formation when OH radical attacks the C2 position of adenine (A) are investigated theoretically for the first time. Two steps are involved in this process. In the first step, one of two low‐lying A⋅⋅⋅OH reactant complexes is formed, leading to C2H2 bond cleavage. Between the two reactant complexes there is a small isomerization barrier, which lies well below separated adenine plus OH radical. The complex dissociates to free molecular hydrogen and an isoguanine tautomer (isoG 1 or isoG 2). The local and activation barriers for the two pathways are very similar. This evidence suggests that the two pathways are competitive. After dehydrogenation, there are two possible routes for the second step of the reaction. One is direct hydrogen transfer, via enol–keto tautomerization, which has high local barriers for both tautomers and is not favored. The other option is indirect hydrogen transfer involving microsolvation by one water molecule. The water lowers the reaction barrier by over 20 kcal mol−1, indicating that water‐mediated hydrogen transfer is much more favorable. Both A+OH.→isoG+H. reactions are exothermic and spontaneous. Among four isoguanine tautomers, isoG 1 has the lowest energy. Our findings explain why only the N1H and O2H tautomers of isolated isoguanine and isoguanosine have been observed experimentally.

DFT study of adenine‐uracil base pair damage by OH radical

“…is the least favorable one. In the dehydrogenation reaction of isolated adenine, previous studies pointed that [A N6 ] is more favorable than others, except [A N9 ], and [A C8 ] is the most unfavorable. In the dehydrogenation reaction of A·T base pair, Kurita et al .…”

“…In previous works, the dehydrogenation and hydroxylation reactions of adenine have been studied theoretically for their structures and energetic stability. The stability sequence of the dehydrogenated radicals is [A N9 ] > [A N62 ] > [A N61 ] > [A C2 ] > [A C8 ] reported by Schaefer et al . and Zhang et al , and the barrier energy with respect to reactant complexes for the dehydrogenation reaction at five sites is in the sequence of A N62 < A N9 < A N61 < A C2 < A C8 reported by Schaefer et al Mishra et al pointed that the relative free energies of different adenine radical follows the order [A N9 ] < [A N62 ] < [A N61 ] at the different levels of theory.…”

“…The stability sequence of the dehydrogenated radicals is [A N9 ] > [A N62 ] > [A N61 ] > [A C2 ] > [A C8 ] reported by Schaefer et al . and Zhang et al , and the barrier energy with respect to reactant complexes for the dehydrogenation reaction at five sites is in the sequence of A N62 < A N9 < A N61 < A C2 < A C8 reported by Schaefer et al Mishra et al pointed that the relative free energies of different adenine radical follows the order [A N9 ] < [A N62 ] < [A N61 ] at the different levels of theory. The stability order of adducts for the hydroxylation of isolated adenine is A C8‐OH > A C2‐OH > A C6‐OH > A C4‐OH > A C5‐OH , and the reaction barriers energy with respect to reactant complexes for five pathways is A C8 < A C5 < A C4 < A C6 < A C2 reported by Zhang et al As the simplest pyrimidine base of RNA, the reactions of uracil with OH radical have been studied theoretically.…”

Mass spectrometry for the assessment of the occurrence and biological consequences of DNA adducts

“…This radical can bind to pyrimidine bases with a preference for the C5 and C6 positions, generating C5–OH– and C6–OH-adduct radicals, respectively; it can also conjugate with purine bases, giving rise to C4–OH–, C5–OH–, and C8–OH-adduct radicals for both guanine and adenine 55,56 as well as a C2–OH-adduct radical for adenine. 57,58 Examples of hydroxyl radical-induced DNA adducts include 5-hydroxyuracil (5-OH-Ura), 5-hydroxycytosine (5-OH-Cyt), 5,6-dihydroxy-5,6-dihydrothymine (a.k.a. thymine glycol), and 8-oxo-7,8-dihydroguanine (8-oxo-Gua).…”

Expanding a fluorescent RNA alphabet: synthesis, photophysics and utility of isothiazole-derived purine nucleoside surrogates

“…10 Isoguanine, for example, is a reported product of oxidative damage to DNA. 11 2-Aminoadenosine is a known analogue of adenosine that engages in three hydrogen bonds of the W-C type, adding considerable stability to the double helix. 12 Xanthine is a known product of deamination of nucleobases, a sign of miscoding and mutagenesis in DNA and RNA.…”