DFT Study of the Hydroxyl Radical Addition to 2′-Deoxyguanosine and the Guanine Base in Four Double-Stranded B-Form Dimers

Abstract

Density functional theory (DFT) calculations of reactions between 2′-deoxyguanosine (dR-Gua) and hydroxyl radical (HO • ) with water molecules (H 2 O) n , n = 0, 1, and 2, were carried out. The HO • addition to three carbon sites, C(4), C(5), and C(8), and the subsequent ring cleavage of the three HO adducts were investigated. The addition to C( 5) is of the smallest activation energy according to the largest lobe of the dR-Gua highest occupied molecular orbital (HOMO) at C(5). However, its adduct has small stability, and the C(8) adduct has the largest one. The C(8) adduct and the ring-opened amide have similar stability, which would lead to the apparent small yield of the former. Calculations were also performed on HO • additions to the C(4) and C(8) sites of the guanine moiety of four dimer sequence models of B-form DNA with nucleotide moieties (a) 5′-GA-3′, (b) 5′-GG-3′, (c) 5′-GT-3′, and (d) 5′-GC-3′. For instance, the (a) 5′-GA-3′ model has a molecular formula C 39 H 50 N 15 Na 2 O 21 P 2 . The HO • attack to C(4) is ruled out owing to the reinforced deformation of the parallel stacking of base pairs. The clear selectivity that the (b) 5′-GG-3′ sequence is most reactive was found with the inclusion of the water dimer.

Influence of hydrogen bonds on the reaction of guanine and hydroxyl radical: DFT calculations in C(H+)GC motif

“…12 The reaction of HO attachment to G is exothermic in nature, manifested by the greater stability of Int2 (27.5 kJ mol À1 ) and Int9 (6.8 kJ mol À1 ) with respect to separated HO and Tri, where the stabilization energies of hydroxylated G at C4 and C5 in an unrestricted context are 74.9 and 49.8 kJ mol À1 , respectively. 12 Herein, optimized geometries and energetics for the reaction of hydroxylation in the C(H + )GC context are very consistent with previous studies for free G and G in a duplex context, 12,15,18 further confirming the feasibility of the selected model for calculation.…”

“…The destabilizing complexes (Int1 and Int8) are easily transformed to hydroxylation products (Int2 and Int9) via TS1 and TS5 with forward energy barriers of 35.1 and 5.8 kJ mol À1 , respectively, which are higher than the barrierless hydroxylation of free G and similar to that in the dimer sequence model of B-form DNA with nucleotide moieties (33.5 kJ mol À1 for C4). 12,18 The transition state (TS) of hydroxylation at the C4 and C5 sites of G is characterized by the elongated C4-C5 bond as well as the shortened distances of C4Á Á ÁO(HO ) (TS1) and C5Á Á ÁO(HO ) (TS5), which are continuously reduced to 1.42 and 1.44 Å, leading to adduct radicals Int2 (G(C4-OH) ) and Int9 (G(C5-OH) ). The hydroxylation at C4 and C5 incurs appreciable nonplanarity of G similar to the butterfly shape referred to in previous studies.…”

“…Indeed, the reactions of HO with free G have been extensively studied using various experimental techniques and theoretical methods (Scheme 1). [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Initially, the reactions were studied by O'Neill and his co-workers using pulse radiolysis, 7 where addition reactions at the C4, C5, and C8 atoms of G were predicted to be the dominant pathway. Afterward, Candeias and Steenken revisited the reactions and proposed that the addition reaction of HO with G at C4 and C5 sites leading to G(C4-OH) and G(C5-OH) dominates (B60-70%) over the addition to its C8 site forming G(C8-OH) (B17%).…”

Do We Still Need a Laboratory to Study Advanced Oxidation Processes? A Review of the Modelling of Radical Reactions used for Water Treatment

“…Besides, the energies computed by QCC can have an accuracy of < 2 kcal/mol, which is similar to that of many of those determined experimentally [12]. QCC can also be used for many other tasks other than the degradation of pollutants, such as studying the modification of nanomaterials [13], determining the reaction mechanism with DNA components [14][15][16][17] and other biomolecules present in a mammal's body [18][19][20]. ) the same but in one dimension.…”

Theoretical insights into the reaction mechanism of hydroxyl radicals and guanine in G-quadruplex DNA

“…To date, numerous efforts have been made to illuminate the vague reactions course of OH and guanine. [9][10][11][12][13] It has been proposed that the main reaction of OH with guanine involves its addition to unsaturated bonds and hydrogen abstraction reactions from the amino group of G as shown in Scheme 1. 13 The adduct radical at C4 (G(C4-OH) ) appears to be predominant as the highest product yield in contrast to the poorly yielded C5 (G(C5-OH) ) and C8 adduct radical (G(C8-OH) ).…”