(G–H) ^• –C and G–(C–H) ^• radicals derived from the guanine·cytosine base pair cause DNA subunit lesions

Abstract

The radicals generated by the homolytic cleavage of an X-H bond from the guanine⅐cytosine (G⅐C) base pair were studied by using carefully calibrated theoretical methods. The gradient-corrected density functional B3LYP was applied in conjunction with doubleplus polarization and diffuse function basis sets. Optimized geometries, energies, and vibrational frequencies were obtained for all of the radicals considered. Structural perturbations along with energy relaxation due to radical formation were investigated. Dissociation energies of the G⅐C base pair and all of the radicals are predicted and compared with the dissociation energy of neutral G⅐C. The three lowest-energy base pair radicals all involve removal of an H atom from one of the N atoms in G⅐C. The lowest-energy base pair radical has the hydrogen atom removed from the guanine nitrogen atom used for the sugar phosphate linkage in DNA. This (G-H) • -C radical has a dissociation energy (to G-H • ؉ C) of 30 kcal͞mol, which may be compared with 27 kcal͞mol for G⅐C. All of the radicals that are possible outcomes of direct ionizing radiation or oxidizing species were investigated for the presence of local minima with significant structural changes. Major structural deformations cause strain in the interstrand hydrogen bonding in the DNA double helix. Severe geometry changes were observed when the hydrogen was abstracted from interstrand hydrogen bonding sites, along with sizeable energy changes, indicating the potentially serious consequences to the G⅐C base pair.

Communication: UV photoionization of cytosine catalyzed by Ag+

“…[14][15][16][17]48 Usually, primary photoionization of guanine, the base with the lowest IP, 14 takes place upon direct interaction with ionizing radiation with photons near 8 eV. In this work, we show that Cyt can be also ionized, but at lower photon energies (less than 4 eV), when interacting with Ag + , through a CT state.…”

“…[7][8][9][10][11][12] Particularly interesting is the photoionization of the DNA bases (e.g., by Vacuum Ultra Violet (VUV), β, γ, or X-ray radiation) because it can develop different kinds of cancers. 5,6,[13][14][15] The genotoxic effect of ionizing radiation in living cells can be produced by secondary species generated by the primary radiation 5 or by direct interaction of the photons with the DNA bases leading to their ionization within the WC pair.…”

Energy Barrier Reduction for the Double Proton-Transfer Reaction in Guanine–Cytosine DNA Base Pair on a Gold Surface

“…Furthermore, there is a lack of experimental data about the PT in isolated base pairs. Nonetheless, the effects of ligands, 52 electron attachment 53,54 or even the effect of an external field 55 appear to be strong enough to modify the PT mechanism of DNA bases.…”

One‐electron addition on short‐loop selenylsulfide and diselenide‐linked biomolecules: From diethyldichalcogens to Grx3‐like selenopeptides

“…The double-ζ quality DZP++ basis set, that has been proposed by Schaefer and coworkers [36], is used throughout. The validity of a MP2 treatment for dissymmetric 2c-3e systems is questionnable.…”