DFT mechanistic study on the formation of 8-oxoguanine and spiroiminodihydantoin mediated by iron Fenton reactions. Issue 28 (30th June 2021)

• Record Type: Journal Article
• Authors: Chen, Hsing-Yin; Lin, Yu-Fen
• Is Part Of: Dalton transactions. Volume 50:Issue 28(2021)
• Page Start: 9842
• Page End: 9850
• Publication Date: 2021-06-30
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d1dt01508g
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : The Fenton oxidation mediated by guanine N7-bound iron(ii ) leads to the formation of 8-oxoguanine and spiroiminodihydantoin through multiple reaction pathways involving hydroxyl radical and high-valent iron(iv )-oxo species. Abstract : Fenton reactions unavoidably take place in the human body and have been demonstrated to cause oxidative DNA damage. However, the molecular-level understanding of DNA damage mediated by Fenton reactions is limited. Herein, density functional theory (DFT) calculations were made to investigate the counterion effects on aqueous Fenton reactions and the detailed mechanisms of chemical modifications to guanine induced by Fenton reactions. Our calculations show that the activation energy of the Fenton reaction catalyzed by a pure aquo complex [Fe II (H2 O)6 ] 2+ is too high to agree with experiments, whereas complexation with counteranions reduces the activation energy to a reasonable range. This result suggests that Fe II -counteranion complexes are the real catalyst for fast aqueous Fenton reactions. In addition, we found that the Fenton oxidation mediated by Fe II bonded to the N7 atom of guanine can result in the formation of 8-oxoguanine and spiroiminodihydantoin through multiple reaction pathways, including the electrophilic addition of ˙OH, H-abstraction by ˙OH, and oxygen atom transfer of oxoiron(iv ) species. The activation of hydrogen peroxide by ferrous iron is the rate-determining step. The guanine N7-bound iron ion and the coordinated counteranion were found to play an important role in the Fenton oxidation of guanine.