Oxidative modification of guanine bases initiated by Oxyl radicals derived from photolysis of Azo compounds

Jie Shao, Nicholas E. Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

Oxidative damage to guanine bases initiated by photolysis of the water-soluble radical generator 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In the neutral oxygenated aqueous solutions, 355 nm laser flash photolysis of AAPH generates a whole spectrum of free radicals including 2-amidinoprop-2-peroxyl (ROO ̇), 2-amidinoprop-2-oxyl (RȮ), and superoxide (O2̇-) radicals. These oxyl radicals with negligible absorption in a near UV-visible range were monitored in the reactions leading to the products with characteristic absorption spectra. This approach reveals that RȮ radicals induce fast one-electron oxidation of 2-deoxyguanosine (dG) to form guanine neutral radicals, dG(-H)̇. In contrast, ROȮ radicals do not react at observable rates with dG. The O2̇- radicals were detected using a classical test reaction with tetranitromethane to form nitroform. The major pathway for formation of the end-products of guanine oxidation is the combination of the G(-H)̇ and O2̇- radicals to form 2,5-diamino-4H-imidazolone (Iz). This mechanism was confirmed by analysis of the end-products produced by oxidation of two substrates: (1) the guanosine derivative 2,3,5-tri-O-acetylguanosine (tri-O-Ac-G) and (2) the 5-d(CCATCGCTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Iz and 5-d(CCATC[Iz]CTACC products.

Original languageEnglish (US)
Pages (from-to)6685-6692
Number of pages8
JournalJournal of Physical Chemistry B
Volume114
Issue number19
DOIs
StatePublished - May 20 2010

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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