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

Jie Shao, Nicholas 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 (O2 ̇-) 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 O2 ̇- 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 O2 ̇- 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

Fingerprint

Azo Compounds
azo compounds
Deoxyguanosine
guanines
Photolysis
Guanine
photolysis
Oxidation
Tetranitromethane
Lasers
Guanosine
Free radicals
products
Superoxides
Free Radicals
Mass spectrometry
Absorption spectra
Spectroscopy
oxidation
nitroforms

ASJC Scopus subject areas

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

Cite this

Oxidative modification of guanine bases initiated by Oxyl radicals derived from photolysis of Azo compounds. / Shao, Jie; Geacintov, Nicholas; Shafirovich, Vladimir.

In: Journal of Physical Chemistry B, Vol. 114, No. 19, 20.05.2010, p. 6685-6692.

Research output: Contribution to journalArticle

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