Thiyl radical reaction with thymine: absolute rate constant for hydrogen abstraction and comparison to benzylic C-H bonds.
Free radical damage of DNA is a well-known process affecting biological tissue under conditions of oxidative stress. Thiols can repair DNA-derived radicals. However, the product thiyl radicals may also cause biological damage. To obtain quantitative information on the potential reactivity with DNA components, we measured the rate constant for hydrogen abstraction by cysteamine thiyl radicals from thymine C5-CH(3), k = (1.2 +/- 0.8) x 10(4) M(-1) s(-1), and thymidine-5'-monophosphate, k = (0.9 +/- 0.6) x 10(4) M(-1) s(-1). Hence, the hydrogen abstraction from C5-CH(3) occurs with rate constants similar to the hydrogen abstraction from the carbohydrate moieties. Especially at low oxygen concentration such as that found in skeletal muscle, such hydrogen abstraction processes by thiyl radicals may well compete against other dioxygen-dependent reactions. The rate constants for hydrogen abstraction at thymine C5-CH(3) were compared to those with benzylic substrates, toluenesulfonic acid, and benzyl alcohol.
Nauser
Thomas
T
Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Avenue, Lawrence, Kansas 66047, USA.
Schöneich
Christian
C
D000578:Amidines / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry* / Q000378:metabolism; D001557:Benzenesulfonates / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D003543:Cysteamine / Q000737:chemistry / Q000378:metabolism; D003903:Deuterium / Q000737:chemistry; D005609:Free Radicals / Q000138:chemical synthesis* / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D013941:Thymine / Q000737:chemistry*; D014105:Tosyl Compounds / Q000737:chemistry
D000578:Amidines; D001555:Benzene Derivatives; D001557:Benzenesulfonates; D005609:Free Radicals; D014105:Tosyl Compounds; D003543:Cysteamine; C046728:2,2'-azobis(2-amidinopropane); D006859:Hydrogen; D003903:Deuterium; D019905:Benzyl Alcohol; C029501:4-toluenesulfonic acid; D013941:Thymine