Abstract
The 8-(arylamino)-2'-deoxyguanosines, or C-8 adducts, are the major adducts formed by reaction of N-arylnitrenium ions derived from carcinogenic and mutagenic amines with 2'-deoxyguanosine (d-G) and guanosine residues of DNA. The hydrolysis kinetics of three C-8 adducts 1a-c were determined by UV and HPLC methods at 20 degrees C under acidic, neutral, and mildly alkaline conditions. At pH < 2 the dominant hydrolysis process is spontaneous cleavage of the C-N bond of the doubly protonated substrate, 1H(2)(+2) (Scheme 2). The C-8 adducts are 2- to 5-fold more reactive than d-G under these conditions. At 3 < pH < 6 the hydrolysis kinetics are dominated by cleavage of the C-N bond of the monoprotonated nucleoside 1H(+). Under these conditions the hydrolysis kinetics are accelerated by 40- to 1300-fold over that of d-G. The rate increase appears to be caused by a combination of steric acceleration of C-N bond cleavage and a decrease in the ionization constant of 1H(+), K(a1), due to the electron-donating properties of the arylamino C-8 substituent. Under neutral pH conditions a slow (k(obs) approximately 10(-8) s(-1) to 5 x 10(-7) s(-1)) spontaneous cleavage of the C-N bond of the neutral nucleoside, 1, occurs that has not been prev...Continue Reading
References
Mar 1, 1977·Nucleic Acids Research·F Jordan, H Niv
Jan 1, 1968·Zeitschrift Für Naturforschung. Teil B. Anorganische Chemie, Organische Chemie, Biochemie, Biophysik, Biologie·J Clauwaert, J Stockx
Sep 12, 1972·Biochemistry·T Lindahl, A Andersson
Jun 28, 1972·Journal of the American Chemical Society·R P PanzicaL B Townsend
Dec 14, 1971·Journal of Molecular Biology·J H NelsonI B Weinstein
Oct 1, 1969·Chemico-biological Interactions·E Kriek
Mar 25, 1970·Journal of the American Chemical Society·E J Del Rosario, G G Hammes
Jan 1, 1967·Biochemistry·E KriekE C Miller
May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·P L FosterJ H Miller
Oct 28, 1980·Biochemistry·N R DrinkwaterJ A Miller
Jul 24, 1982·Nucleic Acids Research·H Lönnberg, P Lehikoinen
Jun 1, 1980·Carcinogenesis·E Kriek, J G Westra
Mar 30, 1995·Chemico-biological Interactions·C P SarisJ F Stavenuiter
Feb 12, 1998·Chemical Research in Toxicology·W PfauU Brockstedt
Mar 1, 1962·Journal of Molecular Biology·S GREER, S ZAMENHOF
Citations
Jun 1, 2011·European Journal of Organic Chemistry·Heidi A Dahlmann, Shana J Sturla
Jul 4, 2013·The Journal of Organic Chemistry·Michael S KuskaRichard A Manderville
Dec 31, 2019·Chemical Research in Toxicology·Trevor W ManningStacey D Wetmore