Models of DNA C1 ' radicals. Structural, spectral, and chemical propertiesof the thyminylmethyl radical and the 2 '-deoxyuridin-1 '-yl radical

The thyminylmethyl radical and the 2'-deoxyuridin-1'-yl radical were studie d. The former radical was produced in laser flash photolysis (LFP) studies from two precursors derived from thyminylacetic acid, the N-hydroxypyridine -2-thione ester (PTOC ester), and the phenylselenyl ester. The thyminylmeth yl radical has an absorbance in the range 315-340 nm. The rate constant for its reaction with octadecanethiol in THF at ambient temperature determined by LFP methods is (3.1 +/- 0.6) x 10(7) M-1 s(-1). The 2'-deoxyuridin-1'-y l radical was produced in bulk photolyses from both diastereomers of the co rresponding C1' tert-butyl ketone, 1'-pivaloyl-2'-deoxyuridine, and in LFP studies from one diastereomer. Trapping of this C1' radical with 2-mercapto ethanol, cysteine, or glutathione gave both;anomers of 2'-deoxyuridine; the product ratios were similar in each case and insensitive to precursor iden tity or thiol concentrations. Rate constants for reactions of the 2'-deoxyu ridin-1'-yl radical with thiols and metal ions were determined by LFP metho ds; the respective rate constants for reactions with 2-mercaptoethanol, cys teine, glutathione, CuCl2, and FeCl3 in water at ambient temperature are (2 .3 +/- 0.5) x 10(6), (2.9 +/- 0.4) x 10(6), (4.4 +/- 0.3) x 10(6), (7.9 +/- 0.3) x 10(7), and ca. 1 x 10(8) M-1 s(-1). The 2'-deoxyuridin-1'-yl radica l was addressed computationally. The radical center is not planar, and an e nergy profile for interconversion of the two anomeric forms of the radical was produced. Computed vertical transitions for the thyminylmethyl radical and one anomer of the 2'-deoxyuridin-1'-yl radical are in good agreement wi th the experimentally measured UV-visible spectra.