Models of DNA C1‘ Radicals. Structural, Spectral, and Chemical Properties of the Thyminylmethyl Radical and the 2‘-Deoxyuridin-1‘-yl Radical

Abstract

The thyminylmethyl radical and the 2‘-deoxyuridin-1‘-yl radical were studied. 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 thyminylmethyl 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) × 107 M-1 s-1. The 2‘-deoxyuridin-1‘-yl radical was produced in bulk photolyses from both diastereomers of the corresponding C1‘ tert-butyl ketone, 1‘-pivaloyl-2‘-deoxyuridine, and in LFP studies from one diastereomer. Trapping of this C1‘ radical with 2-mercaptoethanol, cysteine, or glutathione gave both anomers of 2‘-deoxyuridine; the product ratios were similar in each case and insensitive to precursor identity or thiol concentrations. Rate constants for reactions of the 2‘-deoxyuridin-1‘-yl radical with thiols and metal ions were determined by LFP methods; the respective rate constants for reactions with 2-mercaptoethanol, cysteine, glutathione, CuCl2, and FeCl3 in water at ambient temperature are (2.3 ± 0.5) × 106, (2.9 ± 0.4) × 106, (4.4 ± 0.3) × 106, (7.9 ± 0.3) × 107, and ca. 1 × 108 M-1 s-1. The 2‘-deoxyuridin-1‘-yl radical was addressed computationally. The radical center is not planar, and an energy 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 with the experimentally measured UV−visible spectra.