A Combined Experimental and Theoretical Approach to the Photogeneration of 5,6-Dihydro­pyrimidin-5-yl Radicals in Nonaqueous Media

The
chemical fate of radical intermediates is relevant to understand
the biological effects of radiation and to explain formation of DNA
lesions. A direct approach to selectively generate the putative reactive
intermediates is based on the irradiation of photolabile precursors.
But, to date, radical formation and reactivity have only been studied
in aqueous media, which do not completely mimic the microenvironment
provided by the DNA structure and its complexes with proteins. Thus,
it is also important to evaluate the photogeneration of nucleoside-based
radicals in nonaqueous media. The attention here is focused on the
independent generation of 5,6-dihydropyrimidin-5-yl radicals in organic
solvent through the synthesis of new lipophilic tert-butyl ketone precursors. Formation of 5,6-dihydro-2′-deoxyuridin-5-yl
and 5,6-dihydrothymidin-5-yl radicals has first been confirmed by
using a new nitroxide-derived profluorescent radical trap. Further
evidence has been obtained by nanosecond laser flash photolysis through
detection of long-lived transients. Finally, the experimental data
are corroborated by multiconfigurational ab initio CASPT2//CASSCF methodology.