6533b861fe1ef96bd12c4472

RESEARCH PRODUCT

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

subject

description

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 micro environment 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-S-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.