Radical anions from 5-fluorouracil derivatives. A theoretical study of their cleavage and orbital isomerism

Theoretical calculations were performed on the dissociation of radical anio ns of 5-fluorouracils substituted at N-1. The reaction (1-CR1R2R3 -5-fluoro uracil)(-) .-->, (5-fluorouracil)(-) + R1R2R3 C . was calculated for severa l substituents R, including the N-1-C-5 dimers 1. Two main types of radical anions were observed. Radical anions of pi type have the unpaired spin den sity located at the carbonyl and C-C double bond conjugated system of the u racil ring while the a species present unpaired spin density mainly at the N-1-C(R1R2R3) bond. The electronic nature of the most stable radical anion was found to be determined by the electron affinity of the substituent at N -1. The activation barrier for the cleavage of pi radical anions arises from it s avoided crossing with the a potential surface. The a radical anions, whic h have stabilised SOMOs, dissociate with lower activation barriers than the pi intermediates. These observations correlate with the lengthening and in crement of unpaired spin density at their N-1-C bond. Gas phase calculation s are compared with results in aqueous solution. Other fragmentation paths are proposed for substituents like R=NO2 or halogen. (C) 2000 Elsevier Scie nce B.V. All rights reserved.