Theoretical study of phototoxic reactions of psoralens

The phototoxic reactions between a large set of furocoumarin compounds and molecular oxygen are explored using density functional theory, using a time-dependent formalism for excited states (TD-DFT) and a continuum model to include effects of bulk solvation. The computed singlet and triplet excitation energies throughout agree very well (to within 0.2 eV) with experimental data. It is concluded that the furocoumarin compounds do display phototoxic reactions with molecular oxygen, and that they are able to generate superoxide anions as well as singlet oxygen. However, given the right conditions the generated superoxide anions will in turn serve as reducing agents for triplet psoralens, thereby efficiently scavenging the generation of reactive oxygen species. Direct electron transfer between the drugs and oxygen are also explored, as well as the effect of triplet excitation on autionisation reactions between furocoumarins.