Theoretical study on the photochemical properties of naphthazarin and halogen substitution

As a central core of quinone antitumor agents, naphthazarin (5,8-dihydroxy-1,4-naphthoquinone (NA)) has gained much attention in recent years owing to its photosensitive properties. However, there is little theoretical study on the photo-physicochemical behaviors of the compound, which stimulated our interest to perform the study by means of time-dependent density functional theory (TD-DFT) calculations. In this paper, the phototoxic reactions of NA and its halogen substitutes (NAS) were explored. The TD-DFT calculations provide various excited state properties of NAS in polar and non-polar solvents, including absorption spectra, lowest triplet excited state energies, vertical electron affinities and vertical ionization potentials, by which we can get some deeper insights into the photosensitive mechanisms of NAS. It is found that the photo-damage of NA and the substituted NA to DNA in oxygen-free media arises from NAS+. The effect of halogen substitutes is primarily a decrease of the electron affinities and thereby O2- can be generated only for NA in polar solvents. The most probable source of singlet molecular oxygen is the energy transfer from triplet excited state of NAS to molecular oxygen.