The family of furocoumarins: Looking for the best photosensitizer for phototherapy

Furocoumarins are widely used as photosensitizers in photochemical therapies against different skin disorders such as psoriasis and vitiligo. Absorption of near-UV light by the chromophore triggers a set of photoreactions related to the therapeutic properties of the technique: linkage of a furocoumarin to thymine DNA nucleobases preventing proliferation of pathogenic cells, or generation of highly reactive singlet oxygen in damaged tissues. The family of furocoumarins has been studied in depth for many years seeking a drug having the most remarkable set of properties to act as a photosensitizer. For this purpose, understanding the underlying photochemical mechanisms behind the effectiveness of this therapy is required. We have undertaken a quantum-mechanical study on the photophysics and photochemistry of several relevant furocoumarins: psoralen, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), 4,5′,8-trimethylpsoralen (TMP), 3-carbethoxypsoralen (3-CPS), and khellin, analyzing the most efficient way in which the lowest excited triplet state, as protagonist of the photosensitizing action, is populated from the initially promoted singlet states. The results point out to khellin, in particular, and 5-MOP, as the most efficient photosensitizers.