Theoretical design of monofunctional psoralen compounds in photochemotherapy

The geometries and electronic structures in the lowest triplet (T ₁) states of psoralen, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and their monoadducts were studied by performing density functional theory (DFT) calculations. It was shown that the pyrone ring of 8-MOP is cleaved in the T₁ state and the cleaved pyrone ring loses the ability to bond to the thymine residue. Therefore, 8-MOP in the open-ring structure does not form a diadduct, which is thought to cause side effects. DFT calculations on 20 kinds of substituted psoralens showed that the cleavage of the pyrone ring in the T₁ state can be controlled by substituting an electron-donating group, especially one having a strong electron-donating resonance effect, at the 8-position of psoralen.