Toward hypericin-derived potential photodynamic therapy agents

To optimize a hypericin derivative as a potential photodynamic therapy agen t its light-induced singlet oxygen/superoxide radical formation capability should be enhanced and its long-wavelength absorption band should be bathoc hromically shifted to better match medicinal lasers. A heavy-atom-substitut ed derivative was realized by electrophilic iodination of hypericin to yiel d 2,5-diiodo-hypericin. Using photodestruction of bilirubin IX alpha this d erivative was demonstrated to exhibit an enhanced light-induced singlet oxy gen/superoxide radical formation capability as compared to hypericin. With respect to a bathochromically shifted derivative styryl residues were attac hed to the methyl groups of hypericin by de novo ring synthesis. Although t he long-wavelength absorption band of this derivative displayed a bathochro mic shift of nearly 40 nm it unfortunately immediately underwent an intramo lecular [2 + 2] cycloaddition to yield the corresponding cyclobutane deriva tive in which the added conjugation system became interrupted.