To optimize a hypericin derivative as a potential photodynamic therapy agent its light-induced singlet oxygen/superoxide radical formation capability should be enhanced and its long-wavelength absorption band should be bathochromically shifted to better match medicinal lasers. A heavy-atom–substituted derivative was realized by electrophilic iodination of hypericin to yield 2,5-diiodo-hypericin. Using photodestruction of bilirubin IXα this derivative was demonstrated to exhibit an enhanced light-induced singlet oxygen/superoxide radical formation capability as compared to hypericin. With respect to a bathochromically shifted derivative styryl residues were attached to the methyl groups of hypericin by de novo ring synthesis. Although the long-wavelength absorption band of this derivative displayed a bathochromic shift of nearly 40 nm it unfortunately immediately underwent an intramolecular [2 2] cycloaddition to yield the corresponding cyclobutane derivative in which the added conjugation system became interrupted.