Water Soluble, Core-Modified Porphyrins. 3. Synthesis, Photophysical Properties, and in Vitro Studies of Photosensitization, Uptake, and Localization with Carboxylic Acid-Substituted Derivatives

Water soluble, core-modified porphyrins 1−5 bearing 1−4 carboxylic acid groups were prepared and evaluated in vitro as photosensitizers for photodynamic therapy. The 21,23-core-modified porphyrins 1−5 gave band I absorption maxima with λmax of 695−701 nm. The number of carboxylic acid groups in the dithiaporphyrins 1−4 had little effect on either absorption maxima (λmax of 696−701 nm for band I) or quantum yields of singlet oxygen generation [φ(1O2) of 0.74−0.80]. Substituting two Se atoms for S gave a shorter band I absorption maximum (λmax of 695 nm) and a smaller value for the quantum yield for generation of singlet oxygen [φ(1O2) of 0.30]. The phototoxicity of 1−5 was evaluated against R3230AC cells. The phototoxicities of dithiaporphyrin 2, sulfonated thiaporphyrin 30, HPPH, and Photofrin were also evaluated against Colo-26 cells in culture using 4 J cm-2 of 570−800 nm light. Compound 2 was significantly more phototoxic than sulfonated dithiaporphyrin 30, HPPH, or Photofrin. Cellular uptake was much greater for compounds 1, 2, and 5 relative to compounds 3 and 4. Confocal scanning laser microscopy and double labeling experiments with rhodamine 123 suggested that the mitochondria were an important target for dithiaporphyrins 1 and 2. Inhibition of mitochondrial cytochrome c oxidase activity in whole R3230AC cells was observed in the dark with compounds 1 and 30 and both in the dark and in the light with core-modified porphyrin 2.