Core-modified porphyrins. Part 5: Electronic effects on photophysical and biological properties in vitro

21,23-Dithiaporphyrins 2–11 were prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin 1 to examine the impact of electronic properties at the 5- and 20-meso-positions. The effects of the electronic properties at the meso-rings were not significant with respect to absorption spectra, quantum yields for the generation of singlet oxygen and for fluorescence. While some differences were noted in the n-octanol/pH 7.4 buffer partition coefficient, log D7.4, among the compounds, log D7.4 did not critically influence the cellular uptake or phototoxicity. None of the dithiaporphyrins 1–11 displayed dark toxicity at concentrations up to 1 × 10−5 M. Once irradiated with 5 J cm−2 of 350–750 nm light, five porphyrins 2, 3, 5, 6, and 8 killed over 80% of R3230AC rat mammary adenocarcinoma cells at 5 × 10−7 M photosensitizer. Among these five, compound 3 bearing 5-phenyl and 20-(4-fluorophenyl) substituents was the most potent photosensitizer toward R3230AC cells showing 67% cell kill at 1 × 10−7 M 3. Bulky substituents at the 5- and 20-positions gave photosensitizers with minimal phototoxicity.

Figure optionsDownload as PowerPoint slide