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 D_7.4, among the compounds, log D_7.4 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.