Core-modified porphyrins. Part 4: Steric effects on photophysical and biological properties in vitro

Abstract

21,23-Dithiaporphyrins ( 2– 10) were designed and prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin ( 1) to examine the impact of steric bulk at the 5- and 20- meso positions as well as the impact of symmetry. Changes at the meso positions had minimal impact on the UV–vis–near-IR absorption spectra, quantum yields for the generation of singlet oxygen, and quantum yields for fluorescence and some impact on values of the octanol/water partition coefficient. Of the compounds 1– 10, 5-phenyl-20-(2-thienyl)-10,15-bis-(4-carboxylatomethoxy-phenyl)-21,23-dithiaporphyrin ( 3) showed the greatest phototoxicity toward cultured R3230AC cells, with 68% cell kill at 1 × 10 −7 M and irradiation with 5 J cm −2 of 350–750 nm light. Results in this study suggest that smaller substituents on the meso ring and less symmetrical compounds are more effective as photosensitizers than compounds with two bulky substituents at adjoining meso sites and a higher symmetry. The mitochondria appear to be involved in the process of phototoxicity as determined by the inhibition of whole cell cytochrome c oxidase activity in cells treated with 3 and light. No impact upon mitochondrial cytochrome c oxidase activity was observed in cells treated with 3 and no light. Fluorescence microscopy studies suggest that the mitochondria are not initial sites of accumulation of 3.