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 x 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 x 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 x 10(-7) M 3. Bulky substituents at the 5- and 20-positions gave photosensitizers with minimal phototoxicity.
You
Youngjae
Y
Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA. yjyou@nsm.buffalo.edu
Gibson
Scott L
SL
Detty
Michael R
MR
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015394:Molecular Structure; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013057:Spectrum Analysis; D055672:Static Electricity
D002264:Carboxylic Acids; D017319:Photosensitizing Agents; D011166:Porphyrins