title: Water soluble, core-modified porphyrins. 3. Synthesis, photophysical properties, and in vitro studies of photosensitization, uptake, and localization with carboxylic acid-substituted derivatives.
abstract: 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 lambda(max) of 695-701 nm. The number of carboxylic acid groups in the dithiaporphyrins 1-4 had little effect on either absorption maxima (lambda(max) of 696-701 nm for band I) or quantum yields of singlet oxygen generation [phi((1)O(2)) of 0.74-0.80]. Substituting two Se atoms for S gave a shorter band I absorption maximum (lambda(max) of 695 nm) and a smaller value for the quantum yield for generation of singlet oxygen [phi((1)O(2)) 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.
authors.affiliation: Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260-3000, USA.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: You
authors.forename: Scott L
authors.initials: SL
authors.lastname: Gibson
authors.forename: Russell
authors.initials: R
authors.lastname: Hilf
authors.forename: Sherry R
authors.initials: SR
authors.lastname: Davies
authors.forename: Allan R
authors.initials: AR
authors.lastname: Oseroff
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Tymish Y
authors.initials: TY
authors.lastname: Ohulchanskyy
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Detty
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology; D003624:Darkness; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D005453:Fluorescence; D008027:Light; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D026082:Singlet Oxygen / Q000737:chemistry; D012995:Solubility; D013053:Spectrophotometry; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D026082:Singlet Oxygen; D017323:Dihematoporphyrin Ether; D003576:Electron Transport Complex IV