Merocyanine dyes: effect of structural modifications on photophysical properties and biological activity.
Merocyanine derivatives were prepared by structural alterations at the barbituric acid or chalcogenazole moieties. The photophysical properties of the dyes were markedly influenced by the presence of selenium rather than sulfur as a substituent at position 2 of the barbiturate. In methanol, quantum yields of both triplet state (phi T) and singlet oxygen sensitization (phi delta) were increased by over an order of magnitude, with a concomitant decrease in fluorescence, when selenium was present in the molecule. Photoisomerization, one of the dominant deactivation pathways in the sulfur- or oxygen-containing analogues, was completely absent in the selenium-containing derivatives. Efficient triplet state formation was observed for selenium-containing derivatives incorporated into L1210 cells by diffuse reflectance laser flash photolysis. Cytotoxicity studies, carried out using clonogenic assays on L1210 leukemia cells, showed a good correlation with phi T and phi delta, measured in solution. Experimental evidence provided by this paper supports a triplet state-, and probably singlet oxygen-, mediated phototoxic mechanism. Photoisomerization or singlet state mechanisms can be discounted.
Redmond
R W
RW
Wellman Laboratories of Photomedicine, Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Srichai
M B
MB
Bilitz
J M
JM
Schlomer
D D
DD
Krieg
M
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D007834:Lasers; D007939:Leukemia L1210; D051379:Mice; D010782:Photolysis; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000633:toxicity*; D011789:Quantum Theory; D012643:Selenium; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye; D012643:Selenium