Cationic dyes are photosensitizers for the photodynamic therapy of cancer.¹ Chalcogenopyrylium dyes (E = O, S, Se, Te) have demonstrated particular selectivity for the mitochondria of cancer cells.^1,2 An undergraduate researcher would prepare a library of chalcogenopyrylium dyes 3 by condensation of a 4-methyl-2,6-disubstituted chalcogenopyrylium dye with a commercially available, aromatic aldehyde 2 by heating the two components in acetic anhydride.^2,3 The dyes 3 can be isolated by crystallization/recrystallization or by extraction/crystallization to give purified products. The counterion associated with the cationic dye can be varied using ion exchange resins.

The student would characterize the library of compounds by NMR spectroscopy, mass spectrometry, and UV/visible/near infrared spectrophotometry and would obtain elemental analyses for new, crystalline derivatives.

After a library of 6-10 compounds was prepared, the library would be screened for photochemical activity in vitro against R3230AC rat mammary adenocarcinoma cells or Colo-26 mouse colon cancer cells at Roswell Park Cancer Institutes in the labs of Dr. Sandra Gollnick or Dr. Allan Oseroff with the assistance of the undergraduate researcher. A correlation of chemical structure with biological activity would then be made.

References:

1. Detty, M.R., S.L. Gibson and S. Wagner (2004). "Current Clinical and Pre-Clinical Photosensitizers for use in Photodynamic Therapy." J. Med. Chem. 47:ASAP.
2. Detty, M.R., P.B. Merkel, R. Hilf, S.L. Gibson and S.K. Powers (1990). "Chalcogenapyryliu7m Dyes as Potential Photochemotherapeutic Agents. II. Mitochondrial Targetting and Inhibition of Cytochrome c Oxidase in Isolated Mitochondrial Suspensions." J. Med. Chem. 33:1108-1115.
3. Detty, M.R. and B. J. Murray (1982). "Telluropyrylium Dyes. 1. 2,6-Diphenyltelluropyrylium Dyes." J. Org. Chem. 47: 5235-5240.