Analogues of Texas red incorporating the heavy chalcogens S, Se, and Te atoms in the xanthylium core were prepared from the addition of aryl Grignard reagents to appropriate chalcogenoxanthone precursors. The xanthones were prepared via directed metalation of amide precursors, addition of dichalcogenide electrophiles, and electrophilic cyclization of the resulting chalcogenides with phosphorus oxychloride and triethylamine. The Texas red analogues incorporate two fused julolidine rings containing the rhodamine nitrogen atoms. Analogues containing two “half-julolidine” groups (a trimethyltetrahydroquinoline) and one julolidine and one “half-julolidine” were also prepared. The photophysics of the Texas red analogues were examined. The S-analogues were highly fluorescent, the Se-analogues generated single oxygen (1O2) efficiently upon irradiation, and the Te-analogues were easily oxidized to rhodamines with the telluroxide oxidation state. The tellurorhodamine telluroxides absorb at wavelengths ≥690 nm and emit with fluorescence maxima >720 nm. A mesityl-substituted tellurorhodamine derivative localized in the mitochondria of Colo-26 cells (a murine colon carcinoma cell line) and was oxidized in vitro to the fluorescent telluroxide.

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin.

Aerobic oxidation of thiols to disulfides was achieved photocatalytically using a tellurorhodamine chromophore (9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate) as both the sensitizer and catalyst. The proposed mechanism, supported experimentally and computationally with DFT, involves the formation of a tellurorhodamine telluroxide from reaction with water and singlet oxygen generated by irradiation of the tellurorhodamine. The oxidation to the telluroxide is accompanied by the formation of hydrogen peroxide. The telluroxide oxidizes thiols to regenerate the tellurorhodamine and the disulfide plus water. Mechanistically, DFT suggests adding two thiols to the telluroxide with the loss of H2O to give a trigonal-bipyramidal Te(IV), which undergoes concerted loss of disulfide to regenerate 1. Oxidation of thiophenol and 2-naphthalenethiol was complete after 2 h of irradiation with visible light under atmospheric conditions. Oxidation of the electron-poor 2,6-dichlorothiophenol, the sterically bulky tert-butylmercaptan, and aliphatic dodecanethiol was slower. The two aliphatic thiols displayed competing catalyst degradation. The corresponding selenorhodamine chromophore (9-mesityl-3,6-bis(dimethylamino)selenoxanthylium hexafluorophosphate) does not form the corresponding selenoxide under similar conditions and photooxidizes thiophenol and 2-naphthalenethiol much more slowly (≤6% conversion after 2–3 h).

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Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M).