Novel Seleno- and Tellurorhodamine Photosensitizers for Applications in Photodynamic Therapy and Extracorporeal Photopheresis
Hill, Jacqueline Elise
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Rhodamine dyes with an N -methyltetrahydroquinoline replacing one dialkylamino group are termed half-julolidyl rhodamines. Selenium (Se) and tellurium (Te) analogues of the half-julolidyl rhodamine dyes were synthesized as an improvement over the half-julolidyl sulfur (S) analogues for P-gp inhibition and for use as photosensitizers (PSs) in both photodynamic therapy (PDT) and extracorporeal photopheresis (ECP). The Se analogues showed longer wavelength absorption maxima, larger extinction coefficients, and larger quantum yields for the generation of singlet oxygen (Φ( 1 O 2 )) than their lighter chalcogen analogues. Phototoxicity assays were run at Roswell Park Cancer Institute to determine the efficacy of the half-julolidyl selenorhodamines as PSs. Results showed the presence of the amide/thioamide ‘switch’ in the uptake of verapamil (VER) in Colo-26 cells. The thioamide selenorhodamines had improved P-gp inhibition over the amide selenorhodamines and showed greater cytotoxic effects. The half-julolidyl selenorhodamines were also tested in human lymphocytes at Wake Forest University for selective uptake in activated T cells followed by selective depletion of the activated T cells for ECP. The results showed that the amide analogues had greater selective uptake in activated T cells than the thioamide analogues and preserved resting T cells during selective depletion studies. A murine model followed ex vivo studies, with the best performing selenorhodamine amide 9-Se-Cl as the photosensitizer. The success of the half-julolidyl selenorhodamines coupled with encouraging data from the Texas red seleno-analogues (asymmetrical, bis julolidyl, and bis half-julolidyl) led to the synthesis of the bis gem -dimethyljulolidine selenorhodamines, a combination of the half-julolidyl and julolidyl cores. These new dyes are expected to have improved photophysical properties over those of the Texas red analogues including longer wavelengths for λ max and greater values of Φ( 1 O 2 ). The novel selenorhodamine incorporating an amide moiety on the heteroaryl substituent at the 9-position of the core will be tested as an improved PS over dye 9-Se-Cl in the selective photodepletion of activated T cells for ECP. These bis gem -dimethyljulolidine selenorhodamines may also find utility in PDT, in dye sensitized solar cells, and as photoredox catalysts. Previously synthesized seleno- and tellurorhodamines in the Detty group were briefly examined as photoredox catalysts in the oxidation of 2-phenyl-1,2,3,4-tetrahydroisoquinoline to 2-phenyl-3,4-dihydroisoquinolin-1(2 H )-one. Preliminary results indicate that both the selenium and tellurium dyes containing a mesityl substituent at the 9-position of the bisdimethylamino core yield the oxidation product over a 3-h time period.