I Synthesis and pharmacological activity of novel rhodamine analogues; II Controlled aggregation of rhodamine analogues on thin-films
Gannon, Michael Kim, II
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The interesting biological and physical properties of TMR-S and TMR-Se has lead to the design and synthesis of a series of rhodamine and rosamine derivatives with structural diversity in the heteratom of the xanthylium core, the amino substituent of the 3-position, and the aryl or heteroaryl group at the 9-position. Deprotonation and lithium-bromide exchange reactions have been developed to give heavy-atom analogues of rhodamine that introduce the carboxylic acid oxidation state into the 9-aryl or heteraryl substituent (carboxylic acid, primary carboxamide, ester, tertiary amide, or tertiary thioamide) (Chapter 2). Rosamine analogues that lack the carboxylic acids state also have been synthesized via the addition Grignard or organolithium reagents to chalcogenoxanthone precursors (Chapter 2). Notably, the syntheses of several rhodamine and rosamine analogues that incorporate Te for O in the xanthylium core have been described (Chapter 2). These compounds were evaluated for affinity and ATPase stimulation in MDR3 CL P-gp as well as in wild-type human P-gp, for their ability to be transported in multidrug-resistant cells, and for their ability to inhibit/modulate P-gp in multidrug-resistant cells (Chapter 4). Structural features were identified that gave high affinity for P-gp with limited stimulation of ATPase activity in isolated protein and inhibited/modulated P-gp in multidrug-resistant cells to increase uptake of calcein AM (CAM) and vinblastine (VIN) (Chapter 4). The photophysical properties were characterized for the pentacyclic thio- and selenoxanthylium analogues as well as the measured uptake of the pentacylic thioxanthylium analogue between chemosensitive AUXB1 and drug-resistant CR1R12 cells (Chapter 4). These analogues were also examined for their ability to function as photosensitizers for chemosensitive AUXB1 and drug-resistant CR1R12 cells (Chapter 4). The DNA binding efficacy of several rhodamine and rosamine derivatives were investigated by the non-spectrophotometric methods of isothermal titration calorimetry (ITC) and a topoisomerase I DNA unwinding assay (Topo I assay) (Chapter 5). The photophysical properties were characterized for the structurally similar, yet flexible, chalcogenopyrylium dyes in solution and in solution bound to DNA. While the photoinactivation of the pseudo-rabies virus upon treatment of red blood cell suspensions with dyes and light were examined, the photodamage of DNA in dye-DNA complexes were measured using pUC19 DNA in the presence of dye at different light doses (Chapter 5). Several rhodamine dyes were characterized as sensitizers of nanocrystalline titania dye-sensitized solar cells (DSSC's) (Chapter 6). The maximum incident photon-to-current efficiencies (IPCEs) for each dye were determined.