Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

Abstract

Novel caged nitroxides (nitroxide donors) with near-infrared two-photon (TP) responsive character, 2,2,6,6-tetramethyl-1-(1-(2-(4-nitrophenyl)benzofuran-6-yl)ethoxy)piperidine (2a) and its regioisomer 2b, were designed and synthesized. The one-photon (OP) (365 ± 10 nm) and TP (710–760 nm) triggered release (i.e., uncaging) of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical under air atmosphere were discovered. The quantum yields for the release of the TEMPO radical were 2.5% (2a) and 0.8% (2b) in benzene at ≈1% conversion of 2, and 13.1% (2a) and 12.8% (2b) in DMSO at ≈1% conversion of 2. The TP uncaging efficiencies were determined to be 1.1 GM at 740 nm for 2a and 0.22 GM at 730 nm for 2b in benzene. The cytocidal effect of compound 2a on lung cancer cells under photolysis conditions was also assessed to test the efficacy as anticancer agents. In a medium containing 100 μg mL−1 of 2a exposed to light, the number of living cells decreased significantly compared to the unexposed counterparts (65.8% vs 85.5%).

Keywords

• caged compound
• nitroxide
• photolysis
• radical
• theranostics
• two-photon