Modular synthesis of pentacyclic-fused pyranoquinoliziniums as organelle-selective fluorescent probes

Abstract

On basis of their unique chemical and photophysical properties, and excellent biological activities, quinoliziniums have been widely used in various research fields. Herein, modular synthetic strategies for efficient synthesis of novel fluorescent quinoliziniums by using one-pot and stepwise rhodium(III)-catalyzed C–H annulations were developed. In the one-pot synthesis, the reaction between 2-aryl-4-quinolones (1) and 1,2-diarylalkynes (2) proceeded in a chemo- and regioselective manner to give quinolinone-fused isoquinolines (3) and pentacyclic-fused pyranoquinoliziniums (4). The structural diversity of pentacyclic-fused pyranoquinoliziniums (4) was expanded by the stepwise synthesis from 3 and 2, allowing the strategic incorporation of electron-donating (OMe and OH) and electron-withdrawing (Cl) substituents on the top and bottom parts of the pyranoquinoliziniums (4). These newly synthesized pyranoquinoliziniums (4) exhibited tunable absorptions (455–532 nm), emissions (520–610 nm), fluorescence lifetime (0.3–5.6 ns), large Stokes shifts (up to 120 nm), and excellent fluorescence quantum yields (up to 0.73) upon adjusting the different substituents. The the unique arrangement of N and O atoms and extended π-conjugation of 4 could cause the relocation of HOMO comparing with our previous quinoliziniums. Importantly, pyranoquinoliziniums (4a-4g and 4i) targeted the mitochondria, while 4h was localized in lysosome. Due to the remarkable photophysical properties and the potential for organelle targeting of the novel class of quinoliziniums, they could be further applied for biological, chemical and material applications.