Highly Selective and Efficient Synthesis of 7-Aminoquinolines and Their Applications as Golgi-Localized Probes.

Abstract

Quinoline derivatives have extensively been used for both pharmaceutical agents and bioimaging. However, typical synthesis of quinoline derivatives is generally through strong acid/base-catalyzed or metal-catalyzed methods at high temperatures. Here we report a catalyst-free synthesis of 2,4-disubstituted 7-aminoquinolines with high selectivity and good yields via the introduction of a trifluoromethyl group. It is discovered that quinolines containing both amino and trifluoromethyl groups exhibit strong intramolecular charge-transfer fluorescence with large Stokes shifts. We further applied the obtained quinolines to live-cell imaging and found that some of the derivatives can target specifically Golgi apparatus in various cell lines (HeLa, U2OS, and 4T1 cells) in vitro and the colocalization with commercial Golgi marker is retained during the mitosis in HeLa cells. Moreover, the quinoline dyes can also be used for Golgi apparatus imaging with two-photon fluorescence microscopy. These results provide new insights into developing low cost Golgi-localized probes.