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.

Rational Design of a Targetable Fluorescent Probe for Visualizing H2S Production under Golgi Stress Response Elicited by Monensin

“…Because of the strong electronegativity of the fluorine atom and the large bond energy of the C–F bond, not only the stability of the corresponding compound is enhanced, but also its fat solubility is improved. So it can easily enter the Golgi apparatus through the barrier of the membrane because of its lipophilicity. , Therefore, we reasonably speculate the 4-CF 3 -substituted quinoline derivatives can specifically target the Golgi apparatus . Mounting studies have demonstrated that the azido group is an excellent recognition receptor because of its easy introduction and high specificity to H 2 S. − So an azide-based fluorescent probe, Gol-H 2 S , was reasonably constructed by employing 4-CF 3 -substituted 7-aminoquinoline (compound 1 ) with a strong push–pull structure as a fluorophore.…”

“…39,40 Therefore, we reasonably speculate the 4-CF 3substituted quinoline derivatives can specifically target the Golgi apparatus. 22 Mounting studies have demonstrated that the azido group is an excellent recognition receptor because of its easy introduction and high specificity to H 2 S. 25−28 So an azide-based fluorescent probe, Gol-H 2 S, was reasonably constructed by employing 4-CF 3 -substituted 7-aminoquinoline (compound 1) with a strong push−pull structure as a fluorophore. In the synthesis of probe Gol-H 2 S, the amino group was easily modified to the azido moiety.…”

“…In recent years, because of its outstanding sensitivity, high spatial and temporal resolution, and noninvasiveness, a fluorescent probe is still an effective tool for in situ observation of important biological signal molecules. − In the past few years, there have been many excellent H 2 S probes. , For example, Fan and co-workers designed a two-photon H 2 S fluorescent probe by introducing an azido group into a near-infrared fluorophore, which is the first probe for successful visualization of H 2 S in vivo . Yu and co-workers designed a ratiometric H 2 S probe employing an azido group as recognition site of H 2 S .…”

An Integrated Fluorescent Probe for Ratiometric Detection of Glutathione in the Golgi Apparatus and Activated Organelle-Targeted Therapy

“…As for fluorophores, we chose aminoquinoline derivatives because of their outstanding Golgi-targeting capability and desirable photophysical properties. 63,64 Therefore, we synthesized the probe GT-GSH based on 4-CF 3 -7aminoquinoline for highly sensitive and selective detection of GSH (Scheme 1). The free probe GT-GSH emits blue fluorescence because the amino group is protected.…”

A Golgi-Targeting and Dual-Color “Turn-On” Probe for Spatially Precise Imaging of Furin

“…Herein, employing Förster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) principles, we designed a Golgi-targeting and dual-color “Turn-On” probe Q-RVRR-DCM for spatially precise imaging of intracellular furin, as schematically illustrated in Figure a. In our design, the quinoline dye (Q) was selected as a Golgi-targeting fluorophore, which could specifically localize in the Golgi apparatus. − Dicyanomethylene-4 H -pyran (DCM) was chosen as another fluorophore because it provides not only a large Stokes shift but also a superb fluorescent yield owing to its ultrafast ICT process. − Q and DCM were connected by the Arg-Val-Arg-Arg (RVRR) peptide linker, acting as the energy donor and acceptor in the FRET system, respectively. In Q-RVRR-DCM , Q almost does not emit fluorescence due to the FRET process from Q to DCM.…”