Zinc Ion Fluorescent Sensors Based On Carboxamidoquinoline

Zinc is the second most abundant transition metal ion in the human body and plays an important role in various biological processes such as gene transcription, regulation of metalloenzymes, neural signal transmission, and others. The fluorescence imaging technique, which is the most effective way, is widely used for the study of Zn²⁺ in vivo. The key to successfully apply this technique is to develop appropriate fluorescent Zn²⁺ imaging reagents. Despite having many commercial Zn²⁺ sensors, people continue endeavoring to design and synthesize new ones, to find new fluorescence recognition principles, and to improve the sensitivity, selectivity, and reliability in order to satisfy various needs.In present work, a series of new carboxamidoquinoline derivatives based on the intramolecular charge transfer mechanism have been designed and synthesized. And the recognition performance for metal ions in buffer solution has been studies.Seven carboxamidoquinoline derivatives with various aliphatic amine such as 2-(2-hydroxyethoxy)ethylamine, N-(2-hydroxyethyl)ethyldiamine, bis(2-hydroxyethyl)amine, benzoazacrown ether, and others at positionαorβof the amide group, have been developed. Among them, N-(α-(2-(2-hydroxyethoxy)ethylamino)acetyl)-8-aminoquinoline (2a-l) could exhibit ratiometric fluorescent signals for Zn²⁺. After forming the 1:1 complex between 2a-1 and Zn²⁺, there are about an 8-fold increase in fluorescence quantum yield and a 75 nm red-shift of fluorescence emission. And an obviously color change from blue-purple to blue-green emission of the solution could easily be observed by the naked eye. Moreover, 2a-1 could enter living cells and signal the presence of Zn²⁺.Eleven fluorescent sensors with different substituents such as methyl, cayno, methoxyl, N-morpholinyl, and others at position 2 or 4 of the quinoline ring of 2a-l, have been synthesized. The results indicate that the Zn²⁺-binding stability of carboxamidoquinoline could be decreased by the steric hindrance effect of 2-substituents. And the highest sensitivity to Zn²⁺ of carboxamidoquinoline could be observed by introducing 4-substituents. With increasing the electron-donating intensity of substituents at position 2 or 4 of the quinoline ring, the red-shifted emission wavelength of carboxamidoquinoline induced by Zn²⁺ is gradually decreased until fluorescence signals are transformed from the dual-wavelength ratiometric changes to the single-wavelength intensity ones. Among them, 3a-7 and 4a-4 with the N-morpholinyl group show linear, stoichiometrical, and enhanced fluorescence response to Zn²⁺ without background fluorescence. There are about 141 and 239-fold enhancement in fluorescence quantum yield, respectively. ¹H-NMR titration studies indicate the deprotonation of the amide group by coordinated Zn²⁺ and the formation of the 1:1 complex between 4a-4 and Zn²⁺.The influence on the detection performance of carboxamidoquinoline in surfactant micelle has been studies. In SDS micelle solution, the selectivity of 2a-1 could be improved in comparison with that of in conventional solution. 2a-1 shows the uniquely ratiometric Zn²⁺ identification. And the recognizing Zn²⁺ ranges are expanded from 1-10μM to 1-1000μM.