A Unique Approach to Development of Near-Infrared Fluorescent Sensors for in Vivo Imaging

摘要

Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for imaging biomole- cules in living systems. However, NIR fluorescent sensors are very challenging to be developed. Herein, we describe the discovery of a new class of NIR fluorescent dyes represented by 1a/1c/1e, which are superior to the traditional 7- hydroxycoumarin and fluorescein with both absorption and emission in the NIR region while retaining an optically tunable hydroxyl group. Quantum chemical calculations with the B3LYP exchange functional employing 6-31G(d) basis sets provide insights into the optical property distinctions between la/lc/le and their alkoxy derivatives. The unique optical properties of the new type of fluorescent dyes can be exploited as a useful strategy for development of NIR fluorescent sensors. Employing this strategy, two different types of NIR fluorescent sensors, NIR-H_2O_2 and NIR-thiol, for H_2O_2 and thiols, respectively, were constructed. These novel sensors respond to H_2O_2 or thiols with a large turn-on NIR fluorescence signal upon excitation in the NIR region. Furthermore, NIR-H_2O_2 and NIR-thiol are capable of imaging endogenously produced H_2O_2 and thiols, respectively, not only in living cells but also in living mice, demonstrating the value of the new NIR fluorescent sensor design strategy. The new type of NIR dyes presented herein may open up new opportunities for the development of NIR fluorescent sensors based on the hydroxyl functionalized reactive sites for biological imaging applications in living animals.