Study Of New BODIPY-based Fluorescent Chemodosimeters For Cu²⁺ And Their Performance In Cellular Imaging

As the third-most-abundant transition metal in the human body, copper ion plays a critical role to maintain and regulate the normal metabolism of the whole system. However, excessive levels of copper could bring a lot of diseases to organisms, such as Wilson’s diseases, Alzheimer’s disease, familial amyotrophic lateral sclerosis, Parkinson’s and so on.In the past few years, more and more Cu2+fluorescent probes have been reported based on different detection mechanisms, in which reaction-based Cu2+probes have attracted intense attention. However, many of these suffer from the limits such as act only in pure organic solvents or solutions, with very small amounts of water, require specific reaction conditions or show low Cu2+selectivity in the presence of other metal ions. Thus, it is still of great interest to develop new fluorescent probes for Cu2+with high selectivity and sensitivity.In this article, we designed and synthesized three BODIPY-based compounds:M1、M2and M3. In aqueous acetonitrile solution, compounds M2and M3can both recongnize Cu2+without being interferenced by other metal ions (Li+,Na+,K+, Mg2+, Ca2+, Ba2+, Al3+, Pb2+, Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu+, Ag+,Zn2+, Cd2+, Hg2+) and common anions (Cl-, SO42-, NC3-, OAc-, Br-) and also have high sensitivity for Cu2+. The detection limit of M2and M3to Cu2+are0.2μM and0.1μM, respectively. Upon the addition of Cu2+for a period, the colour of the M2or M3solution has a significant change and the fluorescence enhancement of M2and M3are ca.1340-fold and298-fold, respectively. M2and M3are pH-insensitive Cu2+probes, which have a wide rang of pH to detect Cu2+, including the physiological pH. Through the confocal imaging study in Hela cells, we confirmed that M2and M3can be widely used for detecting Cu2+in the area of bioimaging. However, the compound M1can not recongnize any metal ions, thus it can’t be used as a fluorescence probe.In addition, we also studied the sensing mechanism of such fluorescent probs by1H NMR spectral titration, we finally proposed the mechanism that Cu2+firstly coordinated with the probe molecules and then promoted the hydrolysis of unsaturated CH=N bond in hydrazones.