Accurate Construction of NIR Probe for Visualizing HClO Fluctuations in Type I, Type II Diabetes and Diabetic Liver Disease Assisted by Theoretical Calculation.

Hypochlorous acid (HClO) is a key signaling molecule which involved in various pathological and physiological processes and the immune system. It had been proved that excess HClO in the organisms was closely associated with diabetes. In this paper, we constructed a series of BODIPY-based fluorophores modified with olefinic bond. With the assistance of theoretical calculations, the optimized near-infrared (NIR) dye BDP-ENE-S-Me, which possessed the longest wavelength (690 nm) and the best stability, was screened and synthesized. Based on BDP-ENE-S-Me, we further introduced N, N-dimethylcarbamate group to construct a NIR fluorescent probe BDP-ENE-ClO. BDP-ENE-ClO displayed excellent selectivity and sensitivity with a low detection limit (49 nM) towards HClO. Besides, the probe was successfully applied in monitoring concentration fluctuations of HClO in vitro and in vivo caused by various stimuli. Most importantly, the over-production of HClO in the type I, type II diabetes and diabetic liver disease mice models could be visualized and assessed precisely with the assistance of BDP-ENE-ClO. By comparing fluorescent intensity of diabetic mice models with that of diabetic liver disease mice models, the probe was competent to assess the progression of diabetes.