Highly Stable Electrochemical Probe with Bidentate Thiols for Ratiometric Monitoring of Endogenous Polysulfide in Living Mouse Brains

The lack of reliable approaches for real-time measurement and quantification of polysulfides (H2Sn) in vivo greatly limits the exploration of their potential roles in brain functions. Herein, an electrochemical probe, 4-(5-(1,2-dithiolan-3-yl)pentanamido)-1,2-phenylene bis(2-fluoro-5-nitrobenzoate) (FP2), was rationally designed and created for determination of H2Sn. The bis-electrophilic groups of FP2 could specifically recognize two -SH groups in H2Sn and trigger the generation of an electroactive pyrocatechol moiety, resulting in a well-defined faradic current signal at similar to 0.24 V (vs Ag/AgCl). Meanwhile, bidentate thiols were designed as anchoring sites to greatly improve the assembled stability of FP2 at the Au surface, which efficiently defended the interference of glutathione (GSH) with a current decrease of less than 5.2% even after long-term measurements in 5 mM GSH for 3 h. In addition, a stable inner reference molecule with dithiols, alpha-lipoic acid ferrocenylamide (FcBT), was synthesized to construct a ratiometric electrochemical strategy for in vivo determination of H2Sn through one-step coassembling with FP2 via double S-Au bonds. The present ratiometric strategy demonstrated high selectivity for real-time tracking of H2Sn in a linear range of 0.25-20 mu M. Eventually, the developed microelectrode with high selectivity, accuracy, and stability was employed for in vivo assaying of H2Sn in mouse brains with ischemia.

Automated summary

A lack of reliable approaches for real-time measurement and quantification of polysulfides in vivo has limited exploration of their roles in brain functions. In this study, an electrochemical probe was designed for determination of H2Sn, showing high selectivity for real-time tracking in a linear range of 0.25-20 μM. The developed microelectrode with high selectivity, accuracy, and stability was successfully employed for in vivo assaying of H2Sn in mouse brains with ischemia.