Efficient Electrochemical Microsensor for In Vivo Monitoring of H 2 O 2 in PD Mouse Brain: Rational Design and Synthesis of Recognition Molecules.

Hydrogen peroxide (H 2 O 2 ), one of the most stable and abundant reactive oxygen species (ROS), acting as a modulator of dopaminergic signaling, has been intimately implicated in Parkinson's disease, creating a critical need for the selective quantification of H 2 O 2 in the living brain. Current natural or nanomimic enzyme-based electrochemical methods employed for the determination of H 2 O 2 suffer from inadequate selectivity and stability, due to which the in vivo measurement of H 2 O 2 in the living brain remains a challenge. Herein, a series of 5-(1,2-dithiolan-3-yl)- N -(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanamide (DBP) derivatives were designed by tuning the substitute groups and sites of a boric acid ester, which served as probes to specifically react with H 2 O 2 . Consequently, the reaction products, 5-(1,2-dithiolan-3-yl)- N -(4-hydroxyphen-yl)pentanamide (DHP) derivatives, converted the electrochemical signal from inactive into active. After systematically evaluating their performances, 5-(1,2-dithiolan-3-yl)- N -(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pentanamide ( o -Cl-DBP) was finally identified as the optimized probe for H 2 O 2 detection as it revealed the fastest reaction time, the largest current density, and the most negative potential. In addition, electrochemically oxidized graphene oxide (EOGO) was utilized to produce a stable inner reference. The designed electrochemical microsensor provided a ratiometric strategy for real-time tracking of H 2 O 2 in a linear range of 0.5-600 μM with high selectivity and accuracy. Eventually, the efficient electrochemical microsensor was successfully applied to the measurement of H 2 O 2 in Parkinson's disease (PD) mouse brain. The average levels of H 2 O 2 in the cortex, striatum, and hippocampus in the normal mouse and PD mouse were systematically compared for the first time.