Efficient Electrochemical Microsensor for In Vivo Monitoring of H₂O₂ in PD Mouse Brain: Rational Design and Synthesis of Recognition Molecules

Abstract

Hydrogen peroxide (H2O2), 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 H2O2 in the living brain. Current natural or nanomimic enzyme-based electrochemical methods employed for the determination of H2O2 suffer from inadequate selectivity and stability, due to which the in vivo measurement of H2O2 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 H2O2. 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 H2O2 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 H2O2 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 H2O2 in Parkinson’s disease (PD) mouse brain. The average levels of H2O2 in the cortex, striatum, and hippocampus in the normal mouse and PD mouse were systematically compared for the first time.

In Vivo Electrochemical Biosensors: Recent Advances in Molecular Design, Electrode Materials, and Electrochemical Devices

“…By using electrochemically oxidized graphene oxide (EOGO) as the inner reference, this sensor was applied to measure H 2 O 2 in Parkinson's disease (PD) mouse brain. 76 , the proposed electrochemical sensor had good selectivity for various potential disturbances in the brain. Thus, the electrochemical biosensor was successfully used to monitor O 2…”

“…And the reaction products, which could also be described as redox tags, 5-(1,2-dithiolan-3-yl)- N -(4-hydroxyphen-yl)­pentanamide (DHP) derivatives, converted the electrochemical signal from inactive into active. By using electrochemically oxidized graphene oxide (EOGO) as the inner reference, this sensor was applied to measure H 2 O 2 in Parkinson’s disease (PD) mouse brain . Superoxide anion (O 2 •– ) is also a main ROS and plays a crucial role in the production of other ROS, such as, ·OH – and ·ONOO – .…”

Implantable Electrochemical Sensors for Brain Research

“…58 Luo et al designed a series of pentamidine (DBP) derivatives that could react selectively with H 2 O 2 and electroactivate the signal. 59 Potentiometric analysis, another important electrochemical analysis method, originated from glass electrodes with a pHsensitive response. However, the large size and leakiness of this electrode structure made it difficult to apply to brain research.…”

“…To investigate the role of H 2 S n and H 2 S during oxidative stress, Dong et al designed and synthesized two organic molecules, M PS‑1 and M HS‑1 , to react specifically with H 2 S n and H 2 S and generated electroactive signals . Luo et al designed a series of pentamidine (DBP) derivatives that could react selectively with H 2 O 2 and electroactivate the signal …”

An electrochemical microsensor based on a specific recognition element for the simultaneous detection of hydrogen peroxide and ascorbic acid in the live rat brain

“…UV-visible absorption, 21–23 fluorescence spectroscopy, 24–27 electrochemistry, 28–30 high-performance liquid chromatography 31–33 and electrochemical methods 34–36 are widely used for the detection of H 2 O 2 or AA. Thereinto, electrochemical methods offer significant benefits in sensitivity and simplicity, and their ease of miniaturization is particularly noteworthy.…”