Tailoring Oxygen-Containing Groups on Graphene for Ratiometric Electrochemical Measurements of Ascorbic Acid in Living Subacute Parkinson's Disease Mouse Brains

Ascorbic acid (AA), a major antioxidant in the central nervous system (CNS), is involved in withstanding oxidative stress that plays a significant role in the pathogenesis of Parkinson's disease (PD). Exploring the AA disturbance in the process of PD is of great value in understanding the molecular mechanism of PD. Herein, by virtue of a carbon fiber electrode (CFE) as a matric electrode, a three-step electrochemical process for tailoring oxygen-containing groups on graphene was well designed: potentiostatic deposition was carried out to fabricate graphene oxide on CFE, electrochemical reduction that assisted in removing the epoxy groups accelerated the electron transfer kinetics of AA oxidation, and electrochemical oxidation that increased the content of the carbonyl group (C═O) generated an inner-reference signal. The mechanism was solidified by ab initio calculations by comparing AA absorption on defected models of graphene functionalized with different oxygen groups including carboxyl, hydroxyl, epoxy, and carbonyl. It was found that epoxy groups would hinder the physical absorption of AA onto graphene, while other functional groups would be beneficial to it. Biocompatible polyethylenedioxythiophene (PEDOT) was further rationally assembled to improve the antifouling property of graphene. As a result, a new platform for ratiometric electrochemical measurements of AA with high sensitivity, excellent selectivity, and reproducibility was established. In vivo determination of AA levels in different regions of living mouse brains by the proposed method demonstrated that AA decreased remarkably in the hippocampus and cortex of a subacute PD mouse than those of a normal mouse.