Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201, P. R. China.
Anal Chem. 2021 Dec 14;93(49):16598-16607. doi: 10.1021/acs.analchem.1c03965. Epub 2021 Nov 29.
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 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. 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.
抗坏血酸（AA）是中枢神经系统（CNS）中的一种主要抗氧化剂，可抵抗氧化应激，在帕金森病（PD）的发病机制中起着重要作用。探索 PD 过程中 AA 的紊乱对于理解 PD 的分子机制具有重要意义。在此，通过碳纤维电极（CFE）作为基质电极，设计了一个三步电化学过程来定制石墨烯上的含氧基团：恒电位沉积在 CFE 上制备氧化石墨烯，电化学还原辅助去除环氧基团，加速 AA 氧化的电子转移动力学，电化学氧化增加了羰基（C═O）的含量，产生了内部参考信号。通过比较不同含氧基团（包括羧基、羟基、环氧和羰基）功能化的石墨烯缺陷模型上 AA 的吸收，通过计算对机制进行了固化。结果表明，环氧基团会阻碍 AA 物理吸附到石墨烯上，而其他官能团则有利于其吸附。进一步合理组装生物相容性聚 3,4-乙烯二氧噻吩（PEDOT），以提高石墨烯的抗污性能。因此，建立了一种新的用于 AA 比率电化学测量的高灵敏度、高选择性和重现性的平台。该方法用于测定活鼠脑不同区域的 AA 水平，结果表明，与正常鼠相比，亚急性 PD 鼠海马和皮层中的 AA 显著降低。
