Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications
Category of Work
Article
Publication Title
JBIC Journal of Biological Inorganic Chemistry
Abstract
There is currently an unmet demand for multi-functional precision treatments for Alzheimer's disease (AD) after several failed attempts at designing drugs based on the amyloid hypothesis. The focus of this work is to investigate sulfur-bridged quinoline ligands that could potentially be used in chelation therapies for a subpopulation of AD patients presenting with an overload of labile copper ions, which are known to catalyze the production of reactive oxygen species (ROS) and exacerbate other markers of AD progression. The ligands 1-(2′-thiopyridyl)isoquinoline (1TPIQ) and 2-(2′-thiopyridyl)quinoline (2TPQ) were synthesized and characterized before being electrochemically investigated in the presence of diferent oxidizing and reducing agents in solution with a physiological pH relevant to the brain. The electrochemical response of each compound with copper was studied by employing both hydrogen peroxide (H2O2) as an oxidizing agent and ascorbic acid (AA) as an antioxidant during analysis using cyclic voltammetry (CV). The cyclic voltammograms of each quinoline were compared with similar ligands that contained aromatic N-donor groups but no sulfur groups to provide relative electrochemical properties of each complex in solution. In a dose-dependent manner, it was observed that AA exerted dual-efcacy when combined with these chelating ligands: promoting synergistic metal binding while also scavenging harmful ROS, suggesting AA is an efective adjuvant therapeutic agent. Overall, this study shows how coordination by sulfur-bridged quinoline ligands can alter copper electrochemistry in the presence of AA to limit ROS production in solution.
First Page
643
Last Page
653
DOI
https://doi.org/10.1007/s00775-023-02013-1
Publication Date
8-18-2023
Recommended Citation
Crnich, Emma; Sanchez, Erik; Havens, Mallory A.; and Kissel, Daniel S., "Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications" (2023). Biology Department Faculty Articles. 15.
https://digitalcommons.lewisu.edu/biology_facpubs/15
