Within her SONATINA grant, Magda is conducting research on a new potential therapeutic molecule: TDMQ20. In our previous posts, we described her electrochemical studies, which helped better understand the redox properties of TDMQ20 itself and its complexes with copper ions (Cu(II)).
The next stage of the project focused on investigating the extent to which TDMQ20 can remove copper ions from the Cu–β-amyloid(1–16) complex.1 This question is important because these complexes are considered harmful to the organism and are associated with the development of Alzheimer’s disease.
Dr Małgorzata Wesoły from Warsaw University of Technology collaborated with Magda to support the study with multivariate data analysis. She applied advanced chemometric tools, including Principal Component Analysis (PCA) and Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) to voltammetric signals. Chemometric methods provided valuable insight into the mechanism of copper binding competition between Aβ(1–16)complex, and TDMQ20. Part of this work was carried out during her research visit in the group of Prof. José Manuel Amigo Rubio at the Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country.
Extensive research over recent decades has shown that β-amyloid (Aβ) peptides and their aggregation play a key role in the development of Alzheimer’s disease. These peptides can bind copper ions (Cu(II)), and the resulting complexes accelerate aggregation and promote the formation of reactive oxygen species (ROS), which damage neurons through oxidative stress.
For this reason, increasing attention is being paid to compounds capable of chelating copper ions and removing them from amyloid complexes. Among such compounds are 8-aminoquinoline derivatives, known as TDMQ molecules. In this study, we investigated whether the new compound TDMQ20 can effectively compete with the Aβ(1–16) peptide for Cu(II) ions.
The results demonstrate that TDMQ20 can bind copper ions even in the presence of β-amyloids. Moreover, chemometric analysis using the MCR-ALS method allowed the researchers to determine the individual contributions of components in the studied samples. The results clearly show that TDMQ20 is capable of completely extracting Cu(II) ions from the Aβ(1–16)–Cu(II) complex, forming a stable TDMQ20–Cu(II) complex.
This work demonstrates that combining electrochemical techniques with chemometric analysis is an effective approach for testing potential drugs that chelate copper ions. Such compounds are of interest for the treatment of neurodegenerative diseases, including Alzheimer’s disease, as well as Huntington’s disease and Wilson’s disease.
- M. Z. Wiloch-Szyborska, N. Baran, G. Gorla, J. M. Amigo, M. Wesoły
Investigation of copper binding competition between a potential anti-Alzheimer’s drug and Aβ(1–16) based on voltametric and chemometric analysis, Electrochim. Acta. 562, 148716 (2026). (link)
