Here, we present combined experimental and theoretical studies on the spectroelectrochemical properties of 8-aminoquinoline (8AQ). 8AQ is a model molecule for drugs that can chelate copper(II) ions, and thus it may find applications in halting the development of Alzheimer’s disease.Although over a hundred years have passed since Alzheimer’s disease (AD) was first described, it remains incurable to this day. According to one of the leading hypotheses, peptides from the β-amyloid (Aβ) group are responsible for the development of AD. By binding copper(II) ions, Aβs form complexes whose presence promotes the formation of harmful, highly active compounds called reactive oxygen species (ROS) and reactive nitrogen species (RNS). In a series of recent studies, we investigated the differences in electrochemical properties of Cu(II)-complexes with the amyloids Aβ(11-16) and Aβ(3-16) with their pyroglutamated versions, pAβ(11-16) and pAβ(3-16). [1,2] These results showed that the pyroglutamate amyloids are conducive to Cu(II)-reduction at a potential associated with ROS production. Given the abundance of pyroglutamated amyloids in senile plaques, this could have important consequences for AD pathophysiology. Overproduction of ROS and RNS can cause neuron death. Therefore, substances that can aid in removing copper(II) ions from β-amyloids could block the formation of ROS and RNS. Recently, a new quinoline derivative with unique properties has undergone preclinical studies. However, little is known about the redox properties of such molecules, which may be crucial in the early stages of testing potential therapeutic substances.Therefore, we aimed to perform electrochemical and spectroelectrochemical studies of a model molecule, 8-aminoquinoline, whose redox properties were not yet well characterized To fully characterize both anodic and cathodic processes, we used cyclic and pulse voltammetry over a wide range of pH values, including physiological (pH=7.4). In addition, the experimental results were supported by DFT-based computational studies exploring the energy landscapes of the possible reactions and advancing understanding of the electrochemical phenomena.The kind of electrochemical tests presented here may prove of crucial importance for the development of more effective drugs against AD. The high failure rate and relatively poor performance of the recently approved treatment indicates the need to extend preclinical studies with new, so far unused techniques, allowing a more complete picture to be obtained of the effectiveness and toxicity of the potential drug candidates.[1] M.Z. Wiloch, N. Baran, M. Jönsson‐Niedziółka, The Influence of Coordination Mode on the Redox Properties of Copper Complexes with Aβ(3‐16) and Its Pyroglutamate Counterpart pAβ(3‐16), ChemElectroChem. 9 (2022). https://doi.org/10.1002/celc.202200623.[2] M.Z. Wiloch, M. Jönsson-Niedziółka, Very small changes in the peptide sequence alter the redox properties of Aβ(11–16)-Cu(II) and pAβ(11–16)-Cu(II) β-amyloid complexes, Journal of Electroanalytical Chemistry. 922 (2022) 116746. https://doi.org/10.1016/j.jelechem.2022.116746.
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