Quantum electroanalysis in drug discovery

Abstract

Recent discoveries in quantum electrochemistry have shown that in electrolytic media, both electron transport (in molecular electronics) and electron transfer (in electrochemical reactions) are driven by common quantum electrodynamics (QED) principles. Consequently, the electronic structures of exemplary man-made interfaces incorporating organic semiconductors, quantum dots, graphene, and redox dynamics within peptide structures can be accessed in an in situ and real-time manner at room temperature under physiological conditions. This is made possible by the fact that the above components are governed by QED principles within the framework of quantum-rate theory. Thus, quantum electroanalysis (QEA) techniques can be developed through the modification of these interfaces with molecular receptors. Upon subsequent ligand binding, the signal associated with the electronic structure of the interface is shifted in a sensitive manner. With the above considerations in mind, this study reviews the ability of redox-tagged peptides and graphene monolayers to quantify binding affinity constants as key parameters in the drug discovery process. More specifically, these constants are essential for determining the free energy of binding. The advantages of these QED signals over optical signals (e.g., surface plasmon resonance) are demonstrated, wherein the attomolar-level sensitivities permit more accurate measurement of the binding affinities of low-molecular-weight ligand–receptor pairs (e.g., metabolites), in addition to providing binding information under dilute conditions. The miniaturisation of both the plate wells and the readout electronics constitutes additional cost-effective advantages of QEA over traditional optical technologies.