Single molecule conductance spectroscopy: probing the gold-bio interface at the atomic scale
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Abstract
This thesis uses single molecule conductance spectroscopy to probe the binding mechanisms and conductance characteristics of various biologically relevant molecules with gold at the atomic level. Firstly, we identify imidazole as a pH-activated linker for forming stable single gold molecule junctions, which present several distinct configurations and reproducible electrical characteristics. We then examine the resulting conductance signatures and identify corresponding binding geometries, which involve up to four imidazole molecules binding in the junction in parallel. In addition, we discover the distinct conductance signatures that indicate the in-situ formation of molecule-metal-molecule chains within the molecular junction. Building on this foundation, the investigation continues into the origin of the conductance enhancement observed in benzimidazole dimers compared to imidazole dimers. Density Functional Theory (DFT) calculations reveal that the parallel stacking of two benzimidazoles, due to the large π system between electrodes, represents the most energetically favorable configuration, leading to dimer conductance enhancement. The smaller size and greater conformational freedom of imidazole enable it to access a variety of stacking angles. Having understood the underlying mechanism, we use substituents to promote the cooperative in situ assembly of imidazole derivatives into a parallel binding configuration, subsequently enhancing conductance. Next, we shift our focus to adenine, one of the most important biological building blocks of deoxyribonucleic acid (DNA). By using structurally similar molecules, we can assign different conductance signals to various binding configurations of adenine. This approach also enables the differentiation between adenine and its biological derivatives, 2’deoxyadenosine and 6-methyladenine. Using single molecule conductance signals, we demonstrate the potential of single molecule conductance spectroscopy as a biosensing platform. Finally, we present a detailed study of the pH-activated intramolecular conductance features of histamine. By employing histamine and its derivatives, we associate different conductance features with specific binding sites. DFT calculation is used to simulate the different ethylamine configurations of histamine in molecular junctions, and flicker noise analysis is applied to identify and assign one of the conductance features to a hydrogen bond-assisted binding configuration. These results and insights collectively establish single molecule conductance spectroscopy as a robust platform for studying complex gold-biomolecule interactions.
Description
2024