Theoretical studies for the development of detection mechanisms for tamoxifen and derivative metabolites

Abstract

Tamoxifen is an estrogen receptor antagonist designated as the main therapy for treating and preventing breast cancer, which has been identified as a major public health concern. Identifying and quantifying tamoxifen and its main by-products in blood serum are essential indicators to predict the treatment evolution and prospective success rate. The gold standard of such quantification is based on spectrometry and chromatography techniques. However, since they are highly specialized and centralized techniques, they are not accessible to entire public clinical and health areas. Alternatives to current standards to assess tamoxifen therapy have been identified as an important need. Therefore, this work is aimed to provide an identification and detection mechanism to inspire the development of nanosensors with the ability to differentiate and quantify tamoxifen and its main derivatives. This goal is challenging since tamoxifen, and its metabolites share their chemical composition and conformational arrangement to a great extent. This work addresses the problem from a theoretical perspective, applying computational chemistry tools within the molecular electronics framework. We focused on finding differentiation parameters based on the fundamental charge transport properties when tamoxifen and derivatives are implemented as the central molecule of a single molecular junction. We applied the density functional theory (DFT) to characterize individual molecules as isolated systems. The charge transport calculations were implemented using density functional theory with the non-equilibrium Green’s functions (DFT-NEGF). We explored the rectification and bistable switching behavior of different systems, including tamoxifen and derivatives, to develop dual-task molecular devices that, besides pure electronics performance, have parallel sensing applications. We expect that the resultant differentiation mechanism of this thesis project will inspire the development of new technologies that can ease the monitoring of tamoxifen treatments for all.