Molecular PhotoswitchesTowards the Rational design of Donor-Acceptor Stenhouse Adducts and Photoswitchable Transmembrane Peptides stars

Abstract

This thesis focuses on improving the photochromic properties of donor-acceptor Stenhouse adducts (DASAs) and achieving optical control of transmembrane peptides using azobenzene-based cross-linkers. Specifically, the present thesis is divided into seven main chapters. The first chapter provides a historical introduction to organic photochemistry and, more specifically, to photochromism. The second chapter motivates the work performed in this thesis by reviewing previous studies related to DASAs and surveying the most relevant literature on the use of azobenzenes to achieve peptide photocontrol. Therefore, this review is intended to serve as a reference for the subsequent chapters. Against the background previously described, the third chapter outlines the research goal and objectives of this work. The fourth chapter is focused on red-shifting the activation wavelengths of DASAs by rationally replacing oxygen with sulfur atoms. Following this approach, a new family of DASAs sensitive to wavelengths within the therapeutic window is designed. Besides, the photochromic properties of four selected candidates are studied via time-resolved absorption spectroscopy to evaluate their potential application. In the fifth chapter, photocontrol of the membrane topology of an α-helical peptide is achieved for the first time by incorporating an azobenzenebased cross-linker in its structure. The light-induced transmembrane/interface transition undergone by the peptide is characterized by infrared spectroscopy. In addition, future directions of this research line are discussed. The sixth chapter presents a brief summary of the work done during my short-term research stay in the Szymański Lab at the University of Groningen (The Netherlands). In particular, this chapter describes the synthesis of previously inaccessible water-soluble and visible lightcontrolled azobenzenes. Finally, the seventh chapter draws together the conclusions from the previous chapters and highlights their significance to the field of study.