Design and synthesis of diarylethene photoswitches: from photochemical properties to switchable fluorescence and photopharmacology

Thesis

This thesis presents an investigation into diarylethene-based organic photoswitches, with emphasis on optimizing their photoswitching capabilities. The research then progresses to implement these enhanced photoswitches in practical applications, specifically focusing on switchable fluorescence systems and photopharmacology.

Chapter 1 provides a review of molecular photoswitch research, elucidating fundamental models, quantitative formalisms, and key photoswitching performance parameters. A comparative analysis of various photoswitch classes is presented, highlighting their structural and photochemical features. This analysis identifies diarylethenes as a promising class of photoswitch for further optimization.

Chapter 2 describes the synthesis and characterization of push-push, pull-pull, and push-pull diarylethenes with varying lengths of conjugation. A comprehensive examination of their photophysical and photochemical properties is presented, with observed trends rationalized through DFT and TD-DFT calculations, and conformational sampling. The chapter culminates in the identification of a water-soluble diarylethene, featuring two N-methylpyridinium groups with alkyne spacers, capable of bidirectional visible light photoswitching with quantitative photostationary state distribution.

Chapter 3 extends the findings of Chapter 2, utilizing the optimized diarylethene to develop two photoswitchable fluorophores based on a diarylethene-cyanine dyad design. The diarylethene functions as a photocontrollable switch for the fluorophore, enabling reversible transitions between fluorescent and non-fluorescent states. The chapter details the synthesis of these photoswitchable dyads and provides an in-depth characterization of their fluorescence switching properties and fatigue resistance.

Chapter 4 explores diarylethenes as photoswitchable ligands targeting G-quadruplexes. The synthesis of four diarylethene-based switchable ligands is outlined, followed by an examination of their binding interactions with G-quadruplexes. This chapter reveals that the open and closed isomers of the diarylethenes exhibit distinct affinities for G-quadruplexes and varying degrees of cytotoxicity.

Chapter 5 summarizes the key findings of the research and provides a critical outlook for future investigations in this field.

Authors: Qiu, S

• DOI: 10.5287/ora-dq2bvydxy
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: switchable fluorophore; photoswitchable ligand; photoswitch; dithienylethene; diarylethene; photopharmacology
• Subjects: Organic chemistry; Chemistry; Photochemistry