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Title: Novel azoheteroaryl photoswitches and their applications
Author: Weston, Claire Elizabeth
ISNI:       0000 0004 7427 6800
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Photoswitchable compounds have diverse applications, from photopharmacology to optical data storage. Azobenzenes are one of the most commonly used photoswitches, with a wealth of research focused on improving the photoconversion achieved upon irradiation and increasing the thermal stability of the Z-isomer. This work reports the development, study, and applications of the understudied azoheteroaryl photoswitches. A new class of azoheteroarenes, the arylazopyrazoles, have been developed. These photochromic compounds undergo very slow Z-E thermal isomerisation compared to the azobenzenes and achieve good to quantitative photoswitching between the two isomers. The conformation of the Z-isomers of these azoheteroarenes, and hence their spectral properties, can be tuned by altering the substitution pattern on the heteroaryl ring. Building on the initial work reported, a wider range of arylazoheteroarenes have also been studied, in order to fully investigate their properties and identify factors that control their thermal isomerisation rates. The azoheteroaryl photoswitches have been employed in two applications. The first, is the development of photoswitchable histone deacetylase (HDAC) inhibitors for use in photopharmacology, using either arylazopyrazoles or azobenzenes. Assays were carried out on human HDACs and bacterial homologues; sub-micromolar IC50 values were obtained for the bacterial HDACs and up to a 9-fold difference in activity between E- and Z-isomers was observed. Several tethered photoswitchable HDAC inhibitors were also developed – such compounds have potential use in industrial applications. The inhibitor-enzyme conjugates had reduced enzyme activity relative to the unbound enzyme, however no difference in activity was seen between the E- and Z-isomers. The second application was the development of an azobisimidazole photoswitchable base. This compound exhibited a difference in basicity between the E- and Z-isomers of 1.3 pKa units. The difference in basicity is due to the additional proton stabilisation in the protonated Z isomer, which is facilitated by the basic imidazole nitrogens, and can be used to reversibly control solution pH.
Supervisor: Fuchter, Matthew Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral