Reductive stability evaluation of 6-azopurine photoswitches for the regulation of CKIα activity and circadian rhythms

Abstract

Photopharmacology develops bioactive compounds whose pharmacological potency can be regulated by light. The concept relies on the introduction of molecular photoswitches, such as azobenzenes, into the structure of known enzyme...

Molecular photoswitches in aqueous environments

“…206,207 In the context of watersoluble photoswitches, this aspect is of greatest importance in biological systems, as the reducing agent glutathione is present in the cell. 6,30 Similar observation have also been made for some heteroaromatic analogues, like purines 177 and thiazoles, 180 while arylazopyrazoles appear to be less sensitive to these conditions. 157,185 Moreover, the nature of the solvent has an influence on the thermal stability of the metastable form, as it stabilizes or destabilizes the transition state geometry of the reisomerization reaction.…”

“… 206,207 In the context of water-soluble photoswitches, this aspect is of greatest importance in biological systems, as the reducing agent glutathione is present in the cell. 6,30 Similar observation have also been made for some heteroaromatic analogues, like purines 177 and thiazoles, 180 while arylazopyrazoles appear to be less sensitive to these conditions. 157,185 …”

“…157,158 As in classical azobenzenes, the E form is planar and the Z is twisted, adopting either a helical conformation in the case of 6-membered rings, and a T-shaped one if a 5-membered heteroaryl ring is directly attached to the diazo bond. 157,158,165 Moreover, the photophysical properties are influenced by the presence of the hetero atoms, rendering azoswitches based on pyridine, [166][167][168][169][170] indole, [171][172][173][174] indazole, 175 purine, 176,177 pyrimidine, 178,179 pyrrole, 165 imidazole, 165,[180][181][182] pyrazole, 46,165,[183][184][185][186][187][188] oxazole, 189 thiazole, 180 thiophene, [190][191][192] etc., generally responsive to light of longer wavelength. In contrast, in classical azobenzenes the UV-Vis absorption spectrum can be tuned by introducing, for instance, (push-pull) substituents in the para position 156,193,194 or tetraortho substituents [195][196]...…”

Electrochemical Potential‐Driven High‐Throughput Molecular Electronic and Spintronic Devices: From Molecules to Applications

“…[135][136][137] Several researchers have been aiming at developing nanometric molecular junctions to examine photostimulated charge transport phenomena. [138][139][140][141][142][143] Fore xample,L acroix and co-workers fabricated molecular junctions to study ultraviolet followed by visible-light-driven charge transport. [144] Theb ottom electrode was prepared by electrografting the photosensitive diazonium salt of perfluoro-1,2-bis(2-(4-aminophenyl)-5methylthien-4-yl)-cyclopentene (DAE-(C 6 H 4 NH 2 ) 2 )o nb oth gold and glassy carbon contacts.B yv arying the electrochemical reduction parameters,layers of two different thicknesses,3 .1 nm and 8.6 nm, were achieved.…”

Design and development of a photoswitchable DFG-out kinase inhibitor

“…1A). [5][6][7][8][9][10] The development of these compounds has been challenging because of common photopharmacology issues, [10][11][12] such as insufficient isomeric enrichment in the photo-stationary distributions (PSDs); narrow bioactive discrepancy between the two isomers; rapid thermal isomerization; and reduction by, e.g., dithiothreitol (DTT) and glutathione (GSH), which are typically used for protein stabilisation in biological assays.…”