Photoswitchable Cytotoxins

Exhaustive Catalytic ortho-Alkoxylation of Azobenzenes: Flexible Access to Functionally Diverse Yellow-Light-Responsive Photoswitches

“…Like most photoswitches (typically, flat aromatics), azobenzenes have very poor water solubility and tend to aggregate. This complicates their photoswitching and spectra , and hampers applications from materials sciences to biology . Exhaustive alkoxylation with diols could be a late-stage solubilizing method that also provides beneficial tetra- ortho photoresponse, without crowding the para positions needed for “azo-extension” and “azo-linker” photopharmacology and without charges that complicate bioactivity.…”

Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity

“…Misinterpreting photosensitisation as lit-isomer toxicity is a permanent risk when working with photopharmaceuticals. 26 It would be a puzzling cellular mechanism of action to propose for StyBtz2 , since it is unclear why other structurally related StyBtz would not show similar activity; however, to exclude it, we tested StyBtz2 for photosensitization using the photobleaching reporter 1,3-diphenylisobenzofuran (DPBF). Its photobleaching rate was insignificantly affected by StyBtz2 (10 μM), in comparison to reference photosensitizer methylene blue (MB, 5 μM) which accelerated photobleaching by >10% (Fig.…”

“…Relaxation is the most important of these: combining E → Z photoswitching with biologically fast Z → E relaxation would allow StyBtz/StyTz to be patterned into specified E / Z -isomer distributions, with the biologically appropriate spatiotemporal resolution needed for MT studies. 26 Neither StyBtz nor StyTz have been tested as E ⇄ Z -photoisomerisable photopharmaceuticals, not even in cell-free assays. However, (1) StyBtz photochemistry has been studied: they E ⇄ Z -photoisomerise reversibly in organic and aqueous media, 27 and have fluorescence emission around 500 nm 28 (note the similarity of push–pull StyBtz to truncated Cy dyes); and (2) some E -StyBtz, though structurally distant, have been reported to have general antiproliferative activity against eukaryotic cells 29–32 (and further reports of E -StyBtz for cell-free or bacterial applications have also been made 33 ).…”

Visible Light Control over the Cytolytic Activity of a Toxic Pore-Forming Protein

“…In this context, light is an excellent stimulus that can be easily externally delivered at specific time points and locations. − Organic chemistry provides artificial actuators that can reversibly respond to different wavelengths of light: molecular photoswitches. − Photoswitches are small organic molecules that change their shape and properties in a reversible manner upon irradiation with light . They have been applied, inter alia , in photopharmacological approaches to control the action of small molecules, DNA, peptides, and, most importantly in this context, proteins. ,,− The structure and activity of numerous proteins have been manipulated by light with the help of covalently attached photoswitches via single attachment or two-point attached cross-linkers. ,, …”

“… 40 They have been applied, inter alia , in photopharmacological approaches to control the action of small molecules, DNA, peptides, and, most importantly in this context, proteins. 36 , 38 , 41 − 47 The structure and activity of numerous proteins have been manipulated by light with the help of covalently attached photoswitches via single attachment or two-point attached cross-linkers. 42 , 44 , 48 …”