A bisazobenzene crosslinker that isomerizes with visible light

Abstract

Summary Background: Large conformational and functional changes of azobenzene-modified biomolecules require longer azobenzene derivatives that undergo large end-to-end distance changes upon photoisomerization. In addition, isomerization that occurs with visible rather than UV irradiation is preferred for biological applications. Results: We report the synthesis and characterization of a new crosslinker in which a central piperazine unit links two azobenzene chromophores. Molecular modeling indicates that this crosslinker can undergo a large change in end-to-end distance upon trans,trans to cis,cis isomerization. Photochemical characterization indicates that it does isomerize with visible light (violet to blue wavelengths). However, the thermal relaxation rate of this crosslinker is rather high (τ½ ~ 1 s in aqueous buffer at neutral pH) so that it is difficult to produce large fractions of the cis,cis-species without very bright light sources. Conclusion: While cis-lifetimes may be longer when the crosslinker is attached to a biomolecule, it appears the para-piperazine unit may be best suited for applications where rapid thermal relaxation is required.

Positional isomers of bispyridine benzene derivatives induce efficacy changes on mGlu5 negative allosteric modulation

“…We were able to detect a nearly complete photoisomerisation of compound 19b, since the profile of the UV-Vis spectrum obtained after violet illumination was the same as that obtained for the cis isomer peak detected by HPLC-PDA-MS (supplementary material). However, for compounds 19a and 21a-b we did not detect satisfactory photoisomerisation after illumination with violet light, in a similar manner to other previously reported bisazocompounds [34] (supplementary material). This indicates that not all azo-compounds display a suitable photoisomerisation response for obtaining a high population of cis isomers under illumination, which is a necessary condition for efficient on/off receptor switching.…”

Azobenzene switch with a long-lived cis-state to photocontrol the enzyme activity of a histone deacetylase-like amidohydrolase

“…Many artificially generated light sensitized proteins as well as naturally occurring species, peptides or several azobenzene crosslinkers exhibit partly very fast cis-totrans relaxation rates from seconds to hours (Genick et al, 1998;Shimoboji et al, 2002;Banghart et al, 2004;Lanyi, 2004;Borisenko and Woolley, 2005;Gorostiza et al, 2007;Volgraf et al, 2007;Sadovski et al, 2009;Schierling et al, 2010;Samanta et al, 2012), which limits these systems for potential long-term applications and systematic photoswitching processes. Therefore, great emphasis was placed on thorough and accurate measurements of decelerated cis-to-trans relaxation kinetics of the azobenzene switch attached to the protein surface.…”

Two-photon absorption and two-photon-induced isomerization of azobenzene compounds

“…108 It is worth to notice that bistable photoswitches provide an excellent starting point for designing two-photon active photoswitches as it is less difficult, by prolonged irradiation, to produce large steady state fraction of the cis isomer. 42,110,111…”