A Red-Shifted, Fast-Relaxing Azobenzene Photoswitch for Visible Light Control of an Ionotropic Glutamate Receptor

Journal of the American Chemical Society (Impact Factor: 11.44). 10/2013; 135(47). DOI: 10.1021/ja408104w
Source: PubMed

ABSTRACT Azobenzene photoswitches have become a dependable method for rapid and exact modulation of biological processes and material science systems. The requirement of ultraviolet (UV) light for azobenzene isomerization is not ideal for biological systems due to poor tissue penetration and potentially damaging effects. While modified azo-benzene cores with a red-shifted cis to trans isomerization have been previously described, they have not yet been incorporated into a powerful method to control protein function: the photoswitchable tethered ligand (PTL) approach. We report the synthesis and characterization of a red-shifted PTL, L-MAG0460, for the light-gated ionotropic glutamate receptor LiGluR. In cultured mammalian cells, the LiGluR+L-MAG0460 system is activated rapidly by illumination with 400-520 nm light to generate a large ionic current. The current rapidly turns off in the dark as the PTL relaxes thermally back to trans. The visible light excitation and single wavelength behavior considerably simplifies use and should improve utilization in tissue.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: New crownophanes containing 2,7-dioxyfluorenone and 4,4′-azobiphenoxy moieties linked by di-, tri-, tetra-, and pentaethylene glycol residues were synthesized. Just in case of obtaining largest crownophane with pentaethyleneglycol linkers, the dimeric cyclization product was also isolated in low yield. Obtained crownophanes, according to 1H NMR spectral data exist in conformations with closed intramolecular cavity in solution. Photoinduced E–Z isomerization of crownophane containing triethylene glycol linkers were investigated. The azobenzene fragment inclusion into crownophane reduces the photoisomerization rate compared to model 4,4′-dimethoxyazobenzene. In all the obtained crownophanes according to NMR, UV–Vis and X-ray data 4,4′-azobiphenoxy fragment is in E-configuration in solution as well as in the solid state. Crystal packing of all crownophanes has distinct feature—stacking arrangement of fluorenone moieties probably due to electrostatic dipole–dipole interactions. The formation of pseudorotaxane-type host–guest complexes of these crownophanes with paraquat dication was detected by FABMS and 1H NMR spectroscopy. UV–Vis spectra show no significant changes upon complex formation.
    Journal of inclusion phenomena and macrocyclic chemistry 04/2015; 81(3-4). DOI:10.1007/s10847-015-0484-0 · 1.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The photophysical behavior of the photochromic naphthopyran derivative 9 with photo-switching ability has been investigated in solution phase as well as in crystalline form. The proposed switching motifs might be a versatile framework in the development of photonic devices whose properties can be toggled between two states on exposure to electromagnetic radiations. The closed form of 9 undergoes reversible transformation upon irradiation with light by changing the molecular structure from ring closed conformation 9 to the ring opened form 10. The compound 9 exhibited first absorption signal at 238 nm with shoulder peak at 261 nm and second absorption signal at 353 nm while on photo-irradiation, the colorless solution of 9 turn to colored and there was ratiometric downfall in the signal intensity for shoulder signal at 261 nm as well as second absorption signal at 353 nm and ultimately results in the disappearance of these both signal after 20 min of irradiations. Meanwhile, the colorimetric change in the reaction solution and considerable shift in the absorption and emission signal intensity as well as position suggest the conformational changes in the molecules from less conjugate conformation 9 to the extended conjugated conformation 10.
    Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy 10/2014; 136. DOI:10.1016/j.saa.2014.10.016 · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A tetra-ortho-chloro substituted azobenzene unit was incorporated into a photoswitchable tethered ligand for ionotropic glutamate receptors. This compound confers the modified protein with the unusual optical responses of the substituted azo scaffold permitting channel opening with yellow and red light and channel closing with blue light.
    Chemical Communications 10/2014; 50(93). DOI:10.1039/C4CC06612J · 6.38 Impact Factor