J. Chem. Am. Soc., published online 10 June 2013; doi:10.1021/ja402220t

Credit: A. WOOLLEY

Photochemical tools allow scientists to use light to control the on and off state of a molecule. For in vivo application of these tools, switchable compounds must be responsive to red light; this requirement has limited applications of the popular azobenzene scaffold, for which no red light–activated derivatives are known. Samanta et al. now report a series of red light–activated azobenzenes and demonstrate their photoswitching properties in vivo. The authors showed that tetra-ortho-methoxy–substituted azobenzene can drive helix-to-coil transitions in FK-11, a peptide known to switch between conformations in response to isomerization of azobenzenes, and in other peptides in response to red light in vitro. In cells, azobenzene derivatives are also subject to reduction by glutathione, and the tetra-ortho-methoxy azobenzenes suffered from this weakness. The authors identified a tetra-ortho-chloro azobenzene that underwent stable cis-trans isomerization in response to red light and was resistant to reduction by glutathione. When linked to a fluorescent reporter peptide, this azobenzene yielded red light–mediated photocontrol in zebrafish embryos. Although it remains to be shown that these tools can be applied to interrogate a biological system in vivo, the development of red light–dependent, glutathione-resistant photochemical tools that can be readily derivatized makes these experiments possible.