Photoswitches are a subtype of molecular switch that undergo a reversible structural change upon irradiation with light to adopt a different configuration. Activation of a molecular switch by light offers several advantages. In addition to being traceless, light can be precisely controlled in its intensity (dosage control) and can be focused with sub-micron accuracy with a high temporal and spatial resolution. Consequently, photoswitches ideally lend themselves to the construction of light-responsive pharmaceutical compounds, a field that is described by the term photopharmacology.

The most common motif that is used in this approach is the azobenzene moiety, owing to the large geometrical change that results from adopting a different configuration. Azobenzene-based photoresponsive systems have also been successfully applied in several biological systems. The azobenzene moiety is synthetically accessible via various pathways (Mills reaction, oxidative/reductive coupling, azo coupling), and its photochromic properties can easily be finetuned.  The thermodynamically more stable trans isomer adopts an extended planar configuration with a dipole moment close to zero, while the higher energy, metastable cis isomer is more polar and exhibits unfavorable steric interactions.

Interconversion between the trans and cis isomer of the azobenzene motif in a photoswitchable peptide.

An additional benefit of the azobenzene motif is its high degree of reversibility. It can undergo approximately 100 switching cycles without detectable photodegradation or loss of responsiveness. However, although the trans isomer can be regenerated 100% by thermal relaxation, full conversion of one or the other isomer by irradiation with visible light is impossible owing to a substantial overlap of the absorption spectra of both isomers.

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