Bidirectional Photoswitching of a Tailored Azobenzene with Red and Far-Red Light Involving Triplet Sensitization in...

Shifting action spectrum of azobenzene-based photopharmaceuticals toward bio-optical window is highly desired, since red/far-red light offers improved tissue penetration and reduced cellular toxicity. While unidirectional photoswitching (trans-to-cis and cis-to-trans) of azobenzenes (AZO) with red/far-red light is known in separate systems, achieving bidirectional photoswitching in a single system faces issues of spectral overlaps. Here, bidirectional photoswitching of a tailored azobenzene is achieved in a single bio-relevant solution with red and far-red light excitation. A new azobenzene molecule (AZO-N) bearing four ortho-methoxy, and one para-N donor lipophile is synthesized. The AZO-N exhibits separate n-π* absorption bands and triplet energies for trans and cis isomers. As a result, trans-to-cis photoswitching is observed upon 625 nm excitation at the tail of the red-shifted n-π*absorption band via direct absorption, whereas cis-to-trans photoswitching is enabled upon 730 nm excitation through triplet sensitization. Further, triplet sensitization of AZO-based molecules could lead to singlet oxygen generation-experiments in the presence of serum albumin and glutathione (biological oxidative stress addressors), suggest no effect of singlet oxygen on the triplet-sensitization of cis-AZO-N, and non-significant change in the fingerprint all-α secondary structure of serum albumin. This advance presents modular design principles to develop practically functional azo-based photopharmaceuticals.