Near-Infrared Photoswitching of Azobenzenes under Physiological Conditions

Biological tissue exhibits an absorbance
minimum in the near-infrared
between 700 and 900 nm that permits deep penetration of light. Molecules
that undergo photoisomerization in this bio-optical window are highly
desirable as core structures for the development of photopharmaceuticals
and as components of chemical-biological tools. We report the systematic
design, synthesis, and testing of an azobenzene derivative tailored
to undergo single-photon photoswitching with near-infrared light under
physiological conditions. A fused dioxane ring and a methoxy substituent
were used to place oxygen atoms in all four ortho positions, as well as two meta positions, relative
to the azobenzene NN double bond. This substitution pattern,
together with a para pyrrolidine group, raises the
pKa of the molecule so that it is protonated
at physiological pH and absorbs at wavelengths >700 nm. This azobenzene
derivative, termed DOM-azo, is stable for months in neutral aqueous
solutions, undergoes trans-to-cis photoswitching with 720 nm light, and thermally reverts to the stable trans isomer with a half-life near 1 s.