Azobenzenes can achieve near-infrared photocontrol in biological systems, with quantitative Z→E photoisomerization, via singlet manifold photoredox

Here we develop a high-performance approach to photoswitching, by exploiting singlet manifold photoredox between azobenzenes and covalently attached auxiliary chromophores. This enables well-penetrating red/NIR light of 630-740 nm, to which azobenzenes usually do not respond, to perform Z→E photoisomerisation that is also 100% complete and highly photon-efficient. Crucially, this process is biocompatible, tolerates molecular oxygen, is photostable, and it avoids the drawbacks of triplet photochemistry; and substituent patterns of azobenzenes do not need re-engineering to harness it. We provide a library of redox potentials to predict photoredox performance, show its tolerance to linker length, and show that E→Z-promoting tetra-ortho-substitutions can be combined with photoredox to give fast and efficient bidirectional Z⇄E photoswitches for the visible/NIR. We then demonstrate the first use of single photon NIR light for reversible photopharmaceutical control in live cells under physiological conditions, by modulating G protein-coupled receptor activity. These stringent assays show singlet photoredox switching is a robust method for NIR photocontrol that should find high-performance applications in materials, in biophysics, and for "chemical optogenetics v2.0" in living systems.