State-of-the art photoactivation strategies in chemical biology provide spatiotemporal control and visualization of biological processes. However, using high energy light (l < 500 nm) for substrate or photocatalyst sensitization can lead to background activation of photoactive small molecule probes and reduce its efficacy in complex biological environments. Here we describe the development of targeted aryl azide activation via deep red light (l = 660 nm) photoredox catalysis and its use in photocatalyzed proximity labeling. We demonstrate that aryl azides are converted to triplet nitrenes via a novel redox-centric mechanism and show that its spatially localized-formation requires both red light and a photocatalyst-targeting modality. This technology was applied in different colon cancer cell systems for targeted protein environment labeling of epithelial cell adhesion molecule (EpCAM). We identified a small subset of proteins with previously known and unknown association to EpCAM, including CDH3, a clinically relevant protein that shares high tumor selective expression with EpCAM.

A system has been developed to activate a latent ruthenium olefin metathesis catalyst using deep red to near-infrared light (600–800 nm) in conjunction with an osmium(II) photocatalyst that is directly excited to its triplet state via spin-forbidden excitation. An excited-state single-electron reduction of a latent solvent-coordinated, cationic precatalyst is proposed as the operating mechanism for activation and photocontrol, as probed via in situ LED NMR kinetic studies and cyclic voltammetry. Excellent levels of spatiotemporal control are found under light irradiation. NIR olefin metathesis exhibits improved light penetration through barriers over shorter wavelengths of light, a control element that was deployed to mold dicyclopentadiene via ring-opening metathesis polymerization.

The development of a system to electrochemically control ruthenium-catalyzed olefin metathesis is reported. Catalyzed by a commercially-available bis-NHC Ru complex, this system displays a broad substrate scope with very short reaction times, as well as excellent levels of temporal control over metathesis with only electricity as a stimulus.