Photoswitchable and long-lived seven-membered cyclic singlet diradicals for the bioorthogonal photoclick reaction

Annularly 1,3-localized singlet diradicals are energetic and homolytic intermediates, but commonly too short-lived for widespread utilization. Herein, we describe a direct observation of a long-lived and seven-membered singlet diradical, oxepine-3,6-dione-2,7-diyl (OXPID), via spectroscopic experiments and also theoretical evidence from computational studies, which is generated via photo-induced ring-expansion of 2,3-diaryl-1,4-naphthoquinone epoxide (DNQO). The photo-generated OXPID reverts to the thermally stable σ-bonded DNQO with t(1/2) in the μs level, thus constituting a novel class of T-type molecular photoswitches with high light-energy conversion efficiency (η = 7.8–33%). Meanwhile, the OXPID is equilibrated to a seven-membered cyclic 1,3-dipole as an electronic tautomer that can be captured by ring-strained dipolarophiles with an ultrafast cycloaddition rate (k(2CA) up to 10(9) M(−1) s(−1)). The T-type photoswitchable DNQO is then exploited to be a highly selective and recyclable photoclick reagent, enabling spatiotemporal-resolved bioorthogonal ligation on living cell membranes via a tailored DNQO-Cy3 probe.