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

• Published in: Chemical science (Cambridge) 2023-11, Vol.14 (45), p.13254-13264
• Main Authors: Hu, Fuqiang, Zhang, Cefei, Liu, Zhihao, Xie, Xinyu, Zhao, Xiaohu, Luo, Yanju, Fu, Jielin, Li, Baolin, Hu, Changwei, Su, Zhishan, Yu, Zhipeng
• Format: Article
• Language: English
• Subjects: Cell membranes; Cycloaddition; Dipoles; Energy conversion efficiency; Reagents; Thermal stability
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc03675h

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. Microsecond photoswitch cycles between DNQO and a singlet diradical (SDR) were clarified with energy conversion η