Michelini Lorenzo, Slaney Tanya, Virk Seerat, Rafic Estefanía, Qie L Charlie, Corejova Klara, Lepage Mathieu L, Musolino Stefania F, Oliver Allen G, Etchenique Roberto, Hong W David, DiLabio Gino A, Wulff Jeremy E
Department of Chemistry, University of Victoria Victoria BC V8W 3V6 Canada
Department of Chemistry, Sapienza University of Rome P.le A. Moro 5 00185 Rome Italy.
Chem Sci. 2024 Dec 2;16(2):970-979. doi: 10.1039/d4sc06427e. eCollection 2025 Jan 2.
Diazirines are versatile carbene precursors that are extensively used in biological target identification experiments. However, their photo-activation wavelength ( 365 nm) precludes their use in living organisms. Here we show that a reconceptualization of the diazirine hybridization state leads to conjugation of the diazirine motif to longer-wavelength chromophores. In a model diazirine-fluorene conjugate, we are able to achieve direct activation (and subsequent C-H insertion) with >450 nm light for the first time. Two-photon activation using near-IR light is also achieved, suggesting the possibility to prepare new diazirine probes for conducting target identification experiments in deep tissue.
重氮丙环是用途广泛的卡宾前体，在生物靶点识别实验中被广泛应用。然而，它们的光激活波长（365纳米）使其无法用于活体生物。在此我们表明，对重氮丙环杂化态的重新概念化导致重氮丙环基序与长波长发色团共轭。在一个重氮丙环-芴共轭物模型中，我们首次能够用波长大于450纳米的光实现直接激活（以及随后的C-H插入）。还实现了使用近红外光的双光子激活，这表明有可能制备新的重氮丙环探针，用于在深部组织中进行靶点识别实验。
