A diazirine's central carbon is sp2-hybridized, facilitating conjugation to dye molecules

Abstract

Diazirines are versatile carbene precursors that are extensively used in biological target identification experiments. However, their photo-activation wavelength (ca. 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.