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. 2020 Mar 10;11(13):3390–3396. doi: 10.1039/c9sc06540g

Precursors and photo-released bioorthogonal functionalities to develop photo-controllable bioorthogonal reactions.

Bioorthogonal functionality obtained after photolysis Photo-labile precursor Typical conditions for photolysis Advantages/limits for biological applications
graphic file with name c9sc06540g-u1.jpg graphic file with name c9sc06540g-u2.jpg 1–3 min' irradiation in a mini-Rayonet photoreactor equipped with multiple 350 nm fluorescent tubes26,27 Photo-SPAAC enabled photo-control on labeling azido-bearing biomolecules in live cells, with concern on diffusion of the in situ formed strained alkyne due to fast kinetics in photolysis but a relatively slow rate of SPAAC
graphic file with name c9sc06540g-u3.jpg graphic file with name c9sc06540g-u4.jpg
graphic file with name c9sc06540g-u5.jpg graphic file with name c9sc06540g-u6.jpg 5 min' irradiation at 365 nm from a UV lamp VL-215.L (ref. 28) Photo-IEDDAC reactions with fast kinetics enabled rapid labeling of tetrazine-bearing proteins within minutes at low μM concentrations. Future applications on mammalian cells need more biocompatible light than UV
graphic file with name c9sc06540g-u7.jpg graphic file with name c9sc06540g-u8.jpg Pulsed laser at 375 nm (ref. 29) Ultra-fast and efficient photo-release of dibenzosilacyclohept-4-yne achieved well-balanced combination of reactivity and stability in aqueous solutions. Photo-stability of the released alkyne exposed to a laser at the irradiation wavelength was a concern
graphic file with name c9sc06540g-u9.jpg graphic file with name c9sc06540g-u10.jpg Femtosecond laser for two-photon (690 nm) or thee-photon (1050 nm) excitation30 Multiphoton activation of strained alkynes allowed MP-SPAAC with low phototoxicity and deep penetration in biological systems, with a limit in the region of interest irradiated with a two-photon or three-photon laser
graphic file with name c9sc06540g-u11.jpg graphic file with name c9sc06540g-u12.jpg 30–180 min' UV light irradiation with a 350 W medium pressure Hg arc lamp32 Simple uncaging approach helped to realize photo-control on the highly specific Staudinger–Bertozzi ligation, with concern on the biocompatibility of the light irradiation conditions with live cells
graphic file with name c9sc06540g-u13.jpg graphic file with name c9sc06540g-u14.jpg 20–40 min' irradiation with broadband visible light (>420 nm) from a 500 W Hg lamp33 Photo-uncaging quantum efficiency of Staudinger ligation triggered by visible light is lower than UV uncaging
graphic file with name c9sc06540g-u15.jpg graphic file with name c9sc06540g-u16.jpg Hours of irradiation under UV34 Module photo-cage of cyclopropane needs to be further optimized for real biological applications