Multiphoton Activation of Photo-Strain-Promoted Azide Alkyne Cycloaddition “Click” Reagents Enables in Situ Labeling with Submicrometer Resolution

Abstract

Irradiation of cyclopropenone-masked dibenzocyclooctynes with near-infrared pulses from a femtosecond laser triggers photodecarbonylation via nonresonant two- or three-photon excitation. Multiphoton-generated cyclooctynes undergo a SPAAC reaction with organic azides, yielding the expected triazoles. Multiphoton-triggered SPAAC (MP-SPAAC) enables high resolution 3-D photoclick derivatization of hydrogels and tissues.

Near‐IR Photochemistry for Biology: Exploiting the Optical Window of Tissue

“…By producing a cyclopropene which is decarboxylated via 2PA (or even potentially 3PA) NIR excitation to a strained cyclooctyne, they were able to reveal a partner for strained alkyne‐azide click chemistry (steps shown in Scheme 3). Click functionalization of a cyclopropene‐derivatized hydrogel was achieved with spatial precision down to less than a micrometer, implying a subcellular or potentially organelle‐specific level of control, only constrained by the optical diffraction limit . Selective attachment of azido dyes to irradiated sections of cyclopropene‐soaked rat intestines revealed the viability of the technique in the biological environment.…”

“…Adapted with permission from Ref. (48). which can then be reshaped postinstallation by photodegradation.…”

Photo‐induced and Rapid Labeling of Tetrazine‐Bearing Proteins via Cyclopropenone‐Caged Bicyclononynes

“…[37] Exploitation of photo-iEDDAC and genetically encodable tetrazine reporters to study receptor activation is focus of current studies in our lab.W ef urthermore expect that other fields such as the fabrication of microarrays, [38] biosensors,a nd the preparation of multifunctional material may benefit from this photo-triggered and rapid iEDDAC reaction. [37] Exploitation of photo-iEDDAC and genetically encodable tetrazine reporters to study receptor activation is focus of current studies in our lab.W ef urthermore expect that other fields such as the fabrication of microarrays, [38] biosensors,a nd the preparation of multifunctional material may benefit from this photo-triggered and rapid iEDDAC reaction.…”

“…Forschungsartikel aphoto-induced fashion, which might be especially attractive in combination with multi-photon activation of photo-DMBO compounds. [37] Exploitation of photo-iEDDAC and genetically encodable tetrazine reporters to study receptor activation is focus of current studies in our lab.W ef urthermore expect that other fields such as the fabrication of microarrays, [38] biosensors,a nd the preparation of multifunctional material may benefit from this photo-triggered and rapid iEDDAC reaction.…”

The Role of Photochemical Reactions in the Development of Advanced Soft Materials for Biomedical Applications

“…As the number of photons used to excite a molecule increases, the photons need to be more concentrated in the space for the absorption to occur, and as a consequence the resolution that can be achieved increases. This prospect has been explored using a cyclopropenone‐caged dibenzocyclooctynes (ODIBO) molecule, which only undergoes decarbonylation under 350 nm light producing SPAAC reactive alkynes . Functionalization experiments with this SPAAC reaction were performed using 2PE (690 nm) and three‐photon excitation (1050 nm).…”