Tandem Systems for Two-Photon Uncaging of Bioactive Molecules

Photodeprotection of biological ligands with the combination of photolabile protecting groups (PPGs) and two-photon (2P) excitation techniques offers the possibility to control physiological phenomena with utmost spatial and temporal precision. Yet, designing PPGs with sufficient 2P photosensitivity still remains challenging. Direct enhancement of the 2P absorption properties usually relies on modifications of the PPG structure, which sometimes results in unpredictable and counterproductive effects on the uncaging quantum yield. In that respect, combining known PPGs with a suitable two-photon light-harvesting antenna within a modular architecture offers a promising alternative. In this Minireview, we highlight this versatile strategy, with a discussion of different tandem 2P uncagers, relying on photoinduced electron transfer (PET), triplet- energy transfer (TT-ET), or Forster resonance energy transfer (FRET) sensitization to enhance the 2P sensitivity of PPGs.