C.K. acknowledges the HPC resources of CINES and IDRIS under the allocations 2016- [x2016080649] made by GENCI.International audienceNear-infrared two-photon (TP)-induced photorelease (uncaging) of bioactive molecules such as drugs has attracted considerable attention because of its ability to elucidate mechanistic aspects of biological processes. This short review summarizes recent developments in the design and synthesis of TP-responsive chromophores

A new chromophore, 2-(4-nitrophenyl)benzofuran (NPBF), was designed for two-photon (TP) uncaging using near-IR light. The TP absorption (TPA) cross-sections of the newly designed NPBF chromophore were determined to be 18 GM at 720 nm and 54 GM at 740 nm in DMSO. The TP uncaging reaction of a caged benzoate with the NPBF chromophore quantitatively produced benzoic acid with an efficiency (δu) of ∼5.0 GM at 740 nm. The TP fragmentation of an EGTA unit was observed with δu = 16 GM. This behavior makes the new chromophore a promising TP photoremovable protecting group for physiological studies.

International audienceAmong biologically active compounds, calcium ions (Ca2+) are one of the most important species in cell physiological functions. Development of new calcium chelators with two-photon absorption (TPA) properties is a state-of-the-art challenge for chemists. In this study, we report the first and efficient synthesis of 5-bromo-2-nitrobenzyl-substituted ethylene glycol tetraacetic acid (EGTA) as a platform for a new generation of calcium chelators with TPA properties in the near-infrared region. New calcium chelators with high TPA properties, that is, a two-photon (TP) fragmentation efficiency of δu = 20.7 GM at 740 nm for 2-(4-nitrophenyl)benzofuran (NPBF)-substituted EGTA (NPBF-EGTA, Kd = 272 nM) and δu = 7.8 GM at 800 nm for 4-amino-4′-nitro-1,1′-biphenyl (BP)-substituted EGTA (BP-EGTA, Kd = 440 nM) derivatives, were synthesized using Suzuki–Miyaura coupling reactions of the bromide with benzofuran-2-boronic acid and 4-(dimethylamino)phenyl boronic acid, respectively. The corresponding acetoxymethyl (AM) esters were prepared and successfully applied to the Ca2+-uncaging reaction triggered by TP photolysis in vivo