RT Journal Article
T1 Exporting Metal-Carbene Chemistry to Live Mammalian Cells: Copper-Catalyzed Intracellular Synthesis of Quinoxalines Enabled by N-H Carbene Insertions
A1 Gutiérrez Hernández, Sara
A1 Tomás Gamasa, María
A1 Mascareñas Cid, José Luis
K1 Copper
K1 Bioorthogonal chemistry
K1 Intracellular chemistry
K1 Metal carbenes
K1 Metal catalysis
AB Implementing catalytic organometallic transformations in living settings can offer unprecedented opportunities in chemical biology and medicine. Unfortunately, the number of biocompatible reactions so far discovered is very limited, and essentially restricted to uncaging processes. Here, we demonstrate the viability of performing metal carbene transfer reactions in live mammalian cells. In particular, we show that copper (II) catalysts can promote the intracellular annulation of alpha-keto diazocarbenes with ortho-amino arylamines, in a process that is initiated by an N-H carbene insertion. The potential of this transformation is underscored by the in cellulo synthesis of a product that alters mitochondrial functions, and by demonstrating cell selective biological responses using targeted copper catalysts. Considering the wide reactivity spectrum of metal carbenes, this work opens the door to significantly expanding the repertoire of life-compatible abiotic reactions
PB Wiley
SN 1433-7851
YR 2021
FD 2021
LK http://hdl.handle.net/10347/26954
UL http://hdl.handle.net/10347/26954
LA eng
NO Angew. Chem. Int. Ed. 2021, 60, 22017–22025
NO This work has received financial support from Spanish grants (PID2019-108624RB-I00, RTI2018-093813-J-I00 and ORFEO-CINQA network CTQ2016-81797-REDC), the Consellería de Cultura, Educación e Ordenación Universitaria (2015-CP082, ED431C-2017/19 and Centro Singular de Investigación de Galicia accreditation 2019–2022, ED431G 2019/03), the European Union (European Regional Development Fund-ERDF corresponding to the multiannual financial framework 2014–2020), and the European Research Council (Advanced Grant No. 340055). S.G. thanks the European Union (European Regional Development Fund, Interreg V-A POCTEP España-Portugal programme, 2iqbioneuro project) and M.T.G. thanks the financial support from the Agencia Estatal de Investigación (RTI2018-093813-J-I00)
DS Minerva
RD 23 abr 2026