Concurrent and orthogonal gold(I) and ruthenium(II) catalysis inside living cells

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a gold-mediated C-C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner.This work has received financial support from Spanish grants (SAF2013-41943-R, SAF2016-76689-R, Orfeo-cinqa network CTQ2016-81797-REDC), the Xunta de Galicia (2015-CP082, ED431C 2017/19, and Centro Singular de Investigación de Galicia accreditation 2016-2019, ED431G/09), the European Union (European Regional Development Fund-ERDF), and the European Research Council (Advanced Grant No. 340055). M.T.G. thanks the Ministerio de Economía y Competitividad for the Juan de la Cierva-Incorporación fellowship (IJCI-2015-23210). The authors thank R. Menaya- Vargas for excellent technical assistance and M. Marcos for helpful contributions on MS analysis.Peer Reviewe