Concurrent and orthogonal\xa0gold(I) and ruthenium(II) catalysis\xa0inside living cells

Cristian Vidal,María Tomás-Gamasa,Fernando López,José L Mascareñas,Paolo Destito

doi:10.1038/s41467-018-04314-5

Cristian Vidal, María Tomás-Gamasa + Show 3 more

Open Access

https://doi.org/10.1038/s41467-018-04314-5

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Journal: Nature Communications	Publication Date: May 15, 2018
Citations: 112	License type: open-access

Affiliation: University of Santiago de Compostela

Abstract

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.

Highlights

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
It is pertinent to note that while the term catalysis is commonly used, intracellular turnover has not been really investigated. These reactions have been essentially restricted to the use of copper, palladium, and ruthenium complexes[7,8,9,10,11,12,13,14,15,16], while other important transition metals in organometallic catalysis, such as gold[17,18,19], have not been yet explored
Isolated reports on the detection of toxic Au(III) salts in biological media, which rely on gold-promoted transformations, suggest the viability of using gold catalysis in biorelevant aqueous settings[20,21,22,23,24,25]

Summary

Introduction

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. We observed conversions higher than 70% with some of these gold complexes (see Supplementary Table 1), which confirm the viability of achieving the gold-catalyzed process in water, in absence of scavenging additives.

Results

Conclusion