Exporting Homogeneous Transition Metal Catalysts to Biological Habitats

Abstract

The possibility of performing designed transition-metal catalyzed reactions in biological and living contexts can open unprecedented opportunities to interrogate and interfere with biology. However, the task is far from obvious, in part because of the presumed incompatibly between organometallic chemistry and complex aqueous environments. Nonetheless, in the past decade there has been a steady progress in this research area, and several transition-metal (TM)-catalyzed bioorthogonal and biocompatible reactions have been developed. These reactions encompass a wide range of mechanistic profiles, which are very different from those used by natural metalloenzymes. Herein we present a summary of the latest progress in the field of TM-catalyzed bioorthogonal reactions, with a special focus on those triggered by activation of multiple carbon-carbon bonds.

Keywords: Biocatalysis; Bioorthogonal; Cell biology; Chemical biology; Organometallic catalysis.

Scheme 1

Hydrogenation of alkenes depicting common mechanistic steps in transition‐metal‐catalyzed reactions.

Scheme 2

Copper‐catalyzed alkyne azide cycloaddition (CuAAC).

Scheme 3

Pyridine directed CuAAC.

Scheme 4

Copper‐tristriazole complexes for CuAAC.

Scheme 5

Photoactivable ruthenium catalyst for thioalkyne‐azide coupling.

Scheme 6

Ruthenium‐catalyzed (2+2+2) cycloaddition in live cells.

Scheme 7

Bioorthogonal gold‐promoted cyclizations.

Scheme 8

HSA‐gold metalloenzyme for the generation of 5‐methylphenantrenium cores.

Scheme 9

Palladium‐catalyzed depropargylations in cells and in vivo. (Dppf)=diphenylphosphinoferrocoene.

Scheme 10

Palladopeptide catalyzed uncaging of alkyne‐containing molecules.

Scheme 11

Cleavage of substituted alkynes. (Cod)=cyclooctadiene.

Scheme 12

Gold‐catalyzed labelling of organs. Reproduced from ref. 25 with permission from Wiley‐VCH GmbH, © 2017.

Scheme 13

Sonogashira couplings in live cells.

Scheme 14

Ruthenium‐catalyzed deallyloxylation.

Scheme 15

Cell tagging through Ru‐catalyzed deallylation.

Scheme 16

Deallylation as a mean for bacterial cell survival.

Scheme 17

Applications of ruthenium catalysts with designed ligands for target‐selective deallylations.

Scheme 18

Ruthenium metalloenzymes for metathesis.

Scheme 19

Palladium‐catalyzed Heck reaction inside live cells.

Scheme 20

Ruthenium‐catalyzed isomerization in living cells.

Scheme 21

Palladium‐catalyzed decaging of a tyrosine exposing the OH motif to kinase activity.

Scheme 22

Bioorthogonal iron‐catalyzed azide reduction.

Scheme 23

Suzuki‐Miyaura coupling in the surface of E. Coli.

Scheme 24

Iridium‐catalyzed reduction of aldehydes.

Scheme 25

Copper‐catalyzed carbene insertions.

Scheme 26

Iridium‐photocatalyzed proximity labeling using diazirines.

Scheme 27

Nucleic acid‐templated photocatalytic uncaging of a Rhodamine.