Gold-Triggered Uncaging Chemistry in Living Systems.

Ana M Pérez‐López,Silvia Irusta,Paul M Brennan,Belén Rubio‐Ruiz,Jesús Santamaría,Catherine Adam,Thomas L Bray,Víctor Sebastián,Lloyd Hamilton,Guy C Lloyd‐Jones,Asier Unciti‐Broceta,Dirk Sieger

doi:10.1002/anie.201705609

Abstract

Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate the fate of molecules in complex biological systems. A bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous gold catalysis and facilitates the activation of a structurally diverse range of therapeutics in cancer cell culture. Furthermore, this solid‐supported catalytic system enabled locally controlled release of a fluorescent dye into the brain of a zebrafish for the first time, offering a novel way to modulate the activity of bioorthogonal reagents in the most fragile and complex organs.

Highlights

The emerging field of bioorthogonal catalysis[2] has produced a wealth of creativity in a variety of applications, ranging from biomolecule labeling,[3a–c] metabolite detection[3d] and intra/subcellular probe release,[3e–h] to in situ enzyme[3i,j] and prodrug activation.[3k–o] Substoichiometric activity and access to a greater diversity of chemical processes and functionalities are some of the added benefits provided by abiotic transition metals to the current bioorthogonal toolbox, expanding the boundaries of this central field of research.[4]
Scheme 1. a) AuIII-mediated bioorthogonal amidation reported by Tanaka and coworkers.[5] b) The solid-supported gold-catalyzed uncaging strategy developed in this work
Solid-supported gold nanoparticles (Au-NP) have attracted the interest of chemists searching for greener catalysts, because such catalysts are recyclable, gold is safe to handle, and it demonstrates a remarkable ability to catalytically mediate oxidative reactions at or even below ambient temperatures.[7]

Summary

Edinburgh Research Explorer

Citation for published version: Perez-Lopez, AM, Rubio Ruiz, B, Sebastian, V, Hamilton, L, Adam, C, Bray, TL, Irusta, S, Brennan, PM, Lloyd-Jones, GC, Sieger, D, Santamaria, J & Unciti-Broceta, A 2017, 'Gold-Triggered Uncaging Chemistry in Living Systems', Angewandte Chemie, vol 129, no.

Bioorthogonal Catalysis

Conflict of interest