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Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled -for the first time- modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

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., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Being recognized as the best‐tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly‐catalytic Au‐polymer composite by assembling ultrasmall Au‐nanoparticles at the protein‐repelling outer layer of a co‐polymer scaffold via electrostatic loading. Illustrating the in vivo‐compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled ‐for the first time‐ modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Thiole sind allgegenwärtig in lebenden Systemen, und ihre starke Bindung an Goldoberflächen hält andere funktionelle Gruppen fast vollständig von diesen fern. In ihrer Zuschrift auf S. 12727 berichten J. Santamaría, A. Unciti ‐ Broceta et al. über Gold ‐ Heterogenkatalysatoren für die bioorthogonale Aktivierung zugelassener Tumortherapeutika (durch O/N ‐ Depropargylierung) in Krebszellkulturen und die erste Aktivierung einer bioorthogonalen Sonde im Gehirn von Zebrafischen. [ABSTRACT FROM AUTHOR]

Thiols are ubiquitous in living systems where they bind strongly to gold surfaces and render interactions with other functional groups basically non‐existent. In their Communication on page 12548 ff., J. Santamaría and A. Unciti‐Broceta et al. describe heterogeneous gold catalysts that enable bioorthogonal uncaging (by O/N‐depropargylation) of clinically approved anticancer drugs in cancer cell culture, and the first intracranial activation of a bioorthogonal probe in a zebrafish. [ABSTRACT FROM AUTHOR]

[Display omitted] The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O -propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture. [ABSTRACT FROM AUTHOR]