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Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems
Author(s) -
Long Yan,
Cao Bei,
Xiong Xiaolin,
Chan Albert S. C.,
Sun Raymond WaiYin,
Zou Taotao
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202013366
Subject(s) - bioorthogonal chemistry , transmetalation , chemistry , thioredoxin reductase , reactivity (psychology) , combinatorial chemistry , zebrafish , ligand (biochemistry) , in vivo , in vitro , catalysis , thioredoxin , biochemistry , enzyme , click chemistry , receptor , biology , medicine , alternative medicine , microbiology and biotechnology , pathology , gene
Controllably activating the bio‐reactivity of metal complexes in living systems is challenging but highly desirable because it can minimize off‐target bindings and improve spatiotemporal specificity. Herein, we report a new bioorthogonal activation approach by employing Pd(II)‐triggered transmetallation reactions to conditionally activate the bio‐reactivity of NHC–Au(I)–phenylacetylide complexes ( 1 a ) in vitro and in vivo. A combination of 1 H NMR, LC‐MS, DFT calculation and fluorescence screening assays reveals that 1 a displays a reasonable stability against biological thiols, but its phenylacetylide ligand can be efficiently transferred to Pd(II), leading to in situ formation of labile NHC–Au(I) species that is catalytically active inside living cells and zebrafish, and can meanwhile effectively suppress the activity of thioredoxin reductase, potently inhibit the proliferation of cancer cells and efficiently suppress angiogenesis in zebrafish models.