PUBLICATION
Bioorthogonal Activation of Dual Catalytic and Anti-Cancer Activities of Organogold(I) Complexes in Living Systems
- Authors
- Long, Y., Cao, B., Xiong, X., Chan, A.S.C., Sun, R.W., Zou, T.
- ID
- ZDB-PUB-201120-36
- Date
- 2020
- Source
- Angewandte Chemie (International ed. in English) 60(8): 4133-4141 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Alkynes/chemistry
- Animals
- Antineoplastic Agents/chemical synthesis
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/metabolism
- Antineoplastic Agents/pharmacology
- Catalysis
- Cell Line, Tumor
- Cell Survival/drug effects
- Coordination Complexes/chemistry*
- Coordination Complexes/metabolism
- Coordination Complexes/pharmacology
- Density Functional Theory
- Embryo, Nonmammalian/chemistry
- Embryo, Nonmammalian/metabolism
- Gold/chemistry*
- Humans
- Methane/analogs & derivatives
- Methane/chemistry
- Optical Imaging
- Palladium/chemistry
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 33151608 Full text @ Angew. Chem. Int. Ed. Engl.
Citation
Long, Y., Cao, B., Xiong, X., Chan, A.S.C., Sun, R.W., Zou, T. (2020) Bioorthogonal Activation of Dual Catalytic and Anti-Cancer Activities of Organogold(I) Complexes in Living Systems. Angewandte Chemie (International ed. in English). 60(8):4133-4141.
Abstract
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 (e.g., 1a ) in vitro and in vivo. A combination of 1 H NMR, LC-MS, DFT calculation and fluorescence screening assays reveals that 1a 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. Of note, by introducing RGD-functionalized Pd(II) inducers, 1a is endowed with highly selective cytotoxicity towards cancer cells with minimal influence on the normal counterparts.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping