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Published on: May 28, 2014
Alkylgold(III) Complexes Undergo Unprecedented Photo-Induced β-Hydride Elimination and Reduction for Targeted Cancer
Jia Jiang1, Bei Cao2, Yuting Chen1
1Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, P. R. China.
Abstract:
Spatiotemporally controllable activation of prodrugs within tumors is highly desirable for cancer therapy to minimize toxic side effects. Herein we report that stable alkylgold(III) complexes can undergo unprecedented photo-induced β-hydride elimination, releasing alkyl ligands and forming gold(III)-hydride intermediates that could be quickly converted into bioactive [AuIII -S] adducts; meanwhile, the remaining alkylgold(III) complexes can photo-catalytically reduce [AuIII -S] into more bioactive AuI species. Such photo-reactivities make it possible to functionalize gold complexes on the auxiliary alkyl ligands without attenuating the metal-biomacromolecule interactions. As a result, the gold(III) complexes containing glucose-functionalized alkyl ligands displayed efficient and tumor-selective uptake; notably, after one- or two-photon activation, the complexes exhibited high thioredoxin reductase (TrxR) inhibition, potent cytotoxicity, and strong antiangiogenesis and antitumor activities in vivo.
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