Cyclometalated Gold(III)-Hydride Complexes Exhibit Visible Light-Induced Thiol Reactivity and Act as Potent Photo-Activated Anti-Cancer Agents.

Hejiang Luo, Bei Cao, Albert S C Chan, Raymond Wai-Yin Sun, Taotao Zou

Angewandte Chemie (International ed. in English) 2020 Jun 26

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The specific gold-sulfur binding interaction renders gold complexes as promising anti-cancer agents that can potentially overcome cisplatin resistance; while their unbiased binding towards non-tumoral off-target thiol-proteins has posed a big hurdle to clinical application. Herein we report that cyclometalated gold(III) complexes bearing hydride ligands are highly stable towards thiols in the dark but can efficiently dissociate the auxiliary hydride moiety and generate a gold-thiol adduct when excited with visible light. In consequence, the photo-activated gold(III) complexes potently inhibited thioredoxin reductase in association with up to >400-fold increment of photocytotoxicity (vs. dark condition) without deactivation by serum albumin and along with strong anti-angiogenesis activity in zebrafish embryos. Importantly, the gold(III)-hydride complexes could be activated by two-photon laser irradiation at the phototherapeutic window as effectively as blue-light irradiation. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Hejiang Luo, Bei Cao, Albert S C Chan, Raymond Wai-Yin Sun, Taotao Zou. Cyclometalated Gold(III)-Hydride Complexes Exhibit Visible Light-Induced Thiol Reactivity and Act as Potent Photo-Activated Anti-Cancer Agents. Angewandte Chemie (International ed. in English). 2020 Jun 26;59(27):11046-11052