Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems
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 transmetalla...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2021-02, Vol.60 (8), p.4133-4141 |
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| creator | Long, Yan Cao, Bei Xiong, Xiaolin Chan, Albert S. C. Sun, Raymond Wai‐Yin Zou, Taotao |
| description | 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 1H 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.
A novel bioorthogonal activation approach based on Pd(II)‐mediated transmetallation was developed to controllably activate stable organometallic NHC–gold(I)–phenylacetylide complex. The gold(I) complex, upon transmetallation activation, can catalyze alkyne π‐bond activations and can meanwhile potently inhibit thioredoxin reductase and induce cytotoxicity towards cancer cells in vitro and in vivo with high spatiotemporal selectivity. |
| doi_str_mv | 10.1002/anie.202013366 |
| format | Article |
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A novel bioorthogonal activation approach based on Pd(II)‐mediated transmetallation was developed to controllably activate stable organometallic NHC–gold(I)–phenylacetylide complex. The gold(I) complex, upon transmetallation activation, can catalyze alkyne π‐bond activations and can meanwhile potently inhibit thioredoxin reductase and induce cytotoxicity towards cancer cells in vitro and in vivo with high spatiotemporal selectivity.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.202013366</identifier><identifier>PMID: 33151608</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Alkynes - chemistry ; Angiogenesis ; Animals ; anti-cancer ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - pharmacology ; bioorthogonal activation ; Cancer ; Catalysis ; Cell Line, Tumor ; Cell proliferation ; Cell Survival - drug effects ; Coordination Complexes - chemistry ; Coordination Complexes - metabolism ; Coordination Complexes - pharmacology ; Coordination compounds ; Danio rerio ; Density Functional Theory ; Embryo, Nonmammalian - chemistry ; Embryo, Nonmammalian - metabolism ; Fluorescence ; Gold - chemistry ; gold medicine ; Humans ; in-cell catalysis ; Metal complexes ; Methane - analogs & derivatives ; Methane - chemistry ; NMR ; Nuclear magnetic resonance ; Optical Imaging ; Palladium ; Palladium - chemistry ; Reductases ; thiol reactivity ; Thiols ; Thioredoxin ; Zebrafish ; Zebrafish - growth & development ; Zebrafish - metabolism</subject><ispartof>Angewandte Chemie International Edition, 2021-02, Vol.60 (8), p.4133-4141</ispartof><rights>2020 Wiley‐VCH GmbH</rights><rights>2020 Wiley-VCH GmbH.</rights><rights>2021 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4106-3a3e6214880fd32d6f46d08cc8bf51669c17cf4107a25aac66971d780779fe233</citedby><cites>FETCH-LOGICAL-c4106-3a3e6214880fd32d6f46d08cc8bf51669c17cf4107a25aac66971d780779fe233</cites><orcidid>0000-0001-9129-4398</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.202013366$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.202013366$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33151608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Long, Yan</creatorcontrib><creatorcontrib>Cao, Bei</creatorcontrib><creatorcontrib>Xiong, Xiaolin</creatorcontrib><creatorcontrib>Chan, Albert S. C.</creatorcontrib><creatorcontrib>Sun, Raymond Wai‐Yin</creatorcontrib><creatorcontrib>Zou, Taotao</creatorcontrib><title>Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>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 1H 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.
A novel bioorthogonal activation approach based on Pd(II)‐mediated transmetallation was developed to controllably activate stable organometallic NHC–gold(I)–phenylacetylide complex. The gold(I) complex, upon transmetallation activation, can catalyze alkyne π‐bond activations and can meanwhile potently inhibit thioredoxin reductase and induce cytotoxicity towards cancer cells in vitro and in vivo with high spatiotemporal selectivity.</description><subject>Alkynes - chemistry</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>anti-cancer</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>bioorthogonal activation</subject><subject>Cancer</subject><subject>Catalysis</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Survival - drug effects</subject><subject>Coordination Complexes - chemistry</subject><subject>Coordination Complexes - metabolism</subject><subject>Coordination Complexes - pharmacology</subject><subject>Coordination compounds</subject><subject>Danio rerio</subject><subject>Density Functional Theory</subject><subject>Embryo, Nonmammalian - chemistry</subject><subject>Embryo, Nonmammalian - metabolism</subject><subject>Fluorescence</subject><subject>Gold - chemistry</subject><subject>gold medicine</subject><subject>Humans</subject><subject>in-cell catalysis</subject><subject>Metal complexes</subject><subject>Methane - analogs & derivatives</subject><subject>Methane - chemistry</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Optical Imaging</subject><subject>Palladium</subject><subject>Palladium - chemistry</subject><subject>Reductases</subject><subject>thiol reactivity</subject><subject>Thiols</subject><subject>Thioredoxin</subject><subject>Zebrafish</subject><subject>Zebrafish - growth & development</subject><subject>Zebrafish - metabolism</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0btOwzAUBmALgWi5rIwoEgsMKb4ktjuWcKtUwQDMkXGc4iqxi-0A3XgEnpEnwVWhSCxMto4__zo6B4ADBAcIQnwqjFYDDDFEhFC6AfooxygljJHNeM8ISRnPUQ_seD-LnnNIt0GPEJQjCnkfhDNtrQtPdmqNaJKRDPpFBG1NYuvkvIulQgTRLIKWiTBVMjJBf75_FMJI5VZcB638kt-6qTAxqKmOxydJYdt5o97ikzbJJDIzTe4WPqjW74GtWjRe7X-fu-Dh8uK-uE4nt1fjYjRJZYYgTYkgimKUxabriuCK1hmtIJeSP9axfTqUiMk6UiZwLoSMFYYqxiFjw1phQnbB8Sp37uxzp3woW-2lahphlO18ibOcDRnkeRbp0R86s52LI1kqznPM4uyiGqyUdNZ7p-py7nQr3KJEsFzuo1zuo1zvI344_I7tHltVrfnPAiIYrsCrbtTin7hydDO--A3_AqQ1lyw</recordid><startdate>20210219</startdate><enddate>20210219</enddate><creator>Long, Yan</creator><creator>Cao, Bei</creator><creator>Xiong, Xiaolin</creator><creator>Chan, Albert S. C.</creator><creator>Sun, Raymond Wai‐Yin</creator><creator>Zou, Taotao</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9129-4398</orcidid></search><sort><creationdate>20210219</creationdate><title>Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems</title><author>Long, Yan ; Cao, Bei ; Xiong, Xiaolin ; Chan, Albert S. C. ; Sun, Raymond Wai‐Yin ; Zou, Taotao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4106-3a3e6214880fd32d6f46d08cc8bf51669c17cf4107a25aac66971d780779fe233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alkynes - chemistry</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>anti-cancer</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>bioorthogonal activation</topic><topic>Cancer</topic><topic>Catalysis</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Survival - drug effects</topic><topic>Coordination Complexes - chemistry</topic><topic>Coordination Complexes - metabolism</topic><topic>Coordination Complexes - pharmacology</topic><topic>Coordination compounds</topic><topic>Danio rerio</topic><topic>Density Functional Theory</topic><topic>Embryo, Nonmammalian - chemistry</topic><topic>Embryo, Nonmammalian - metabolism</topic><topic>Fluorescence</topic><topic>Gold - chemistry</topic><topic>gold medicine</topic><topic>Humans</topic><topic>in-cell catalysis</topic><topic>Metal complexes</topic><topic>Methane - analogs & derivatives</topic><topic>Methane - chemistry</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Optical Imaging</topic><topic>Palladium</topic><topic>Palladium - chemistry</topic><topic>Reductases</topic><topic>thiol reactivity</topic><topic>Thiols</topic><topic>Thioredoxin</topic><topic>Zebrafish</topic><topic>Zebrafish - growth & development</topic><topic>Zebrafish - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Long, Yan</creatorcontrib><creatorcontrib>Cao, Bei</creatorcontrib><creatorcontrib>Xiong, Xiaolin</creatorcontrib><creatorcontrib>Chan, Albert S. C.</creatorcontrib><creatorcontrib>Sun, Raymond Wai‐Yin</creatorcontrib><creatorcontrib>Zou, Taotao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Long, Yan</au><au>Cao, Bei</au><au>Xiong, Xiaolin</au><au>Chan, Albert S. C.</au><au>Sun, Raymond Wai‐Yin</au><au>Zou, Taotao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2021-02-19</date><risdate>2021</risdate><volume>60</volume><issue>8</issue><spage>4133</spage><epage>4141</epage><pages>4133-4141</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><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 (1 a) in vitro and in vivo. A combination of 1H 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.
A novel bioorthogonal activation approach based on Pd(II)‐mediated transmetallation was developed to controllably activate stable organometallic NHC–gold(I)–phenylacetylide complex. The gold(I) complex, upon transmetallation activation, can catalyze alkyne π‐bond activations and can meanwhile potently inhibit thioredoxin reductase and induce cytotoxicity towards cancer cells in vitro and in vivo with high spatiotemporal selectivity.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33151608</pmid><doi>10.1002/anie.202013366</doi><tpages>9</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0001-9129-4398</orcidid></addata></record> |
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| subjects | Alkynes - chemistry Angiogenesis Animals anti-cancer Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - metabolism Antineoplastic Agents - pharmacology bioorthogonal activation Cancer Catalysis Cell Line, Tumor Cell proliferation Cell Survival - drug effects Coordination Complexes - chemistry Coordination Complexes - metabolism Coordination Complexes - pharmacology Coordination compounds Danio rerio Density Functional Theory Embryo, Nonmammalian - chemistry Embryo, Nonmammalian - metabolism Fluorescence Gold - chemistry gold medicine Humans in-cell catalysis Metal complexes Methane - analogs & derivatives Methane - chemistry NMR Nuclear magnetic resonance Optical Imaging Palladium Palladium - chemistry Reductases thiol reactivity Thiols Thioredoxin Zebrafish Zebrafish - growth & development Zebrafish - metabolism |
| title | Bioorthogonal Activation of Dual Catalytic and Anti‐Cancer Activities of Organogold(I) Complexes in Living Systems |
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