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Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors
Cobalt(III) Schiff base complexes ([Co(acacen)(L)2]+, where L = NH3) inhibit histidine-containing proteins through dissociative exchange of the labile axial ligands (L). This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibi...
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| Published in: | Inorganic chemistry 2015-09, Vol.54 (18), p.9066-9074 |
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| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-a486t-c675a18827a15ff03a60e8b86c1cdf37567d14d6127d31676ae6d7ad620756683 |
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| cites | cdi_FETCH-LOGICAL-a486t-c675a18827a15ff03a60e8b86c1cdf37567d14d6127d31676ae6d7ad620756683 |
| container_end_page | 9074 |
| container_issue | 18 |
| container_start_page | 9066 |
| container_title | Inorganic chemistry |
| container_volume | 54 |
| creator | Heffern, Marie C Reichova, Viktorie Coomes, Joseph L Harney, Allison S Bajema, Elizabeth A Meade, Thomas J |
| description | Cobalt(III) Schiff base complexes ([Co(acacen)(L)2]+, where L = NH3) inhibit histidine-containing proteins through dissociative exchange of the labile axial ligands (L). This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibitors that are activated by external triggers such as light irradiation. We sought to investigate ligand exchange dynamics to design a Co(III) complex that is substitutionally inert under normal physiological conditions for selective activation. Fluorescent imidazoles (C3Im) were prepared as axial ligands in [Co(acacen)(L)2]+ to produce complexes (CoC3Im) that could report on ligand exchange and, thus, complex stability. These fluorescent imidazole reporters guided the design of a new dinuclear Co(III) Schiff base complex containing bridging diimidazole ligands, which exhibits enhanced stability to ligand exchange with competing imidazoles and to hydrolysis within a biologically relevant pH range. These studies inform the design of biocompatible Co(III) Schiff base complexes that can be selectively activated for protein inhibition with spatial and temporal specificity. |
| doi_str_mv | 10.1021/acs.inorgchem.5b01415 |
| format | article |
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This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibitors that are activated by external triggers such as light irradiation. We sought to investigate ligand exchange dynamics to design a Co(III) complex that is substitutionally inert under normal physiological conditions for selective activation. Fluorescent imidazoles (C3Im) were prepared as axial ligands in [Co(acacen)(L)2]+ to produce complexes (CoC3Im) that could report on ligand exchange and, thus, complex stability. These fluorescent imidazole reporters guided the design of a new dinuclear Co(III) Schiff base complex containing bridging diimidazole ligands, which exhibits enhanced stability to ligand exchange with competing imidazoles and to hydrolysis within a biologically relevant pH range. These studies inform the design of biocompatible Co(III) Schiff base complexes that can be selectively activated for protein inhibition with spatial and temporal specificity.</description><identifier>ISSN: 0020-1669</identifier><identifier>EISSN: 1520-510X</identifier><identifier>DOI: 10.1021/acs.inorgchem.5b01415</identifier><identifier>PMID: 26331337</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Activated ; Cobalt ; Coordination Complexes - chemical synthesis ; Coordination Complexes - pharmacology ; Dynamic tests ; Exchange ; Fluorescence ; Fluorescent Dyes - chemical synthesis ; Fluorescent Dyes - pharmacology ; Imidazole ; Imidazoles - chemical synthesis ; Ligands ; Oligopeptides - antagonists & inhibitors ; Proteins ; Schiff bases ; Schiff Bases - chemical synthesis ; Schiff Bases - pharmacology</subject><ispartof>Inorganic chemistry, 2015-09, Vol.54 (18), p.9066-9074</ispartof><rights>Copyright © 2015 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a486t-c675a18827a15ff03a60e8b86c1cdf37567d14d6127d31676ae6d7ad620756683</citedby><cites>FETCH-LOGICAL-a486t-c675a18827a15ff03a60e8b86c1cdf37567d14d6127d31676ae6d7ad620756683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26331337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heffern, Marie C</creatorcontrib><creatorcontrib>Reichova, Viktorie</creatorcontrib><creatorcontrib>Coomes, Joseph L</creatorcontrib><creatorcontrib>Harney, Allison S</creatorcontrib><creatorcontrib>Bajema, Elizabeth A</creatorcontrib><creatorcontrib>Meade, Thomas J</creatorcontrib><title>Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors</title><title>Inorganic chemistry</title><addtitle>Inorg. Chem</addtitle><description>Cobalt(III) Schiff base complexes ([Co(acacen)(L)2]+, where L = NH3) inhibit histidine-containing proteins through dissociative exchange of the labile axial ligands (L). This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibitors that are activated by external triggers such as light irradiation. We sought to investigate ligand exchange dynamics to design a Co(III) complex that is substitutionally inert under normal physiological conditions for selective activation. Fluorescent imidazoles (C3Im) were prepared as axial ligands in [Co(acacen)(L)2]+ to produce complexes (CoC3Im) that could report on ligand exchange and, thus, complex stability. These fluorescent imidazole reporters guided the design of a new dinuclear Co(III) Schiff base complex containing bridging diimidazole ligands, which exhibits enhanced stability to ligand exchange with competing imidazoles and to hydrolysis within a biologically relevant pH range. These studies inform the design of biocompatible Co(III) Schiff base complexes that can be selectively activated for protein inhibition with spatial and temporal specificity.</description><subject>Activated</subject><subject>Cobalt</subject><subject>Coordination Complexes - chemical synthesis</subject><subject>Coordination Complexes - pharmacology</subject><subject>Dynamic tests</subject><subject>Exchange</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes - chemical synthesis</subject><subject>Fluorescent Dyes - pharmacology</subject><subject>Imidazole</subject><subject>Imidazoles - chemical synthesis</subject><subject>Ligands</subject><subject>Oligopeptides - antagonists & inhibitors</subject><subject>Proteins</subject><subject>Schiff bases</subject><subject>Schiff Bases - chemical synthesis</subject><subject>Schiff Bases - pharmacology</subject><issn>0020-1669</issn><issn>1520-510X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNkVFr2zAUhcXYWNNsP2HDj-lDUl3JluyXQhraxhDYYBnsTciynKjYUirZpf33VUga2qfuSRfd7xzuvQehH4BngAlcShVmxjq_UVvdzbIKQwrZJzSCjOBpBvjfZzTCONbAWHGGzkO4xxgXNGVf0RlhlAKlfISW68Eau0kWrpJtPynL8iL5o7amaZJrGXT873atftIhkSGZq948yl7XyW_vem1sUtqtqUzvfPiGvjSyDfr78R2jv7c368Vyuvp1Vy7mq6lMc9ZPFeOZhDwnXELWNJhKhnVe5UyBqhvKM8ZrSGsGhNcUGGdSs5rLmhEceyynY3R18N0NVadrpW3vZSt23nTSPwsnjXjfsWYrNu5RpIzmJC4-RpOjgXcPgw696ExQum2l1W4IAnhBSZGSlP8HCnEmTAsc0eyAKu9C8Lo5TQRY7AMTMTBxCkwcA4u6n2_XOaleE4oAHIC9_t4N3sbrfmD6Av0mpWA</recordid><startdate>20150921</startdate><enddate>20150921</enddate><creator>Heffern, Marie C</creator><creator>Reichova, Viktorie</creator><creator>Coomes, Joseph L</creator><creator>Harney, Allison S</creator><creator>Bajema, Elizabeth A</creator><creator>Meade, Thomas J</creator><general>American Chemical Society</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>7X8</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>5PM</scope></search><sort><creationdate>20150921</creationdate><title>Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors</title><author>Heffern, Marie C ; Reichova, Viktorie ; Coomes, Joseph L ; Harney, Allison S ; Bajema, Elizabeth A ; Meade, Thomas J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a486t-c675a18827a15ff03a60e8b86c1cdf37567d14d6127d31676ae6d7ad620756683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Activated</topic><topic>Cobalt</topic><topic>Coordination Complexes - chemical synthesis</topic><topic>Coordination Complexes - pharmacology</topic><topic>Dynamic tests</topic><topic>Exchange</topic><topic>Fluorescence</topic><topic>Fluorescent Dyes - chemical synthesis</topic><topic>Fluorescent Dyes - pharmacology</topic><topic>Imidazole</topic><topic>Imidazoles - chemical synthesis</topic><topic>Ligands</topic><topic>Oligopeptides - antagonists & inhibitors</topic><topic>Proteins</topic><topic>Schiff bases</topic><topic>Schiff Bases - chemical synthesis</topic><topic>Schiff Bases - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heffern, Marie C</creatorcontrib><creatorcontrib>Reichova, Viktorie</creatorcontrib><creatorcontrib>Coomes, Joseph L</creatorcontrib><creatorcontrib>Harney, Allison S</creatorcontrib><creatorcontrib>Bajema, Elizabeth A</creatorcontrib><creatorcontrib>Meade, Thomas J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heffern, Marie C</au><au>Reichova, Viktorie</au><au>Coomes, Joseph L</au><au>Harney, Allison S</au><au>Bajema, Elizabeth A</au><au>Meade, Thomas J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors</atitle><jtitle>Inorganic chemistry</jtitle><addtitle>Inorg. Chem</addtitle><date>2015-09-21</date><risdate>2015</risdate><volume>54</volume><issue>18</issue><spage>9066</spage><epage>9074</epage><pages>9066-9074</pages><issn>0020-1669</issn><eissn>1520-510X</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>These authors contributed equally to this work.</notes><abstract>Cobalt(III) Schiff base complexes ([Co(acacen)(L)2]+, where L = NH3) inhibit histidine-containing proteins through dissociative exchange of the labile axial ligands (L). This work investigates axial ligand exchange dynamics of [Co(acacen)(L)2]+ complexes toward the development of protein inhibitors that are activated by external triggers such as light irradiation. We sought to investigate ligand exchange dynamics to design a Co(III) complex that is substitutionally inert under normal physiological conditions for selective activation. Fluorescent imidazoles (C3Im) were prepared as axial ligands in [Co(acacen)(L)2]+ to produce complexes (CoC3Im) that could report on ligand exchange and, thus, complex stability. These fluorescent imidazole reporters guided the design of a new dinuclear Co(III) Schiff base complex containing bridging diimidazole ligands, which exhibits enhanced stability to ligand exchange with competing imidazoles and to hydrolysis within a biologically relevant pH range. These studies inform the design of biocompatible Co(III) Schiff base complexes that can be selectively activated for protein inhibition with spatial and temporal specificity.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26331337</pmid><doi>10.1021/acs.inorgchem.5b01415</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Activated Cobalt Coordination Complexes - chemical synthesis Coordination Complexes - pharmacology Dynamic tests Exchange Fluorescence Fluorescent Dyes - chemical synthesis Fluorescent Dyes - pharmacology Imidazole Imidazoles - chemical synthesis Ligands Oligopeptides - antagonists & inhibitors Proteins Schiff bases Schiff Bases - chemical synthesis Schiff Bases - pharmacology |
| title | Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors |
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