Origin of Orthogonality of Strain-Promoted Click Reactions
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Johannes A Wagner
- Davide Mercadante
- Ivana Nikic
- Edward A Lemke
- Frauke Graeter
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000360093700027&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/chem.201501727
- eISSN
- 1521-3765
- Externe Identifier
- Clarivate Analytics Document Solution ID: CP7UJ
- PubMed Identifier: 26178299
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 35
- Zeitschrift
- CHEMISTRY-A EUROPEAN JOURNAL
- Schlüsselwörter
- cycloaddition
- inverse electron demand
- Diels-Alder reaction
- density functional calculations
- orbital gap
- Paginierung
- 12431 - 12435
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Origin of Orthogonality of Strain-Promoted Click Reactions
- Sub types
- Article
- Ausgabe der Zeitschrift
- 21
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Site‐specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain‐promoted click‐type cycloaddition reactions of <jats:italic>n</jats:italic>‐propyl azide, 3‐benzyl tetrazine and 3‐benzyl‐6‐methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels–Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling.</jats:p>
- Autoren
- Johannes A Wagner
- Davide Mercadante
- Ivana Nikić
- Edward A Lemke
- Frauke Gräter
- DOI
- 10.1002/chem.201501727
- eISSN
- 1521-3765
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 35
- Zeitschrift
- Chemistry – A European Journal
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 12431 - 12435
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/chem.201501727
- Datum der Datenerfassung
- 2023
- Titel
- Origin of Orthogonality of Strain‐Promoted Click Reactions
- Ausgabe der Zeitschrift
- 21
Datenquelle: Crossref
- Abstract
- Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine and 3-benzyl-6-methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels-Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling.
- Addresses
- Heidelberg Institute for Theoretical Studies, 69118 Heidelberg (Germany), Fax: (+49) 6221-533-298.
- Autoren
- Johannes A Wagner
- Davide Mercadante
- Ivana Nikić
- Edward A Lemke
- Frauke Gräter
- DOI
- 10.1002/chem.201501727
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Identifier: 26178299
- PubMed Central ID: PMC4600239
- Funding acknowledgements
- DFG: Emmy Noether program
- Funded Access:
- DFG: SPP163
- Klaus Tschira Foundation:
- EMBO:
- Marie Curie programme FP7:
- Open access
- true
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 35
- Zeitschrift
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Open access status
- Open Access
- Paginierung
- 12431 - 12435
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2015
- Titel
- Origin of Orthogonality of Strain-Promoted Click Reactions.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 21
Files
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/chem.201501727 https://europepmc.org/articles/PMC4600239?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine and 3-benzyl-6-methyl tetrazine with cyclooctenes/ynes, in which we aim to address all relevant structural details of the reactants. Our calculations have included the obligatory handles used to attach the label and biomolecule as these can critically influence the stereochemistry and electron demand of the reaction. We systematically computed orbital gaps, activation and distortion energies using density functional theory and determined experimental rates for validation. Our results challenge the current paradigm of the inverse electron demand for this class of reactions. We found that the ubiquitous handles, when next to the triple bond of cyclooctynes, can switch the Diels-Alder type ligations to normal electron demand, a class we term as SPINEDAC reactions. Electron donating substituents on tetrazine can enhance normal demand but also increase distortion penalties. The presence and isomeric configuration of handles thus determine the reaction speed and regioselectivity. Our findings can be directly utilized in engineering genuine cycloaddition click chemistries for biological labeling.
- Autoren
- Johannes A Wagner
- Davide Mercadante
- Ivana Nikić
- Edward A Lemke
- Frauke Gräter
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26178299
- DOI
- 10.1002/chem.201501727
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Central ID: PMC4600239
- Ausgabe der Veröffentlichung
- 35
- Zeitschrift
- Chemistry
- Schlüsselwörter
- Diels-Alder reaction
- cycloaddition
- density functional calculations
- inverse electron demand
- orbital gap
- Sprache
- eng
- Country
- Germany
- Paginierung
- 12431 - 12435
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2016
- Titel
- Origin of Orthogonality of Strain-Promoted Click Reactions.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 21
Datenquelle: PubMed
- Beziehungen:
- Eigentum von