Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions
- 5 January 2021
- journal article
- review article
- Published by American Chemical Society (ACS) in Chemical Reviews
- Vol. 121 (12), 6850-6914
- https://doi.org/10.1021/acs.chemrev.0c01013
Abstract
Reactions that occur under physiological conditions find diverse uses in the chemical and biological sciences. However, the limitations that biological systems place on chemical reactions restrict the number of such bioorthogonal reactions. A profound understanding of the mechanistic principles and structure–reactivity trends of these transformations is therefore critical to access new and improved versions of bioorthogonal chemistry. The present article reviews the mechanisms and substituent effects of some of the principal metal-free bioorthogonal reactions based on inverse-electron demand Diels–Alder reactions, 1,3-dipolar cycloadditions, and the Staudinger reaction. Mechanisms of modified versions that link these reactions to a dissociative step are further discussed. The presented summary is anticipated to aid the advancement of bioorthogonal chemistry.Keywords
Funding Information
- Division of Chemistry (2004010)
- University of Utah
- American Foundation for Pharmaceutical Education
This publication has 432 references indexed in Scilit:
- Metabolic Glycan Imaging by Isonitrile–Tetrazine Click ChemistryChemBioChem, 2013
- Thiacycloalkynes for Copper‐Free Click ChemistryAngewandte Chemie-International Edition, 2012
- Copper‐Catalyzed Azide–Alkyne Click Chemistry for BioconjugationCurrent Protocols in Chemical Biology, 2011
- From Mechanism to Mouse: A Tale of Two Bioorthogonal ReactionsAccounts of Chemical Research, 2011
- Readily Accessible Bicyclononynes for Bioorthogonal Labeling and Three‐Dimensional Imaging of Living CellsAngewandte Chemie-International Edition, 2010
- Fast and Sensitive Pretargeted Labeling of Cancer Cells through a Tetrazine/trans‐Cyclooctene CycloadditionAngewandte Chemie-International Edition, 2009
- Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of FunctionalityAngewandte Chemie-International Edition, 2009
- A Phosphine‐Mediated Conversion of Azides into Diazo CompoundsAngewandte Chemie-International Edition, 2009
- Coulombic effects on the traceless Staudinger ligation in waterBioorganic & Medicinal Chemistry, 2009
- Visualizing Metabolically Labeled Glycoconjugates of Living Cells by Copper‐Free and Fast Huisgen CycloadditionsAngewandte Chemie-International Edition, 2008