title: A Bioorthogonal Reaction of N-Oxide and Boron Reagents.
abstract: The development of bioorthogonal reactions has classically focused on bond-forming ligation reactions. In this report, we seek to expand the functional repertoire of such transformations by introducing a new bond-cleaving reaction between N-oxide and boron reagents. The reaction features a large dynamic range of reactivity, showcasing second-order rate constants as high as 2.3×10(3)  M(-1)  s(-1) using diboron reaction partners. Diboron reagents display minimal cell toxicity at millimolar concentrations, penetrate cell membranes, and effectively reduce N-oxides inside mammalian cells. This new bioorthogonal process based on miniscule components is thus well-suited for activating molecules within cells under chemical control. Furthermore, we demonstrate that the metabolic diversity of nature enables the use of naturally occurring functional groups that display inherent biocompatibility alongside abiotic components for organism-specific applications.
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, Stanford University, 380 Roth Way, Stanford, CA 94305 (USA).
authors.forename: Justin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, Stanford University, 380 Roth Way, Stanford, CA 94305 (USA). bertozzi@stanford.edu.
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D001895:Boron / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D010087:Oxides; D001895:Boron
keywords: N-oxides; bioorthogonal chemistry; diboron reagents; small-molecule activation; uncaging