Premium
Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α‐Nucleophiles at Neutral pH
Author(s) -
Bandyopadhyay Anupam,
Gao Jianmin
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502077
Subject(s) - chemistry , nucleophile , conjugate , phenylhydrazine , conjugate acid , imine , oxime , bioorthogonal chemistry , substituent , boronic acid , aryl , hydrazone , combinatorial chemistry , medicinal chemistry , organic chemistry , photochemistry , catalysis , ion , mathematical analysis , alkyl , mathematics , click chemistry
Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α‐nucleophiles at neutral pH. Specifically, 2‐acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10 2 to 10 3 M −1 s −1 , comparable to the fastest bioorthogonal conjugations known to date. 11 B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology.