Bandyopadhyay Anupam, Gao Jianmin
Department of Chemistry, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467 (USA).
Chemistry. 2015 Oct 12;21(42):14748-52. doi: 10.1002/chem.201502077. Epub 2015 Aug 27.
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.
在生理条件下快速且可逆的生物正交反应在生物应用中需求很高。在此，研究表明邻硼酸取代基使芳基酮在中性pH下能与α-亲核试剂快速共轭。具体而言，发现2-乙酰基苯硼酸及其衍生物与苯肼共轭的速率常数为10²至10³ M⁻¹ s⁻¹，与迄今为止已知的最快生物正交共轭反应相当。¹¹B NMR分析揭示了共轭物中亚氨基硼酸酯形成的不同程度，其中亚胺氮与硼形成配位键。亚氨基硼酸酯的形成激活了亚胺进行水解和交换，使得这些肟/腙共轭反应在生理条件下具有可逆性和动态性。亚氨基硼酸酯化学的快速和动态特性应在生物学中有广泛应用。
