Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.
Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.
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DOI：
10.1002/chem.201502077
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发表时间：
2015-10-12
期刊：
影响因子：
--
通讯作者：
Gao J
中科院分区：
文献类型：
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作者：
Bandyopadhyay A;Gao J
在生理条件下快速且可逆的生物正交反应在生物应用中具有很高的需求。在本文中，我们发现邻硼酸取代基使芳基酮在中性pH下与α-亲核试剂快速缀合。具体地说，发现2-乙酰基苯基硼酸及其衍生物与苯肼缀合的速率常数为102至103 M−1 s−1，与迄今为止已知的最快的生物正交缀合相当。11B-NMR分析揭示了不同程度的亚氨基硼酸盐形成的共轭物，其中亚胺氮与硼形成配价键。亚氨基硼酸盐的形成激活亚胺的水解和交换，使这些肟/腙共轭可逆和动态的生理条件下。亚氨基硼酸盐化学的快速和动态性质应该在生物学中找到广泛的应用。
Bioorthogonal reactions that are fast and reversible under physiologic conditions are in high demand for biological applications. Herein, we show that an ortho boronic acid substituent makes aryl ketones to rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 102 to 103 M−1 s−1, comparable to the fastest bioorthogonal conjugations known to date. 11B-NMR analysis reveals 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 physiologic conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology.