Ring Substituent Effects on the Thiol Addition and Hydrolysis Reactions of N-Arylmaleimides

详细信息    查看全文

• 作者：Yingche Chen ; Kelvin Tsao ; 脡lise De Francesco ; Jeffrey W. Keillor
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：December 18, 2015
• 年：2015
• 卷：80
• 期：24
• 页码：12182-12192
• 全文大小：568K
• ISSN：1520-6904

文摘

Maleimide groups are used extensively in bioconjugation reactions, but limited kinetic information is available regarding their thiol addition and hydrolysis reactions. We prepared a series of fluorogenic coumarin maleimide derivatives that differ by the substituent on their maleimide C鈺怌 bond. Fluorescence-based kinetic studies of the reaction with 尾-mercaptoethanol (BME) yielded the second-order rate constants (k₂), while pH鈥搑ate studies from pH 7 to 9 gave base-catalyzed hydrolysis rate constants (k_OH). Linear free-energy relationships were studied through the correlation of log k₂ and log k_OH to both electronic (蟽⁺) and steric (E_s^norm) parameters of the C鈺怌 substituent. These correlations revealed the thiol addition reaction is primarily sensitive to the electronic effects, while steric effects dominate the hydrolysis reaction. These mechanistic studies provide the basis for the design of novel bioconjugation reactants or fluorogenic labeling agents.