Ring Substituent Effects on the Thiol Addition and Hydrolysis Reactions of N-Arylmaleimides.
J Org Chem
; 80(24): 12182-92, 2015 Dec 18.
Article
in En
| MEDLINE
| ID: mdl-26595216
ABSTRACT
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 CâC bond. Fluorescence-based kinetic studies of the reaction with ß-mercaptoethanol (BME) yielded the second-order rate constants (k2), while pH-rate studies from pH 7 to 9 gave base-catalyzed hydrolysis rate constants (kOH). Linear free-energy relationships were studied through the correlation of log k2 and log kOH to both electronic (σ(+)) and steric (Es(norm)) parameters of the CâC 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
J Org Chem
Year:
2015
Document type:
Article
Affiliation country:
Canada