Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

Exploring the charged nature of supramolecular micelles based on p-sulfonatocalix[6]arene and dodecyltrimethylammonium bromide.

The aggregation of supramolecular amphiphiles formed from hexamethylated p-sulfonatocalix[6]arene (SC6HM) and dodecyltrimethylammonium bromide (C12TAB) was studied by capillary electrophoresis experiments and by kinetic probes. The hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC) was used to investigate the micropolarity of the micellar aggregates and their ability to solubilize and stabilize labile organic compounds against hydrolysis. Further insights were obtained using a more sophisticated kinetic probe: the basic hydrolysis of p-nitrophenylvalerate (NPV). This probe provides information on the ionic composition of the micellar interface and on the potential of the aggregates to be used as nanoreactors. The results obtained revealed that the charge of the micellar aggregates can be tuned from anionic to cationic through the adjustment of the C12TAB : SC6HM molar ratio and confirmed that these micelles have good solubilization properties. On the other hand, the kinetics of the p-nitrophenylvalerate basic hydrolysis suggest that, in the concentration range comprised between the first and second CMCs, Br(-) anions do not take part in the micellar structure.