Ionization and Intramolecular Reactions of N,N-Bis- and N,N-Bismaleamic Acids. An Enzyme Model

Article abstract of DOI:10.1021/jo00335a006

N,N-Bis<(2-pyridyl)ethyl>maleamic acid (1) and N,N-bis<(2-pyridyl)methyl>maleamic acid (2) underwent exclusive amide hydrolysis and intramolecular Michael-type addition, respectively.The pH profile of the pseudo-first-order rate constant for the reaction of 1 was a simple descending sigmoid inflecting at the pK_a of the carboxyl group.The pH profile of 2 was a composite of two bell-shaped curves which disclosed the abnormally low pK_a's of the carboxyl group and one of the two pyridinium groups.The change in the reaction path and the abnormal pK_a's observed withthe structural variation in maleamic acid derivatives suggest that the change in enzyme specificity and the perturbed pK_a's of the active site functional groups can be achieved with a relatively loose geometry of the enzyme-substrate complex.The failure to observe the metal ion catalysis of the amide hydrolysis of 1 and 2 indicates that the metal complexation of the compounds is inefficient.