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Observation and Kinetic Characterization of Transient Schiff Base Intermediates by CEST NMR Spectroscopy
Author(s) -
Ramanujam Venkatraman,
Charlier Cyril,
Bax Ad
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908416
Subject(s) - chemistry , schiff base , aldehyde , hemiaminal , adduct , nuclear magnetic resonance spectroscopy , reaction intermediate , organic chemistry , stereochemistry , catalysis
In aqueous solution, many biochemical reaction pathways involve reaction of an aldehyde with an amine, which progresses through generally unstable, hydrated and dehydrated, Schiff base intermediates that often are unobservable by conventional NMR. There are 4 states in the relevant equilibrium: 1) gem‐diol, 2) aldehyde, 3) hemiaminal, and 4) Schiff base. For the reaction between protein amino groups and DOPAL, a highly toxic metabolite of dopamine, the 1 H resonances of both the hemiaminal and the dehydrated Schiff base can be observed by CEST NMR, even when their populations fall below 0.1 %. CEST NMR reveals the quantitative exchange kinetics between reactants and Schiff base intermediates, explaining why the Schiff base NMR signals are rarely observed. The reactivity of DOPAL with N α ‐amino groups is greater than with lysine N ϵ ‐amines and, in the presence of O 2 , both types of Schiff base DOPAL–peptide intermediates rapidly react with free DOPAL to irreversibly form dicatechol pyrrole adducts.