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1 H NMR spectroscopic identification of protonable sites in cryptolepines with C‐11 substituents containing two amino functionalities
Author(s) -
Lavrado João,
Paulo Alexandra,
Bichenkova Elena,
Douglas Kenneth T.,
Moreira Rui
Publication year - 2012
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.2873
Subject(s) - chemistry , potentiometric titration , dissociation constant , titration , acid dissociation constant , proton nmr , dissociation (chemistry) , carbon 13 nmr , stereochemistry , combinatorial chemistry , computational chemistry , organic chemistry , aqueous solution , ion , biochemistry , receptor
Knowledge of protonable sites and acid dissociation constants of cryptolepine derivatives having C‐11 substituents containing two amino functionalities is of great importance to the understanding of the mechanism of their antimalarial action, which may contribute to their further development as drug candidates. In this work, we applied 1 H NMR titration to investigate the acid–base characteristics of these polyprotic compounds in the pH range 3–13. We identified three acid–base equilibria with most acid dissociation constants (p K a *) being greater than 10.5, which prevented us from using the potentiometric method. Overall, 1 H NMR titration was sensitive and suitable for the determination of p K a values for these drug leads. Copyright © 2012 John Wiley & Sons, Ltd.