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Nucleophilic reactivity of thiolate, hydroxide, and phenolate ions toward a model O 2 ‐arylated diazeniumdiolate prodrug in aqueous and cationic surfactant media
Author(s) -
Ning Matthew S.,
Price Stacy E.,
Ta Jackie,
Davies Keith M.
Publication year - 2010
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1607
Subject(s) - chemistry , thiolysis , nucleophile , hydroxide , aqueous solution , cationic polymerization , medicinal chemistry , reaction rate constant , hydrolysis , nucleophilic substitution , inorganic chemistry , prodrug , organic chemistry , catalysis , kinetics , polyphenol , physics , biochemistry , proanthocyanidin , quantum mechanics , antioxidant
The kinetics of aromatic nucleophilic substitution of the nitric oxide‐generating diazeniumdiolate ion, DEA/NO, by thiols ( L ‐glutathione, L ‐cysteine, DL ‐homocysteine, 1‐propanethiol, 2‐mercaptoethanol, and sodium thioglycolate) from the prodrug, DNP‐DEA/NO, has been examined in aqueous solution and in solutions of cationic DOTAP vesicles. Second‐order rate constants in buffered aqueous solutions ( k RS ‐ = 3.48–30.9 M −1 s −1 ; 30 °C) gave a linear Brønsted plot ( β nuc = 0.414 ± 0.068) consistent with the rate‐limiting S N Ar nucleophilic attack by thiolate ions. Cationic DOTAP vesicles catalyze the thiolysis reactions with rate enhancements between 11 and 486‐fold in Tris‐HCl buffered solutions at pH 7.4. The maximum rate increase was obtained with thioglycolate ion. Thiolysis data are compared to data for nucleophilic displacement by phenolate ( k PhO ‐ = 0.114 M −1 s −1 ) and hydroxide ( k OH ‐ = 1.82 × 10 −2 M −1 s −1 , 37 °C) ions. The base hydrolysis reaction is accelerated by CTAB micelles and DODAC vesicles, with the vesicles being ca 3‐fold more effective as catalysts. Analysis of the data using pseudo‐phase ion‐exchange (PIE) formalism implies that the rate enhancement of the thiolysis and base hydrolysis reactions is primarily due to reactant concentration in the surfactant pseudo‐phase. Copyright © 2009 John Wiley & Sons, Ltd.