56269-39-7Relevant articles and documents
Mechanisms of Acid-Catalyzed Proton Exchange in N-Methyl Amides
Perrin, Charles L.,Arrhenius, Gloria M. L.
, p. 6693 - 6696 (1982)
Kinetics of acid-catalyzed proton exchange in an extensive series of N-methyl amides, RCONHCH3, were followed by NMR line-shape analysis in aqueous solution.Electron-withdrawing substituents retard the reaction, but the only good correlation is between log kH+ for substituted N-methyl acetamides and the pKa of the corresponding RCOOH.The correlation shows a change in slope, from 0.43 for amides with electron-withdrawing substituents to ca. 1.84 for other amides.This change is taken as evidence for a changeover from the imidic acid mechanism to the N-protonation mechanism.In particular, it is concluded that peptides and proteins represent amides with electron-withdrawing substituents, so that the NH protons of their backbone exchange predominantly via the imidic acid.The difference in slopes and the changeover in mechanism, as well as the comparison between primary and secondary amides, are rationalized in terms of substituent effects and transition-state structures.
Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes depends on the structure of the acyl group: Kinetic and product studies
Smith,Schmidt,Czerwinski,Taneyhill,Snyder,Kline,Michejda,Smith Jr.
, p. 466 - 475 (2007/10/03)
The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism.
