TY - JOUR
T1 - Mechanism of hydrolysis of a thiazolium ion
T2 - General acid-base catalysis of the breakdown of the tetrahedral addition intermediate
AU - Washabaugh, Michael W.
AU - Yang, Charles C.
AU - Stivers, James T.
AU - Lee, Kyung Sang
N1 - Funding Information:
We are grateful to John W. Bunting, Gordon A. Hamilton, Richard L. Schowen. helpful comments and William P. Jencks for advice, encouragement, and communication work from his laboratory. NMR studies were performed in the Biophysics NMR Hopkins University, which was established by a grant from the National Institutes 27512).
Funding Information:
’ Dedicated to the memory of Roger M. Herriott (1908-1992) who had an enduring interest in the history of science, the communication of ideas, and the chemical nature of life. This research was supported in part by grants from the National Institutes of Health (GM 42878), the American Cancer Society (PF-2669, JFRA-213), and a Biomedical Research Support Grant to Johns Hopkins University (2S07RR05445). Support was provided for J.T.S. and K.S.L. by training grants from the National Institute of Environmental Health Sciences (ST32ES07141) and National Cancer Institute (5T32CA09548), respectively. 2 To whom correspondence should
PY - 1992/12
Y1 - 1992/12
N2 - Rate constants in the pH range 3-9 for formation of the enethiolate product upon hydrolysis of 3,4-dimethylthiazolium ion, a model for the coenzyme thiamin, have been determined by irreversible iodination of the enethiolate at 25°C and ionic strength 1.0 m in aqueous solution. It is concluded that the rate-limiting step for hydrolysis of 3,4-dimethylthiazolium ion in the pH range 3-11 is breakdown of the neutral tetrahedral addition intermediate (T0) to product: general acid catalysis for enethiolate formation is observed and is inconsistent with rate-limiting formation of T0; buffer catalysis results provide no evidence for a change in rate-limiting step. Brønsted values are α = 0.53 for general acid and β = 0.31 for general base catalysis of the formation of the hydrolysis product by oxygen-containing buffers and primary amines: nucleophilic attack of the buffer bases has been ruled out. Catalysis by buffer acids is formulated as concerted general acid catalysis of the departure of the enethiol from T0. The buffer base- and water-catalyzed reactions are formulated as concerted general base catalysis of the expulsion of the enethiolate from T0. It is suggested that these mechanisms are general for hydrolysis reactions of 3-substituted-4-methylthiazolium ions where the substituent on the nitrogen atom of the thiazolium ring is not an intramolecular nucleophilic catalyst.
AB - Rate constants in the pH range 3-9 for formation of the enethiolate product upon hydrolysis of 3,4-dimethylthiazolium ion, a model for the coenzyme thiamin, have been determined by irreversible iodination of the enethiolate at 25°C and ionic strength 1.0 m in aqueous solution. It is concluded that the rate-limiting step for hydrolysis of 3,4-dimethylthiazolium ion in the pH range 3-11 is breakdown of the neutral tetrahedral addition intermediate (T0) to product: general acid catalysis for enethiolate formation is observed and is inconsistent with rate-limiting formation of T0; buffer catalysis results provide no evidence for a change in rate-limiting step. Brønsted values are α = 0.53 for general acid and β = 0.31 for general base catalysis of the formation of the hydrolysis product by oxygen-containing buffers and primary amines: nucleophilic attack of the buffer bases has been ruled out. Catalysis by buffer acids is formulated as concerted general acid catalysis of the departure of the enethiol from T0. The buffer base- and water-catalyzed reactions are formulated as concerted general base catalysis of the expulsion of the enethiolate from T0. It is suggested that these mechanisms are general for hydrolysis reactions of 3-substituted-4-methylthiazolium ions where the substituent on the nitrogen atom of the thiazolium ring is not an intramolecular nucleophilic catalyst.
UR - http://www.scopus.com/inward/record.url?scp=0039621913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0039621913&partnerID=8YFLogxK
U2 - 10.1016/0045-2068(92)90040-A
DO - 10.1016/0045-2068(92)90040-A
M3 - Article
AN - SCOPUS:0039621913
SN - 0045-2068
VL - 20
SP - 296
EP - 312
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
IS - 4
ER -