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Transition-state Acidities and the pH Dependence of Drug Stability

K. Barbara Schowen ; Departments of Chemistry and Pharmaceutical Chemistry Higuchi Biosciences Center, University of Kansas, Lawrence, Kansas 66045-0046, USA
Richard L. Schowen ; Departments of Chemistry and Pharmaceutical Chemistry Higuchi Biosciences Center, University of Kansas, Lawrence, Kansas 66045-0046, USA

Puni tekst: engleski, pdf (12 MB) str. 1491-1500 preuzimanja: 187* citiraj
APA 6th Edition
Schowen, K.B. i Schowen, R.L. (1996). Transition-state Acidities and the pH Dependence of Drug Stability. Croatica Chemica Acta, 69 (4), 1491-1500. Preuzeto s https://hrcak.srce.hr/135985
MLA 8th Edition
Schowen, K. Barbara i Richard L. Schowen. "Transition-state Acidities and the pH Dependence of Drug Stability." Croatica Chemica Acta, vol. 69, br. 4, 1996, str. 1491-1500. https://hrcak.srce.hr/135985. Citirano 02.03.2021.
Chicago 17th Edition
Schowen, K. Barbara i Richard L. Schowen. "Transition-state Acidities and the pH Dependence of Drug Stability." Croatica Chemica Acta 69, br. 4 (1996): 1491-1500. https://hrcak.srce.hr/135985
Harvard
Schowen, K.B., i Schowen, R.L. (1996). 'Transition-state Acidities and the pH Dependence of Drug Stability', Croatica Chemica Acta, 69(4), str. 1491-1500. Preuzeto s: https://hrcak.srce.hr/135985 (Datum pristupa: 02.03.2021.)
Vancouver
Schowen KB, Schowen RL. Transition-state Acidities and the pH Dependence of Drug Stability. Croatica Chemica Acta [Internet]. 1996 [pristupljeno 02.03.2021.];69(4):1491-1500. Dostupno na: https://hrcak.srce.hr/135985
IEEE
K.B. Schowen i R.L. Schowen, "Transition-state Acidities and the pH Dependence of Drug Stability", Croatica Chemica Acta, vol.69, br. 4, str. 1491-1500, 1996. [Online]. Dostupno na: https://hrcak.srce.hr/135985. [Citirano: 02.03.2021.]

Sažetak
The pH dependence of hydrolytic reactions of drugs allows some control of their stability through adjustment of the pH of storage. The transition-state acidity concept of J. L. Kurz is shown to apply to the systematics of relevant pH rate profiles. As limiting cases for the hydrolysis of a series of carboxylic acid derivatives (often employed in pro-drug modifications) in neutral and basic solution, two situations are considered: 1) larger structural effects in basic solution, in which case the most stable compound of the series has the highest transition-state pKa, and 2) larger structural effects in neutral solution, in which case the most stable compound will have the lowest transition-state pKa. The former is the expected situation for variations of reactant electronic features because the negatively charged transition state for the hydroxide-promoted reaction in basic solution should respond more sensitively to electronic effects than should the dipolar transition state for the »un- catalyzed« reaction in neutral solution. Available data for some important substrates in fact do not show the expected behavior, which may be indicative of a concerted reaction (no tetrahedral intermediate) for reactive substrates with hydroxide ion, a mechanism for which others have already provided evidence, and possible reaction through an ion pair for the reaction of reactive substrates with water. 

Hrčak ID: 135985

URI
https://hrcak.srce.hr/135985

Posjeta: 283 *