BIOORGANIC CHEMISTRY 8,45-58 (1979) Solvent Isotope Effects in Intramolecular Catalysis: Acyl Transfer Reactions of 4-Nitrophenyl5-Nitrosalicylate in Aqueous Tris Buffer RICHARD D. GANDOUR, MARSHA A. PIVERT,’ ELLA L. KELLEY,~ BENNIE D. MINOR,~ RONALD SPENCER,~ RICHARD H. INGRAHAM,’ AND STEVEN J. SPINDLER’ Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 Received March lo,1978 A kinetic study of the reactions of 4nitrophenyl 5nitrosalicylate in aqueous Tris buffer at 25°C has revealed three kinetically significant reactions: Tris aminolysis of the m-ionized substrate, Tris aminolysis of the ionized substrate, and spontaneous hydrolysis of the ionized substrate. Solvent isotope effectshave been measured for all three reactions. Mechanisms are discussed, and the conclusion is reached that intra- molecular catalysis is operating in only the spontaneous hydrolysis. INTRODUCTION In the past few years there has been a growing interest in chemical models of enzyme action. An especially useful class of reactions is one in which the model catalyst and substrate are bound to the same molecular framework. The basic premise is that reacting groups juxtaposed on the same molecule serve as a valid analogy for a reaction in an enzyme-substrate complex. A number of reviews have appeared on this topic (1). In this large body of research, two distinct types of models emerge. The first type is mimetic models; i.e., the reactions model specific enzymes. This type of chemical modeling is the subject of an excellent review by Fife (2). The second type is non- mimetic models; i.e., the reactions model a specific feature of the general process of enzyme catalysis. This type is more general and covers catalysis by functional groups. A classic example of intramolecular catalysis of the nonmimetic type, the hydrolysis of 4-nitrophenyl Snitrosalicylate, was reported by Bender et al. (3). They suggested that the hydrolysis reaction from pH 7 to 10 occurred via intramolecular general base catalysis (Eq. 111). Their conclusion was arrived at by excluding the kinetically equivalent mechanism, intramolecuiar general acid-specific base catalysis (Eq. 121). -3 products 111 121 r Undergraduate research intern. * Work-Study Program participant. r Project Catalyst participant, Summer 1977. 45 0045-2068/79/010045-14$02.00/O Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Br~tam