Accelerations in the Lactonization of Trimethyl Lock Systems Are due to Proximity Orientation and not to Strain Effects

Rafik Karaman

doi:10.1155/2009/240253

Abstract

DFT at B3LYP/6-31G(d,p) and HF at 6-31G and AM1 semiempirical calculations of thermodynamc and kinetic parameters for the trimethyl lock system (an important enzyme model) indicate that the remarkable enhancement in the lactonizations is largely the result of a proximity orientation as opposed to the currently advanced strain effect.

Highlights

The study of enzyme mechanisms is of vast importance and has become central to both bioorganic chemistry and computational chemistry. Studies in this field by Bruice, Benkovic, Jencks, and Bender over the past 40 years have contributed largely to understanding the mode and scope by which certain enzymes achieve their catalytic activities [1]. These and studies of many others have been carried out in order to understand enzymatic catalysis which is characterized by high substrate specificity, chemoselectivity, and stereospecificity along with large rate enhancements
Among these are (1) the proximity model of Bruice [2, 3] on the intramolecular cyclization of dicarboxylic semiesters, (2) the “orbital steering” theory suggested by Koshland [4, 5], (3) the “spatiotemporal hypothesis” devised by Menger [6,7,8,9] which describes the importance of the distance between the two reactive centers in determining whether a reaction is inter- or intramolecular, and (4) the gem-trimethyl lock proposal of Cohen [10,11,12]
We describe the DFT at B3LYP/6-31G (d, p) and the restricted Hartree-Fock (RHF) at 6-31G levels, as well as AM1 semiempirical calculations results for the acid-catalyzed and uncatalyzed lactonization reactions of the trimethyl lock system

Summary

Introduction

The study of enzyme mechanisms is of vast importance and has become central to both bioorganic chemistry and computational chemistry Studies in this field by Bruice, Benkovic, Jencks, and Bender over the past 40 years have contributed largely to understanding the mode and scope by which certain enzymes achieve their catalytic activities [1]. These and studies of many others have been carried out in order to understand enzymatic catalysis which is characterized by high substrate specificity, chemoselectivity, and stereospecificity along with large rate enhancements. He attributed this large enhancement to what he called “stereopopulation control”

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Conclusion