The sensitivity of intramolecular reactions to the orientation of the reacting atoms

Abstract

The contributions to rates of intramolecular and enzymatic reactions provided by proximity and correct orientation of two reacting groups are examined. It is shown that the rate enhancement arising from simple juxtaposition of two molecules or functional groups can be expressed as a statistical factor (some fraction of 55 M for aqueous solution) multiplied by a correction term for use when specific data on solution structure are available. The effect of relative orientation of two reacting groups on their rate of reaction is expressed in terms of a simple collision theory. The angular dependence of rate is assumed to arise solely from an angle-dependent potential-energy barrier determined by the magnitude of transition state bending force constants. Crude but reasonable calculations using assumed values for bending force constants in the transition state suggest that orientation may lead to rate accelerations of up to 10 4 for a properly oriented intramolecular or enzymatic reaction compared to its bimolecular counterpart. Although the final determination of the effect of orientation must be experimental, these calculations indicate that orientation of reacting groups may account for a substantial fraction of intramolecular and enzymatic catalysis.