Approximation, entropy and intramolecular reactions

Bringing 2 molecules together to form a transition state in a bimolecular reaction is generally accompanied by a large loss of entropy as the transition state is a more ordered system. The formation of the transition state from the independently moving and rotating reactants is accompanied by a large loss of translational and rotational entropy. 

Historically, there was a delay in appreciating the magnitude of the entropic contribution to intramolecular and enzyme-catalysed reactions because of the wide variation observed in the rate enhancements of intramolecular reactions. It is well known that intramolecular reactions (Eqn. 28) in which the reactants are covalently bonded to one another, often proceed at very much faster rates than those of the analogous intermolecular reactions (Eqn. 29). These intramolecular reactions are frequently taken as models for enzyme-catalysed reactions where the reactants are held close together in the enzyme-substrate complex (Eqn. 30).It is therefore often 

The problem, then, is to estimate the maximum rate difference between (for the enzyme-catalysed reaction) and (for the uncatalysed reaction) (Eqn. 27) 

Typical rate enhancements and favourable equilibria of intramolecular reactions are illustrated by some reactions of succinic acid and its derivatives [15], The equilibrium constant for succinic anhydride formation from succinic acid (Eqn. 31) is 3 X 10 moles/1 more favourable than that for acetic anhydride formation from acetic acid (Eqn. 32), an analogous intermolecular reaction. A similar situation exists 

The rate enhancements and favourable equilibria have units of concentration because a unimolecular reaction is being compared with a bimolecular one. For this reason the rate enhancement is sometimes called the effective concentration or effective molarity , which is the hypothetical concentration of one of the reactants in the intermolecular reaction required to make the intermolecular reaction proceed at the same rate as that of the intramolecular one [15]. 

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