In considering the rate enhancement accompanying the conversion of a bimolecular reaction into an intramolecular or intracomplex (enzymic) reaction several factors must be considered. In the first place, when a functional group, S, is held via covalent bonds in proximity to a second reactant group, U, or when a substrate, S, is bound to an enzyme to provide a productive E-S complex, the ordering of reaction centers results in a loss of translational and rotational degrees of freedom in the ground state. This gives rise to an increase in ΔS‡, resulting in an increased rate of reaction. Second, when S and U are found within a single molecule or when S enjoys freedom of movement within the E-S complex, the positional orientation of the reactive centers is of importance in determining the decrease in ΔF‡ brought about by bringing these centers together. The third consideration is that if the reactive...