Chemical bonding resonance stabilization energy

As indicated above, the barrier to prolyl cis—trans isomerization is the resonance stabilization energy that is possessed by the C-N imide bond. The task of a prolyl isomerase is, therefore, to develop an enzymatic-chemical strategy that will result in the lowering of this barrier. When one reflects on the strategies that might be used by an enzyme, one realizes that there are two general mechanisms catalysis by distortion and nucleophilic catalysis (see Scheme V). 

The reactant R2 can also be considered to be a solvent molecule. The global kinetics become pseudo first order in Rl. For a SNl mechanism, the bond breaking in R1 can be solvent assisted in the sense that the ionic fluctuation state is stabilized by solvent polarization effects and the probability of having an interconversion via heterolytic decomposition is facilitated by the solvent. This is actually found when external and/or reaction field effects are introduced in the quantum chemical calculation of the energy of such species [2]. The kinetics, however, may depend on the process moving the system from the contact ionic-pair to a solvent-separated ionic pair, but the interconversion step takes place inside the contact ion-pair following the quantum mechanical mechanism described in section 4.1. Solvation then should ensure quantum resonance conditions. 

The chemical nature of the rubber determines which bonds are the weakest and are therefore more likely to be ruptured during mastication by the statistical concentration of mechanical energy about such bonds. An increase in the degree of asymmetry, an increase in the stiffness and the packing density of macromolecules facilitate mechanical scission resonance stability will influence the... 

The energy barrier to isomerization is lowered when substrates are transferred either to acidic or organic solutions. In acidic solution, rate acceleration occurs because an alternate, low-energy pathway is provided by protonation to produce a substrate in which the C-O bond is more ketonelike and the C-N bond more aminelike, thereby destroying resonance stabilization. In organic solutions, rate acceleration occurs as a result of transferring the substrate from a nonpolar transition state to a hydrophobic environment. We will see below that enzymatic strategies for catalysis may exploit both of these chemical mechanisms. 

The available data support a mechanism involving catalysis by distortion in which the enzyme binds and stabilizes a transition state that is characterized by partial rotation about the C-N amide bond. The energy that is required to distort this bond out of planarity with the C=0 bond, thereby destroying the resonance stabilization of the amide linkage, is supplied by favorable transition state binding interactions between enzyme and substrate. As Lumry states (1986), mechanical distortion as a source of small-molecule reactivity is attractive as a basis for enzymatic catalysis. It is quite realistic to assume that a distorted substrate will have enhanced reactivity, either because its ground state or the activated complex for its chemical reaction or both are altered by strain and stress in the protein conformation. However, as mentioned previously, this distortion need not be the result of mechanical deformation but could also be the result of desolvation or electrostatic destabilization. In fact, the current data support contributions from all three mechanisms for distortion. 

The relation between the amount of resonance stabilization and the energy difierenee of the resonating states is given, for example, by L. Pauling, The Nature of the Chemical Bond, p. 18. Cornell University Press, Ithaca, N. Y. 1940. 

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