Transition State Distortion Energy

This approach has proven to be quite useful in a number of applications two cycloaddition examples are examined here. 

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Patou, R. S. Kim, S. Ross, A. G. Danishefsky, S. J. Houk, K. N. Experimental Diels-Alder reactivities of cycloalkenones and cyclic dienes explained through transition-state distortion energies, Angew. Chem. Int. Ed. 2011,50,10366-10368. 

Abstract An energy decomposition scheme is presented to elucidate the importance of the change of protein conformation substates to the reduction of activation barrier in an enzyme-catalyzed reaction. The analysis is illustrated by the reaction of orotidine 5 -monophosphate decarboxylase (ODCase), in which the catalyzed reaction is at least 10 faster than the spontaneous reaction. Analysis reveals that the enzyme conformation is more distorted in the reactant state than in the transition state. The energy released from conformational relaxation of the protein is the main source of the rate enhancement. The proposed mechanism is consistent with results from site-directed mutagenesis where mutations remote from the reaction center affect kcat but not Kyi. 

This complexation accentuates both the energy and orbital distortion effects of the substituent and enhances both the reactivity and selectivity of the dienophile, relative to the uncomplexed compound.The effects are well modeled by 3-21G-level computations on the transition-state stmctures. ... 

A careful distinction must be drawn between transition states and intermediates. As noted in Chapter 4, an intermediate occupies a potential energy minimum along the reaction coordinate. Additional activation, whether by an intramolecular process (distortion, rearrangement, dissociation) or by a bimolecular reaction with another component, is needed to enable the intermediate to react further it may then return to the starting materials or advance to product. One can divert an intermediate from its normal course by the addition of another reagent. This substance, referred to as a trap or scavenger, can be added prior to the start of the reaction or (if the lifetime allows) once the first-formed intermediate has built up. Such experiments are the trapping experiments referred to in Chapters 4 and 5. 

Figure 14. Tunneling to the alternative state at energy can be accompanied by a distortion of the domain boundary and thus populating the ripplon states. All transitions exemplified by solid lines involve tunneling between the intrinsic states and are coupled linearly to the lattice distortion and contribute the strongest to the phonon scattering. The vertical transitions, denoted by the dashed lines, are coupled to the higher order strain (see Appendix A) and contribute only to Rayleigh-type scattering, which is much lower in strength than that due to the resonant transitions.

The important criterion thus becomes the ability of the enzyme to distort and thereby reduce barrier width, and not stabilisation of the transition state with concomitant reduction in barrier height (activation energy). We now describe theoretical approaches to enzymatic catalysis that have led to the development of dynamic barrier (width) tunneUing theories for hydrogen transfer. Indeed, enzymatic hydrogen tunnelling can be treated conceptually in a similar way to the well-established quantum theories for electron transfer in proteins. 

Fig. 14. Conformations of s,czs-cyclooctadiene-l,5 with calculated angles (inner values) and torsion angles (deg force field of ref. 19) (83). The additional calculated information given is (from top) symmetry, AV, AH (kcal mole-1 T = 298 K reference C2-symmetric distorted boat conformation). The three upper conformations correspond to potential energy minima, the two lower to onedimensional partial maxima (transition states).

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