Conformational barriers, additivity

In this chapter, we have carried out systematic investigations, comparing calculations carried out using the standard models of ab initio theory with experintental measurements of geometrical structures, dipole moments, atomization energies, reaction enthalpies and conformational barriers. In addition, we investigated van der Waals systems in Section 8.5. Let us now take stock of these calculations to see where the best calculations - namely, those carried out at the CCSD(T) level - stand vis-d-vis the best experiments. 

Such a structure implies that there would be a barrier to rotation about the C(2)—C(3) bond and would explain why the s-trans and s-cis conformers lead to different excited states. Another result that can be explained in terms of the two noninterconverting excited states is the dependence of the ratio of [2 + 2] and [2 + 4] addition products on sensitizer energy. The s-Z geometry is suitable for cyclohexene formation, but the s-E is not. The excitation energy for the s-Z state is slightly lower than that for the s-E. With low-energy sensitizers, therefore, the s-Z excited state is formed preferentially, and the ratio of cyclohexene to cyclobutane product increases. ... 

It is known that the penultimate unit influences the conformation of both model radicals and propagating radicals.32 3 Since addition requires a particular geometric arrangement of the reactants, there are enthalpic barriers to overcome for addition to take place and also potentially significant effects on the entropy of activation. Comparisons of the rate constants and activation parameters for homopropagation with those for addition of simple model radicals to the same monomers also provide evidence for significant penultimate unit effects (Section 4.5.4). 

A quite different and complimentary approach is to assume that addition of a nucleophile to an acyl derivative (RCOX) would follow the linear free energy relationship for addition of the nucleophile to the corresponding ketone (RCOR, or aldehyde if R=H) if conjugation between X and the carbonyl could be turned off, while leaving its polar effects unchanged. This can be done if one knows or can estimate the barrier to rotation about the CO-X bond, because the transition state for this rotation is expected to be in a conformation with X rotated by 90° relative to RCO. In this conformation X is no longer conjugated, so one can treat it as a pure polar substituent. Various values determined by this approach are included in the tables in this chapter. 

There has been considerable recent activity developing appropriate parameters to allow semi-empirical methods to describe a variety of biologically important systems, and their related properties, such as (i) enzyme reactivity, including both over- and through-barrier processes, (ii) conformations of flexible molecules such as carbohydrates, (iii) reactivity of metalloenzymes and (iv) the prediction of non-covalent interactions by addition of an empirical dispersive correction. In this review, we first outline our developing parameterisation strategy and then discuss progress that has been made in the areas outlined above. 

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