Quantum mechanics conformational transitions

Transition metal (TM) systems present a fundamental dilemma for computational chemists. On the one hand, TM centers are often associated with relatively complicated electronic structures which appear to demand some form of quantum mechanical (QM) approach (1). On the other hand, all forms of QM are relatively compute intensive and are impractical for conformational searching, virtual high-throughput screening, or dynamics simulations... 

RB3LYP calculations indicate that the s-cis conformer of peroxy acids is more stable than the s-trans conformer. Calculations on the reaction of prop-2-enol with some peroxy acids showed that trans-transition states collapse to the epoxide via a 1,2-shift, whereas a 1,4-shift is operable for cis-transition states.195 Quantum mechanical calculations have been performed on the migration step of the Baeyer-Villiger rearrangements of some substituted acetophenones with m-chloroperbenzoic acid (m-CPBA). The energy barriers, charge distributions and frontier molecular orbitals, determined for the aryl migration step, have been used to explain the effects of substituents on the reactivity of the ketones.196... 

The quantitative prediction of the stereochemistry of a chemical reaction by strain energies requires the knowledge of the reaction mechanism, i.e., the selective intermediates and/or transition states involved, and an accurate force field for the transient species. As discussed above, these are two demanding problems and, with a small number of exceptions involving combined quantum-mechanical/molecular-mechan-ical methods there are no reports of studies in this area that have used molecular mechanics for quantitative predictions at the same level of accuracy as for conformational analyses. Quantum-mechanical approaches are more appropriate in this area. 

One of the most important advances in molecular quantum mechanics of the last fifteen years has been the increased ease and accuracy of predicting molecular conformation through purely theoretical models [1-4]. The stable geometries of molecules as yet unmade can be determined and molecular properties of these systems studied. The conformations and properties of electronically excited molecules can be examined theoretically, whereas experimentally these geometries are often very elusive. Transition states, the species that separates reactants from products, and that have but fleeting existence — if at all, experimentally — are also obtainable using molecular quantum quantum mechanics. 

Note Added in Proofs. There has been additional work on the calculation of conformational energies for cyclohexane, see Section II. Wiberg and Boyd 129) conclude that non-bonded interactions make little contribution to the barrier, the most important component of which is torsional strain, in agreement with earlier work. Quantum mechanical calculations of various conformations which do not by their nature allow a spUtting of energies into Bayer strain, Pitzer strain, and van der Waals strain, have also been made I30,i3i), it has been concluded 12D that transition state conformations 1 and 2 are of similar energies i. e. that there is pseudorotation in the transition state as proposed by Pickett and Strauss 29,30),... 

These include multipole moments, molecular polarizabilities, ionization potentials, electron affinities, charge distributions, scattering potentials, spectroscopic transitions, geometries and energies of transition states, and the relative populations of various conformations of molecules. Some of these properties are directly related to molecular reactivity (e.g., charge distribution, molecular polarizabilities, scattering potentials), and they can be implemented in QSAR studies. Quantum mechanical methods can therefore be used to obtain reactivity characteristics in order to relate molecular structure to the observed biological activity (183, 230). 

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