Empirical force-field calculations limitations

In spite of its limitations, molecular mechanics (MM) is a technique that is widely used for the computation of molecular structures and relative stabilities. The advantage of MM over quantum mechanical methods is mainly based on the computational simplicity of empirical force field calculations, leading to a comparatively small computational effort for MM calculations. Therefore, even large... 

The quantitative prediction of the stereochemistry of a chemical reaction by strain energies requires 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 so far 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. The application of empirical force field calculations to the design of asymmetric transformations clearly is a worthy task, and some examples of studies in this area have been discussed above. On the basis of two examples we will now discuss some general aspects highlighting the limitations of the qualitative considerations emerging horn molecular mechanics calculations for the interpretation and support of assumed reaction pathways. 

The application of empirical force field calculations to the design of asymmetric transformations is a worthy task, and some examples of studies in this area have been discussed above. On the basis of two examples we will now discuss some general aspects highlighting the limitations of qualitative considerations emerging from molecular mechanics calculations for the interpretation and support of assumed reaction pathways. 

The limitations of the chosen approaches should be kept in mind when considering the results of these conformational calculations. Cooperative effects that might result fi om the sigma conjugation are not considered in the empirical force-field calculations, and assumptions concerning the va-... 

The resulting values for AH (= Ha u - Hgauche) are -0.9 0.2 and -1.2 0.2 klmoF for the Hs and the Ds-isotopomer, respectively. The values agree satisfactorily within the estimated error limits of 0.2 kJmol , the anti conformation being more stable than the gauche conformation. From empirical force field calculations, a AH value of -5.15 kimol (-1.23 kcalmol [3]) was deduced, which is significantly larger than the value obtained by Raman spectroscopy. 

Tliroughout this chapter and in Table 1 the inclusion of QM results as target data is evident, with the use of such data in the optimization of empirical forces fields leading to many improvements. Use of QM data alone, however, is insufficient for the optimization of parameters for condensed phase simulations. This is due to limitations in the ability to perform QM calculations at an adequate level combined with limitations in empirical force fields. As discussed above, QM data are insufficient for the treatment of dispersion... 

In this section we will discuss in some detail the relationship between molecular mechanics force field parameters and real physical parameters. As mentioned before, the fundamental difference between spectroscopic and molecular mechanics force fields is that the former are molecule-specific while the latter are general. Empirical force field parameters can be used for the calculation of unknown structures and their strain energies, and for the prediction of vibrational frequencies of new compounds. However, the parameters themselves generally have limited meaning. 

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