Ae. Howard et al., A MOLECULAR MECHANICAL MODEL THAT REPRODUCES THE RELATIVE ENERGIES FOR CHAIR AND TWIST-BOAT CONFORMATIONS OF 1,3-DIOXANES, Journal of computational chemistry, 16(2), 1995, pp. 243-261
We present molecular mechanics calculations on the conformational ener
gies of several 2,2-dimethyl-trans-4,6-disubstituted-1,3-dioxanes. Pre
vious studies by Rychnovsky et al. have suggested that the relative co
nformational energies of chair and twist-boat forms of these 1,3-dioxa
nes were poorly represented by the molecular mechanical models MM2 an
d MM3 (MacroModel implementations of MM2 and MM3) both when compared
to experiment and to high-level quantum mechanical calculations. We ha
ve studied these molecules with a molecular mechanical force field whi
ch features electrostatic-potential-based atomic charges. This model d
oes an excellent job of reproducing the relative conformational energi
es of the highest level of theory (MP2/6-31G) applied to the problem.
Furthermore, when empirically corrected using the MP2/6-31G relative
conformational energies of the unsubstituted compound 2,2,4-trimethyl
-1,3-dioxane, the absolute energy differences calculated with this new
model between the chair and twist-boat conformers for five substitute
d compounds are within an average of 0.30 kcal/mol of the MP2/6-31G v
alues. The correlation with experiment is also very good. One can, how
ever, modify the initial molecular mechanical model with a single V-1(
-O-C-O-C-) torsional potential and do an excellent job in reproducing
the absolute conformational energies of the dioxanes as well, with an
average error in conformational energies of 0.45 kcal/mol. This same t
orsional potential was independently developed by comparing ab initio
and molecular mechanical energies of the molecule 1,1-dimethoxymethane
. Thus, we have succeeded in developing a general molecular mechanical
model for 1,3-dioxoalkanes. In addition, we have compared the standar
d MM2 and MM3 models with MM2 and MM3* (ref. 2) and have found some s
ignificant differences in relative conformational energies between MM2
and MM2. MM2 has an improved correlation with the best ab initio dat
a compared to MM2 but is still significantly worse than that found wi
th lower-level ab initio or AM1 semiempirical quantum mechanics or the
new molecular mechanical model presented here. MM3 leads to conformat
ional energies very similar to MM3. Energy component analysis suggest
s that the single most important element in reproducing the conformati
onal equilibrium is the electrostatic energy. This fact rationalizes t
he success of AMBER models, whose fundamental tenet is the accurate re
presentation of quantum mechanically calculated molecular electrostati
c effects. (C) 1995 by John Wiley and Sons, Inc.