A brief overview of the performance of molecular mechanics and quantum chemical models (including semi-empirical models, Hartree-Fock models, density functional models and LMP2 and MP2 models) with regard to the calculation of equilibrium and transition-state geometries, conformations and reaction thermochemistry is provided below. This is based on an extensive series or comparisons presented in A Guide to Molecular Mechanics and Quantum Chemical Comparisons which accompanies Spartan'06. For each task the methods are "graded" as follows
G | good |
C | good with cautious application |
P | poor |
task | molecular mechanics |
semi- empirical |
Hartree- Fock |
density functional |
LMP2 | MP2 |
---|---|---|---|---|---|---|
geometry(organic) | C | G | G | G | - | G |
geometry(metals) | - | G | P | G | - | P |
transition-state geometry | - | C | G | G | - | G |
conformation | G | P | G | G | - | G |
thermochemistry (general) | - | P | C | G | G | G |
thermochemistry (isodesmic) | - | P | G | C | G | G |
cost | low ------------------------------> high |
Hartree-Fock models with basis sets larger than 6-31G* do not provide significantly improved descriptions of either equilibrium or transition-state geometries over the Hartree-Fock 6-31G* model and, in most cases, the 3-21G model. Note, however, that MP2 and density functional models require (at the very least) basis sets which incorporate polarization functions.
Hartree-Fock models do not provide a reliable account of the geometries of compounds incorporating transition metals, but the PM3 semi-empirical model and density functional models provide good accounts. MP2 models provide good geometries for some transition metal systems, but very poor geometries for others.
Semi-empirical models may in some cases be suitable for identifying conformational minima, and for determining the geometries of these minima, but they are not suitable at providing accurate relative conformer energies.
The MMFF molecular mechanics model provides an excellent account of conformational energy differences in organic compounds. Note, however, that most of the data used in the assessment were also used to parameterize MMFF. Caution is needed in the application of MMFF outside the original range of its parameterization.
LMP2, MP2 and density functional models are needed to accurately account for the energetics of reactions where bonds are broken or formed and to properly describe absolute activation energies. Hartree-Fock and local density models are unsatisfactory. Hartree-Fock models are satisfactory in description of relative activation energies.
Hartree-Fock, LMP2 and MP2 models provide an excellent account of the energetics of isodesmic reactions. Density functional models are not reliable in all instances and should be applied only with caution.
Semi-empirical models are unsatisfactory in their description of the energetics of all types of reactions, isodesmic processes included.
Molecular mechanics models are restricted to the description of molecular equilibrium geometry and conformation. They are perhaps the only practical techniques for searching conformation space for any but the simplest molecules or for systems with more than a few degrees of conformational freedom.
Semi-empirical models are particularly attractive for:LMP2, MP2 and density functional models are needed for accurate descriptions of the thermochemistry of reactions which involve explicit bond making or breaking, and for calculation of absolute activation energies. Local density models do not provide acceptable results, but the other density functional models provide good descriptions of reactions which involve net bond making or breaking. In practice, LMP2 and MP2 models may only be applied to relatively small molecules, whereas density functional models are comparable in cost to Hartree-Fock models for molecules of moderate size and less costly for large molecules.
Density functional models are particularly attractive for: