Once the molecular mechanics program has calculated a total steric energy, as described on the earlier page, this quantity must be converted into more familiar numbers: an enthalpy of formation and a strain energy. This conversion involves the use of two sets of empirical group increments.
Enthalpies of formation (DHf) can be calculated from a set of group increments derived from heats of combustion: so many kcal/mol for each CH2, so many for each benzene ring, and so on. Molecular mechanics uses a variation of this idea, as diagrammed below:
- To the calculated steric energy are added a set of "force field increments".
- These are variables, chosen to fit the observed enthalpy of formation for a group of about 60 standard molecules.
- They have no physical significance other than their ability to give a good fit for the model set of molecules.
- The result of adding these increments, as shown, is the enthalpy of formation that is displayed by the program.
- A "strain free" enthalpy of formation is computed from group increments derived from heats of combustion.
- These increments are corrected to allow for the presence of high-energy conformers.
- Thus, for example, a calculated enthalpy of formation for butane must recognize that about 15% of the molecules exist in the gauche conformation.
- Finally, as shown, the difference between the two enthalpies of formation is the strain energy.
Exactly what the strain energy is cannot be simply defined.
- The conventional definition is that it represents the difference in energy between the actual molecule and a completely strain-free molecule of the same constitution.
- The strain-free model is a hypothetical construct.
How can we compare the energies of several molecules as computed by a molecular mechanics program?
- If the molecules are isomers, enthalpies of formation are the preferred means of comparison, and one can say, "Molecule A is more stable than molecule B."
- If the structures are not isomeric, then comparison must be based on the calculated strain energies, and one can say only, "Molecule A is less strained than molecule B".
- No statement about overall relative stabilities can be made.