Atom Types Independent Molecular Mechanics Method for Predicting the Conformational Energy of Small Molecules

We
previously implemented a well-known qualitative chemical principle
into an accurate quantitative model computing relative potential energies
of conformers. According to this principle, hyperconjugation strength
correlates with electronegativity of donors and acceptors. While this
earlier version of our model applies to σ bonds, lone pairs,
disregarded in this earlier version, also have a major impact on the
conformational preferences of molecules. Among the well-established
principles used by organic chemists to rationalize some organic chemical
behaviors are the anomeric effect, the alpha effect, basicity, and
nucleophilicity. These effects are directly related to the presence
of lone pairs. We report herein our effort to incorporate lone pairs
into our model to extend its applicability domain to any saturated
small molecules. The developed model H-TEQ 2 has been validated on
a wide variety of molecules from polyaromatic molecules to carbohydrates
and molecules with high heteroatoms/carbon ratios. Interestingly,
this method, in contrast to common force field-based methods, does
not rely on atom types and is virtually applicable to any organic
molecules.