The PM6-FGC Method: Improved Corrections for Amines and Amides

Abstract

Recently, we reported a new approach to develop pairwise analytical corrections to improve the description of noncovalent interactions, by approximate methods of electronic structures, such as semiempirical quantum mechanical (SQM) methods. In particular, and as a proof of concept, we used the PM6 Hamiltonian and we named the method PM6-FGC, where the FGC acronym, corresponding to Functional Group Corrections, emphasizes the idea that the corrections work for specific functional groups rather than for individual atom pairs. The analytical corrections were derived from fits to B3LYP-D3/def2-TZVP (reference). PM6 interaction energy differences, evaluated for a reduced set of small bimolecular complexes, were chosen as representatives of saturated hydrocarbons, carboxylic, amine and, tentatively, amide functional groups. For the validation, the method was applied to several complexes of well-known databases, as well as to complexes of diglycine and dialanine, assuming the transferability of amine group corrections to amide groups. The PM6-FGC method showed great potential but revealed significant inaccuracies for the description of some interactions involving the –NH2 group in amines and amides, caused by the inadequate selection of the model compound used to represent these functional groups (an NH3 molecule). In this work, methylamine and acetamide are used as representatives of amine and amide groups, respectively. This new selection leads to significant improvements in the calculation of noncovalent interactions in the validation set.