Semiempirical assessment of changes on the electronic structure of androstene with the addition of carbonyl and hydroxyl groups

Abstract

A systematic study on the impact of carbonyl and hydroxyl functional groups on the electronic structure of the steroid, androst-4-ene (androstene) was carried out by the semiempirical methods, AM1 and PM3. A total of 16 molecules from androstene were studied with mono and disubstituted hydroxyl and carbonyl groups at C3 and C17. Results showed the lowering of total energies and enthalpies of formation with the addition of the functional groups. HOMO was located always along of the C4C5 π-bond. The LUMO occupied the same place except for two 17-keto androstene structures which showed the LUMO at C17 and degeneracy at LUMO and LUMO + 1. Structures with 3-keto conformation were the most conspicuous showing higher dipole moment, lower energy in both HOMO and LUMO, some degeneracy with HOMO and HOMO-1 and more impact than the hydroxyl groups in the charges of neighbor carbon atoms. Interestingly, this conformation which conjugates O  C3C4  C5, belongs to the ring A conformation of testosterone, epitestosterone and androstenedione, three well known androgens. It is concluded that the double bond of androstenes at C4C5 when conjugated with a carbonyl group at C3 enhances the likelihood of biological activity.