SEMIEMPIRICAL ASSESSMENT OF CHANGES ON THE ELECTRONIC-STRUCTURE OF ANDROSTENE WITH THE ADDITION OF CARBONYL AND HYDROXYL-GROUPS

A systematic study on the impact of carbonyl and hydroxyl functional g roups on the electronic structure of the steroid, androst-4-ene (andro stene) was carried out by the semiempirical methods, AM1 and PM3. A to tal of 16 molecules from androstene were studied with mono and disubst ituted hydroxyl and carbonyl groups at C3 and C17. Results showed the lowering of total energies and enthalpies of formation with the additi on of the functional groups. HOMO was located always along of the C4-C 5 pi-bond. The LUMO occupied the same place except for two 17-keto and rostene structures which showed the LUMO at C17 and degeneracy at LUMO and LUMO + 1. Structures with 3-keto conformation were the most consp icuous showing higher dipole moment, lower energy in both HOMO and LUM O, some degeneracy with HOMO and HOMO-1 and more impact than the hydro xyl groups in the charges of neighbor carbon atoms. Interestingly, thi s conformation which conjugates O = C3-C4 = C5, belongs to the ring A conformation of testosterone, epitestosterone and androstenedione, thr ee well known androgens. It is concluded that the double bond of andro stenes at C4-C5 when conjugated with a carbonyl group at C3 enhances t he likelihood of biological activity.