AB-INITIO ASSESSMENT OF THE ELECTRONIC-STRUCTURE OF 5-ALPHA-REDUCED PROGESTINS

Progesterone (P) yields to 5 alpha-reduced progestins, namely 5 alpha- pregnanedione (DHP), tetrahydroprogesterone (THP), and allopregnanolon e (ALLO-P). The geometries and electronic structure of these steroids were assessed by ab initio calculations using the 6-31G'' basis set. T he parameters measured were bond distances, valence angles, and dihedr al angles. Likewise, the following were calculated: total energy; fron tier orbitals, i.e., highest occupied molecular orbital (HOMO); lowest unoccupied molecular orbital (LUMO); dipole moment; atomic charges; a nd electrostatic potentials. The frontier orbitals of P were located a t the pi-double bond. However, the HOMO of the 5 alpha-progestins was extended into the molecule, while the LUMO was confined at the C20 car bonyl group. The atomic charges, electronic density surfaces and elect rostatic potentials showed patterns according to the stereochemical ar rangement of the C3 and C20 carbonyl and hydroxyl functional groups. I nterestingly, P and THP showed the larger dipole moment and high elect ronic density at the A-ring because the double bond and the 3 alpha-hy droxy group, respectively. The present results might explain to some e xtent the metabolism of the studied progestins. Similarly, some physic ochemical properties, such as dipole moments and electrostatic potenti als, seem related with important biological actions such as uterine co ntractility and control of gonadotropin secretion. (C) 1998 John Wiley & Sons, Inc.