Ab initio assessment of the electronic structure of 5α-reduced progestins

• Published in: International journal of quantum chemistry Vol. 67; no. 5; pp. 329 - 338
• Main Author: Kubli-Garfias, Carlos
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 1998
• Subjects: 5α-progestins; ab initio calculations; allopregnanedione; allopregnanolone; electronic structure; progesterone; tetrahydroprogesterone
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/(SICI)1097-461X(1998)67:5<329::AID-QUA6>3.0.CO;2-X

Progesterone (P) yields to 5α‐reduced progestins, namely 5α‐pregnanedione (DHP), tetrahydroprogesterone (THP), and allopregnanolone (ALLO‐P). The geometries and electronic structure of these steroids were assessed by ab initio calculations using the 6‐31G* basis set. The parameters measured were bond distances, valence angles, and dihedral angles. Likewise, the following were calculated: total energy; frontier orbitals, i.e., highest occupied molecular orbital (HOMO); lowest unoccupied molecular orbital (LUMO); dipole moment; atomic charges; and electrostatic potentials. The frontier orbitals of P were located at the π‐double bond. However, the HOMO of the 5α‐progestins was extended into the molecule, while the LUMO was confined at the C20 carbonyl group. The atomic charges, electronic density surfaces and electrostatic potentials showed patterns according to the stereochemical arrangement of the C3 and C20 carbonyl and hydroxyl functional groups. Interestingly, P and THP showed the larger dipole moment and high electronic density at the A‐ring because the double bond and the 3α‐hydroxy group, respectively. The present results might explain to some extent the metabolism of the studied progestins. Similarly, some physicochemical properties, such as dipole moments and electrostatic potentials, seem related with important biological actions such as uterine contractility and control of gonadotropin secretion. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 67: 329–338, 1998