Premium
Comparative AM1 study of the electronic structure of etiocholanes
Author(s) -
KubliGarfias Carlos,
Vazquez Ricardo,
Mendieta Jesús
Publication year - 1997
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1997)64:2<249::aid-qua13>3.0.co;2-4
Subject(s) - chemistry , androsterone , homo/lumo , molecular orbital , carbonyl group , crystallography , relaxation (psychology) , computational chemistry , mndo , stereochemistry , steroid , organic chemistry , molecule , hormone , psychology , social psychology , biochemistry
Etiocholanes are metabolites of androstenedione(4‐androsten‐3,17‐dione) and testosterone(17β‐hydroxy‐4‐androsten‐3‐one). These compounds are produced by theaction of 5‐reductases which break the π double bond of the androstenesat C 4 and C 5 . The most important etiocholanes are5β‐androstanedione (etiocholanedione),3α‐hydroxy‐5β‐androstan‐17‐one (etiocholanolone),3β‐hydroxy‐5β‐androstan‐17‐one (epietiocholanolone), and17β‐hydroxy‐5β‐androstan‐3‐one (5β‐dihydrotestosterone;5βDHT). Among their most important biological effects are depressionof the central nervous system, relaxation of smooth muscle, and stimulationof sexual behavior. The intent of the present study is a determination ofthe effects of carbonyl and hydroxyl groups at C 3 andC 17 on the electronic structure of these androgens, in anattempt to gain some insight into their biological action. All calculationswere of the semiempirical AM1 type. The decrease of enthalpy caused by anhydroxyl group was found to be twice that of a carbonyl group. The effectof two groups was found to be additive. Carbonyl groups on the other handled to an increase of dipole moment and of the electrostatic charges onneighboring carbons that were higher than those produced by hydroxylgroups. Carbonyl groups at C 17 pushed the highest occupiedmolecular orbital (HOMO) to higher energy whereas a carbonyl atC 3 had little or no effect. However, in mono and di‐ketostructures, both HOMO and lowest unoccupied molecular orbital (LUMO) werelocated as expected closer to the carbonyl group. Etiocholanedione, adiketo structure, showed degeneracy of frontier orbitals with its relatedHOMO−1 and LUMO+1. Structures with mono‐hydroxyl or di‐hydroxylfunctional groups showed the lowest HOMO values; the highest LUMO valuesand quasi degeneracy of HOMO−1 and LUMO+1. The HOMO and LUMO ofetiocholane and for the mono and di‐hydroxyl structures were observeddiffused throughout the molecules in a “sausagelike” or“ribbonlike” fashion. These results might explain somemetabolic steps. Likewise, the difference of intermolecular forces, i.e.,dipole moments and charges displayed by the carbonyl and hydroxyl groups,might help to elucidate some biological effects. © 1997 JohnWiley & Sons, Inc. Int J Quant Chem 64 : 249–254, 1997