On the conformational varieties of adrenaline: the free molecule and the molecule in the crystal

Abstract

Refined quantum-mechanical computations invariably predict that the preferred conformers of free androgenic phenethylamines or hallucinogenic indolalkylamines should correspond to values of the torsion angles rt---+ 90 ° and rz close to + 60 or 180 °. X-ray crystallographic studies indicate that most such compounds exist in these conformations (in particular with rl ~ 90, r2-~ 180 °) in the crystals. In some cases, however, the crystalline conformer corresponds to rl -~ 0, r2-~ 180 °, an arrangement which does not even correspond to a local energy minimum on the conformational energy map for the free molecule. Such is, for example, the case for adrenaline in adrenaline hydrogen tartrate. Computations carried out for the lattice energy of this crystal and of the hypothetical crystals constructed with the usual conformers, by a procedure which uses intermolecular potential functions, show that the lattice energy of the 'experimental' crystal largely compensates for the loss in conformational energy of the constituent unit and represents a more stable arrangement than those obtained with conformers associated with rl-+ 90 °.

On the conformational varieties of 5-methoxy-N,N-dimethyltryptamine and serotonin in crystalline environment

“…In a recent paper (Caillet, Claverie & Pullman, 1976), we have inaugurated a study of the crystal structure of pharmacological compounds composed of a conjugated heterocyclic ring with an attached ethylamine side chain. Our aim was to explain the occurrence in the crystal of conformers different from those predicted as the preferred ones for the free molecule.…”

“…In the previous paper (Caillet, Claverie & Pullman, 1976) we have studied the molecule of adrenaline, which exists in the crystalline state as a planar-trans conformer with T1 = -3 ° and T2 = 179 :~, while the most stable conformation predicted for the free compound corresponds to T1 =9ff ~ and T2=60 °, i.e. a perpendicular-gauche conformation.…”

(R,R)-Labetalol hydrochloride: determination of the absolute configuration of the high-melting polymorph, C19H25N2O3+.Cl−

“…There is considerable speculation as to the lowest energy conformation of phenylethanolamine derivatives. The calculated global energy minimum (r, 90 °, r 2 -60 °) (Caillet, Claverie & Pullman, 1976) has not been seen in the solid state. In the crystalline state one conformation is almost always found (r, 90 °, r 2 180 ° 'perpendicular-trans').…”

Biological response as a function of conformation, chirality, and electronic characteristics: A catecholamine study

“…In addition, considering the small number of theoretical studies on coplanarity of catecholamines [15], a detailed conformational analysis of the free molecules may be of considerable interest. All quantum chemical calculations presented within this work were performed for the quaternary catechol-ammonium ions because of the dominant role of the cationicfraction in the chemical equilibria in the range of physiological pH [16].…”