Conformational preferences of neurotransmitters: Ephedrine and its diastereoisomer, pseudoephedrine

The conformational preferences of the diastereomeric neurotransmitters (1R2 S) ephedrine and (1S2S) pseudoephedrine have been studied in the gas phase, under free jet-expansion conditions, using ultraviolet spectroscopy (both R2PI and LIF) and infrared ion-dip and hole-burning spectroscopy in combina tion with ab initio calculation. This has led to the identification and ass ignment of two conformers in ephedrine and four in pseudoephedrine. Assignm ents have been made by comparing their experimental infrared and LIF spectr a with ab initio vibrational frequencies and ultraviolet rotational band co ntours. The relative stabilities of the conformers are controlled by a deli cate balance between intramolecular hydrogen bonding and dispersive interac tions between the methyl groups of the side chain, both with each other and with the aromatic ring. The relative conformational stabilities calculated for ephedrine do not agree with the experimental results; two of its low-l ying conformers were detected, but a third, lying at an intermediate energy , was not. The possibility of its collisional relaxation into the global mi nimum during the supersonic expansion was not supported by the ab initio ca lculations, which predict a substantial barrier along the minimum energy pa thway. It is possible that the combination of a relatively weak transition moment and a lack of facile pathways for relaxation from higher lying struc tures into the "missing" conformer may play a role.