Conformational preferences of neurotransmitters: Norephedrine and the adrenaline analogue, 2-methylamino-1-phenylethanol

The conformational preferences of the neurotransmitters (1R2S) norephedrine and 2-methylamino-1-phenylethanol (MAPE) have been examined under free-jet expansion conditions using a combination of laser-induced fluorescence (LIF), mass-selected resonant 2-photon ionization (R2PI), and infrared ion-dip spectroscopy together with ab initio calculations. Comparison of experimental infrared spectra and rotational band contours with ab initio data has allowed a full structural assignment of three conformers in MAPE and two in norephedrine. All five conformers are stabilized by intramolecular hydrogen bonding between the functional groups of the ethanolamine side chain, with the OH group acting as a proton donor. Further stabilizing interactions are provided by NH . . . pi hydrogen bonds and by dispersive interactions between the methyl group of the side chain and the aromatic ring. A delicate balance of these factors controls both the relative stabilities of the conformers and, through cooperative effects, the strength of the primary OH . . .N hydrogen bond. The existence of a unique IR absorption spectrum for each individual conformer provides a powerful tool for the assignment of molecular conformation.