Molecular characteristics of biogenic monoamines and their analogs

Abstract

Until recently there has been very limited information concerning the molecular geometry and conformation of biogenic monoamines and this lack of knowledge has seriously hampered efforts to unravel the structure—function relationships at the molecular level. Nevertheless, several theories have been proposed regarding interaction between the monoamines and their receptor sites. This is especially true for the neurohumoral transmitters dopamine, noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine), the target areas of which seem to be specific not only in the sense of chemical structure but also from the steric point of view. The well-known differences in biological activity due to chiralty illustrate the importance of the three-dimensional architecture of the molecules and indicate also the presence of stereospecific receptor sites. A detailed knowledge of the conformation of the biogenic monoamines would not only elucidate the requirements upon a natural or synthetic monoamine for proper function but also give indirect information about the geometry of the receptor sites.

Ab initioMO investigation of the ethanolamine–formic acid complex

“…of the HCOO-ion as obtained from literature [ 18,191. The ethanolamine molecular coordinates were obtained from x-ray studies of noradrenaline [20], the hydrogen to the nitrogen atom. The supermolecular approach was used to model the solvent perturbation of the complex by attaching two water molecules to the carboxylic oxygen atoms [8,9,23,24].…”

α‐adrenoceptors: Recent developments

“…164 These authors propose, based on a review of a large volume of literature dealing with conformations of biogenic amines, that potent, directly acting phenethylamines should have the five following characteristics: (i) a six-membered aromatic ring system, (ii) an extended ethylamine side chain oriented approximately perpendicular to the aromatic ring system, (iii) a positively charged nitrogen atom (at physiological pH) on the ethylamine side chain, (iv) a hydrophilic and hydrophobic side of the molecule resulting from the P-hydroxyl group being oriented on the same side of the molecule [cis] as the mefa phenolic hydroxyl group of the aromatic ring, and (v) an R absolute configuration at the P-carbon atom to which is attached a hydroxyl group. According to Carlstrom ef ~l .…”

p-Hydroxyephedrinium dihydrogenphosphate

“…The distance D N of the amino N atom from the centre of the phenyl ring is 5.128 (5) ,~ and the height of this N atom from the phenyl ring plane is 1.301 (4) ,~. It has been found in other biologicall), active amines that the D N distance is around 5 A (Hebert, 1979;Post & Kennard, 1974;Giesecke, 1973); this appears to be a preferred conformation necessary for activity at the receptor site (Carlstr6m, Bergin & Falkenberg, 1973). Such conformational features are also observed for phenylethylamines in interactive situations (Dattagupta, Meyer & Mukhopadhyay, 1982;Mukhopadhyay, Dattagupta & Simonetta, 1989;Hearn, Freeman & Bugg, 1973;Hebert, 1978) in a similar manner to other monohydrogenphosphates and dihydrogenphosphates.…”