Modelling amphetamine/receptor interactions: a gas-phase study of complexes formed between amphetamine and Some chiral amido[4]resorcinarenes.
Diastereomeric proton-bound complexes formed between (R)- and (S)-amphetamine and some chiral amido[4]resorcinarene receptors display significant enantioselectivities when reacting with the enantiomers of 2-aminobutane in the gas phase. The origins of the measured enantioselectivities are discussed in the light of molecular mechanics calculations and molecular dynamics simulations and are ascribed to a combination of structural and dynamic factors, including the lengths and the isomeric structures of the host asymmetric pendants and the frequencies and amplitudes of their motion, as well as those of the proton-bonded amphetamine guests. The emerging picture may represent a starting point for deeper comprehension of the factors determining the different affinities of (R)- and (S)-amphetamine towards various chiral receptors, their selective binding to the monoamine transporters, and their sensitivity to specific inorganic ions.
Botta
Bruno
B
Dipartimento degli Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, 00185 Roma, Italy.
Tafi
Andrea
A
Caporuscio
Fabiana
F
Botta
Maurizio
M
Nevola
Laura
L
D'Acquarica
Ilaria
I
Fraschetti
Caterina
C
Speranza
Maurizio
M
D000661:Amphetamine / Q000737:chemistry*; D047250:Calixarenes / Q000737:chemistry*; D003198:Computer Simulation; D005740:Gases / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D009010:Monte Carlo Method; D011941:Receptors, Adrenergic / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013237:Stereoisomerism
D005740:Gases; D011941:Receptors, Adrenergic; C036062:amphetamine receptor; D047250:Calixarenes; D000661:Amphetamine