Interactions of vinca alkaloid subunits with chiral amido[4]resorcinarenes: a dynamic, kinetic, and spectroscopic study.
The stereoselectivity of the reaction between (R)-(-)-2-butylamine and the diastereomeric proton-bound complexes of (+)-catharanthine (C) or (-)-vindoline (V) with some chiral amido[4]resorcinarenes has been investigated in the gas phase by ESI-FT-ICR-MS. The reaction stereoselectivity (0.56 < k(homo)/k(hetero) < 16.9) is found to depend critically on the functional groups present in the chiral pendants of the hosts. Rationalisation of the kinetic results is based on careful computational and spectroscopic studies of the most stable conformations of (+)-catharanthine and its protonated form in the isolated state and in water, as well as in a representative host structure. The emerging picture points to the relevant diastereomeric proton-bound complexes as quasi-degenerate, thus suggesting that their stereoselectivity in the guest exchange reaction is mostly due to kinetic factors. The results of this study may represent a starting point for a deeper comprehension of the intrinsic factors that endow these molecules, and their dimeric forms, with their biochemical properties.
Botta
Bruno
B
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza-Università di Roma, P.le A. Moro, 5-00185 Roma, Italy. maurizio.speranza@uniroma1.it
Fraschetti
Caterina
C
Novara
Francesca R
FR
Tafi
Andrea
A
Sacco
Fabiola
F
Mannina
Luisa
L
Sobolev
Anatoli P
AP
Mattay
Jochen
J
Letzel
Matthias C
MC
Speranza
Maurizio
M
D000588:Amines / Q000737:chemistry*; D047250:Calixarenes / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D006838:Hydrocarbons / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D014748:Vinca Alkaloids / Q000737:chemistry*
D000588:Amines; D006838:Hydrocarbons; D014748:Vinca Alkaloids; C466160:resorcinarene; D047250:Calixarenes; D010649:Phenylalanine; D002244:Carbon