title: Enantioselective supramolecular carriers for nucleoside drugs. A thermodynamic and kinetic gas phase investigation.
abstract: The enantioselective interactions between chiral tetra-amidic receptors and nucleosides have been investigated by the ESI-IT-MS and ESI-FT-ICR-MS methodologies. Configurational effects on the CID fragmentation of diastereomeric [M(H)(2)•H•A](+) aggregates (A = 2'-deoxycytidine dC, citarabine (ara-C) were found to be mostly offset by isotope effect in [S(X)(2)•H•A](+) (X = H, D) differently from the results obtained on the analogues (A = cytidine C and gemcitabine G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the [M(H)(2)•H•A](+) (A = C and G) complexes vs. the [M(H)(2)•H•A](+) (dC and ara-C) ones is fully confirmed by the kinetics of their uptake of the 2-aminobutane enantiomers, measured by FT-ICR mass spectrometry. Indeed, uptake of the 2-aminobutane enantiomers by [M(H)(n)•H•A](+) (n = 1,2; A = dC and ara-C) complexes is reversible, while that by [M(H)(n)•H•A](+) (n = 1,2; A = C and G) is not. The most encouraging result concerning the measured fragmentation and kinetic differences between C and ara-C, that are just epimers, indicates the possibility to subtly modulate the non-covalent drug/receptor interactions, through the electronic properties of the 2'-substituent on the nucleoside furanose ring, and furthermore on its three-dimensional position.
authors.affiliation: Chimica e Tecnologie del Farmaco, Facoltà di Farmacia, Sapienza University of Rome, Italy. caterina.fraschetti@uniroma1.it
authors.forename: Caterina
authors.initials: C
authors.lastname: Fraschetti
authors.forename: Antonello
authors.initials: A
authors.lastname: Filippi
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Crestoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Villani
authors.forename: Graziella
authors.initials: G
authors.lastname: Roselli
authors.forename: Stefano Levi
authors.initials: SL
authors.lastname: Mortera
authors.forename: Maurizio
authors.initials: M
authors.lastname: Speranza
mesh_terms: D004337:Drug Carriers; D005740:Gases / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D009705:Nucleosides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D004337:Drug Carriers; D005740:Gases; D009705:Nucleosides