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 (MH₂·H·A)+ aggregates (A= dC, ara-C) were found to be mostly offset by isotope effect in (SX₂·H·A)+ (X=H, D) differently from the results obtained on the analogues (A= C, G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the (MH₂·H·A)+ (A= C and G) complexes vs. the (MH₂·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 [MHn·H·A]+ (n=1,2; A= dC and ara-C) complexes is reversible, while that by [MHn·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.

Enantioselective Supramolecular carriers for Nucleoside Drugs. A Thermodynamic and Kinetic Gas Phase Investigation.

ROSELLI, Graziella;
2012-01-01

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 (MH₂·H·A)+ aggregates (A= dC, ara-C) were found to be mostly offset by isotope effect in (SX₂·H·A)+ (X=H, D) differently from the results obtained on the analogues (A= C, G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the (MH₂·H·A)+ (A= C and G) complexes vs. the (MH₂·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 [MHn·H·A]+ (n=1,2; A= dC and ara-C) complexes is reversible, while that by [MHn·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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/239358
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