Induced-fit in the gas phase: conformational effects on the enantioselectivity of chiral tetra-amide macrocycles.
The structure, stability, and reactivity of proton-bound diastereomeric [M x H x A]+ complexes between some amino acid derivatives (A) and several chiral tetra-amide macrocycles (M) have been investigated in the gas phase by ESI-FT-ICR and ESI-ITMS-CID mass spectrometry. The displacement of the A guest from the diastereomeric [M x H x A]+ complexes by reaction with the 2-aminobutane enantiomers (B) exhibits a distinct enantioselectivity with regards to the leaving amino acid A and, to a minor extent, to the amine reactant B. The emerging selectivity picture, discussed in the light of molecular mechanics calculations, provides compelling evidence that the most stable conformers of the selected chiral tetra-amide macrocycles M may acquire in the gas phase a different conformation by induced fit on complexation with some representative amino acid derivatives A. This leads to the coexistence in the gas phase of stable diastereomeric [M x H x A]+ eq-eq and ax-ax structures, in proportions depending on the configuration of A and M and characterized by different stability and reactivity toward the 2-aminobutane enantiomers. The enantioselectivity of the gas-phase A-to-B displacement in the diastereomeric [M x H x A]+ complexes essentially reflects the free energy gap between the homo- and heterochiral [M x H x A]+ complexes, except when the tetra-amidic host presents an additional macrocycle generated by a decamethylene chain. In this case, the measured enantioselectivity mostly reflects the stability difference between the relevant diastereomeric transition structures.
Gasparrini
Francesco
F
Dipartimento degli Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, 00185 Roma, Italy.
Pierini
Marco
M
Villani
Claudio
C
Filippi
Antonello
A
Speranza
Maurizio
M
D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D000613:Aminobutyrates / Q000737:chemistry; D005740:Gases / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D000613:Aminobutyrates; D005740:Gases; D047028:Macrocyclic Compounds; C012223:alpha-aminobutyric acid