title: Unraveling the molecular recognition of amino acid derivatives by a pseudopeptidic macrocycle: ESI-MS, NMR, fluorescence, and modeling studies.
abstract: The binding between a pseudopeptidic macrocyclic naphthalenophane and different N-protected amino acid derivatives has been thoroughly studied by ESI-MS, NMR, fluorescence, and molecular modeling. Careful NMR titration experiments led to the characterization of the intermolecular noncovalent interactions, reflecting a slight side chain and l-stereoselectivity of the host-guest complexes. The data suggest the formation of an intimate ionic pair after the proton transfer from the carboxylic substrate to the amino macrocycle. Additional intermolecular interactions like H-bonding and pi-pi contacts are also important. This receptor shows a stronger interaction with substrates bearing aromatic rings, either in the side chain or in the N-protecting group. Besides, for N-Z-Phe-OH, a moderate enantioselectivity has been observed. Mass spectrometry suggests the formation of supramolecular complexes with stoichiometries higher than 1:1. The dual nature of the fluorescence emission of the macrocyclic receptor allowed determining binding constants and pertinent thermodynamic parameters. On the basis of the experimental data (NMR titrations, intermolecular ROESY, VT-NMR) and with the help of molecular modeling, a reasonable structure for the supramolecular complexes can be proposed, in which the interactions with the naphthyl ring of the receptor play a fundamental role in the strength and selectivity of the molecular recognition event.
authors.affiliation: Departamento de Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), C/Jordi Girona 18-26, E-08034, Barcelona, Spain. ignacio.alfonso@iqac.csic.es
authors.forename: Ignacio
authors.initials: I
authors.lastname: Alfonso
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Burguete
authors.forename: Francisco
authors.initials: F
authors.lastname: Galindo
authors.forename: Santiago V
authors.initials: SV
authors.lastname: Luis
authors.forename: Laura
authors.initials: L
authors.lastname: Vigara
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D012996:Solutions; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D005740:Gases; D047028:Macrocyclic Compounds; D009281:Naphthalenes; D010455:Peptides; D012996:Solutions; C031721:naphthalene