title: Pyrrolic tripodal receptors effectively recognizing monosaccharides. Affinity assessment through a generalized binding descriptor.
abstract: Pyrrolic and imino (3) or amino (4) H-bonding ligands were incorporated into a benzene-based tripodal scaffold to develop a new generation of receptors for molecular recognition of carbohydrates. Receptors 3 and 4 effectively bound a set of octylglycosides of biologically relevant monosaccharides, including glucose (Glc), galactose (Gal), mannose (Man), and N-acetyl-glucosamine (GlcNAc), showing micromolar affinities in CDCl3 and millimolar affinities in CD3CN by NMR titrations. Both receptors selectively recognized Glc among the investigated monosaccharides, with 3 generally less effective than 4 but showing selectivities for the all-equatorial beta-glycosides of Glc and GlcNAc among the largest reported for H-bonding synthetic receptors. Selectivities in CDCl3 spanned a range of nearly 250-fold for 3 and over 30-fold for 4. Affinities and selectivities were univocally assessed through the BC50 descriptor, for which a generalized treatment is described that extends the scope of the descriptor to include any two-reagent host-guest system featuring any number of binding constants. ITC titrations of betaGlc in acetonitrile evidenced, for both receptors, a strong enthalpic contribution to the binding interaction, suggesting multiple H bonding. Selectivity trends toward alphaGlc and betaGlc analogous to those obtained in solution were also observed in the gas phase for 3 and 4 by collision-induced dissociation experiments. From comparison with appropriate reference compounds, a substantial contribution to carbohydrate binding emerged for both the imino/amino and the pyrrolic H-bonding groups but not for the amidic group. This previously undocumented behavior, supported by crystallographic evidence, has been discussed in terms of geometric, functional, and coordinative complementarity between H-bonding groups and glycosidic hydroxyls and opens the way to a new designer strategy of H-bonding receptors for carbohydrates.
authors.affiliation: Dipartimento di Chimica Organica, Centro Risonanze Magnetiche (CERM), Università di Firenze, Firenze, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
authors.forename: Martina
authors.initials: M
authors.lastname: Cacciarini
authors.forename: Oscar
authors.initials: O
authors.lastname: Francesconi
authors.forename: Alberto
authors.initials: A
authors.lastname: Vacca
authors.forename: Gloriano
authors.initials: G
authors.lastname: Moneti
authors.forename: Andrea
authors.initials: A
authors.lastname: Ienco
authors.forename: Stefano
authors.initials: S
authors.lastname: Roelens
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D006027:Glycosides / Q000737:chemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D017186:Titrimetry
chemical_list: D006027:Glycosides; D009005:Monosaccharides; D011758:Pyrroles