Pyrrolic Tripodal Receptors Effectively Recognizing Monosaccharides. Affinity Assessment through a Generalized Binding Descriptor

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 β-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 βGlc in acetonitrile evidenced, for both
receptors, a strong enthalpic contribution to the binding interaction, suggesting multiple H bonding. Selectivity
trends toward αGlc and βGlc 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.