A New Tripodal Receptor for Molecular Recognition of Monosaccharides. A Paradigm for Assessing Glycoside Binding Affinities and Selectivities by ¹H NMR Spectroscopy

Abstract

A new tripodal receptor for the recognition of monosaccharides is described. The prototypical host 1 features a 1,3,5-substituted 2,4,6-triethylbenzene scaffold bearing three convergent H-bonding units. The binding ability of the t-octyl derivative 1a toward a set of octylglycosides of biologically relevant monosaccharides, including Glc, Gal, Man, and GlcNAc, was investigated by 1H NMR in CDCl3. A protocol for the correct evaluation of binding affinities was established, which can be generally applied for the recognition of monosaccharides by 1H NMR spectroscopy. A three-constant equilibrium model, including 1:1 and 2:1 host-guest association and dimerization of the receptor, was ascertained for the interaction of 1a with all the investigated glycosides. An affinity index, which we defined median binding concentration BC50 in analogy to the IC50 parameter, intended to address the general issue of comparing dimensionally heterogeneous binding data, and a limiting BC0(50)quantity describing intrinsic binding affinities were developed for evaluating the results. BC0(50) values for 1a range from 1 to 6 mM, indicating an intrinsic binding affinity in the millimolar range and a selectivity factor of 5 toward the investigated glycosides. The treatment has been extended to include any generic host-guest system involved in single or multiple binding equilibria.

Bindungsmechanismen in supramolekularen Komplexen

“…[48] Wenn andere Komplexstöchiometrien außer der oft nur angenommenen 1:1-Zusammensetzung vorhanden sind, lässt sich die Effizienz einer Assoziation durch Angabe eines Affinitätsindex BC 50 skalieren, der in Analogie zum IC 50 die für eine 50-prozentige Komplexierung notwendige Konzentration des überwiegen-den Partners angibt. [49] Kompartimentalisierung: Eine wenig beachtete Möglich-keit, zwar nicht die Affinität, jedoch die Ansprechempfindlichkeit und damit z. B. die Detektionsgrenze für ein AnalytGastmolekül in sehr verdünntem Medium zu verbessern, besteht in der Kompartimentalisierung des Wirt-Gast-Systems.…”

Phenyl boronic acid complexes of diols and hydroxyacids

“…21,22 They propose a binding descriptor of the intrinsic median binding concentration (BC 50°) which can be derived from a knowledge of the formation constants of multiple complexes between a pair of reactant species. A similar approach has been employed by Reinhoudt and co-workers in the discussion of self-assembled complexes.…”

A biomimetic design for a sialylated, glycan-specific smart polymer

“…A clear upfield shift from 8.98 to 8.92 p.p.m. was observed for the amide-a H-proton of the dipeptide, which can be attributed to a hydrogen-bonding interaction, 30 whereas the terminal amine-b H-proton signal of the dipeptide gradually became weaker and finally disappeared when 1 equiv. of Neu5Ac was added, which might correspond to an acid-base reaction between the carboxyl group in Neu5Ac and the amine in the dipeptide.…”