Chiral Diaminopyrrolic Receptors for Selective Recognition of Mannosides, Part 2: A 3D View of the Recognition Modes by X‐ray, NMR Spectroscopy, and Molecular Modeling

Abstract

The structural features of a representative set of five complexes of octyl α- and β-mannosides with some members of a new generation of chiral tripodal diaminopyrrolic receptors, namely, (R)-5 and (S)- and (R)-7, have been investigated in solution and in the solid state by a combined X-ray, NMR spectroscopy, and molecular modeling approach. In the solid state, the binding arms of the free receptors 7 delimit a cleft in which two solvent molecules are hydrogen bonded to the pyrrolic groups and to the benzenic scaffold. In a polar solvent (CD(3)CN), chemical shift and intermolecular NOE data, assisted by molecular modeling calculations, ascertained the binding modes of the interaction between the receptor and the glycoside for these complexes. Although a single binding mode was found to adequately describe the complex of the acyclic receptor 5 with the α-mannoside, for the complexes of the cyclic receptors 7 two different binding modes were required to simultaneously fit all the experimental data. In all cases, extensive binding through hydrogen bonding and CH-π interactions is responsible for the affinities measured in the same solvent. Furthermore, the binding modes closely account for the recognition preferences observed toward the anomeric glycosides and for the peculiar enantiodiscrimination properties exhibited by the chiral receptors.

Antiviral Activity of Synthetic Aminopyrrolic Carbohydrate Binding Agents: Targeting the Glycans of Viral gp120 to Inhibit HIV Entry

“…[11] The progenitor of this family is the tripodal aminopyrrolic receptor 1 the structure of which interestingly presents close similarities with the architecture of the primary mannose binding site of PRM-A, as suggested by Ito and Nakagawa (Scheme 1). [12a,b] In order to evaluate the efficacy of these receptors as CBAs, we have recently tested their biological activity toward several strains of yeast and yeast-like microorganisms, which present ac losec arbohydrate similarity between the mannan portion exposed on their cell surface and the oligomannoseg lycans of the gp120 glycoprotein of the viral envelope of HIV.…”

Synthetic aminopyrrolic receptors have apoptosis inducing activity

“…1) were prepared according to previously described procedures. 17 This series of compounds was chosen so as to span a range of supramolecular recognition space. Specifically, it includes synthetic receptors whose octyl mannoside binding affinities are low ( 1 , 5 ), moderate ( 2–4 ) and high ( 6 , 7 ) (Table S1†).…”

“…17 Some of the compounds in question were found to possess antibiotic activity, an effect rationalized in terms of an ability to bind to cell-surface glycans thereby interfering with key cellular processes. 17 a Recognizing the potential link between antibiotic and anticancer activity that might exist for synthetic, mannoside-recognizing receptors, we decided to conduct an investigation of the effect of these wholly synthetic receptors on cell viability.…”

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

“…In 2011, Roelens’ group [11–13] synthetized and tested a chiral diaminopyrrolic tripodal receptor that showed high binding affinities to mannosides (Fig. 1).…”

“…This particular receptor is significantly more active in acetonitrile (ACN) than in water [14]. In fact, this receptor family [11–13] could only be tested in water at slightly acidic conditions, due to solubility reasons, and proved to be very inefficient [14]. Unraveling the molecular details of these host–guest interactions is crucial to understand their different performances when changing the solvent and to identify the molecular determinants behind the reported high affinities.…”