Template‐Directed Quantitative One‐Pot Synthesis of Homochiral Helical Receptors Enabling Enantioselective Binding

Abstract

Template‐directed synthesis and dynamic covalent chemistry were implemented to achieve quantitative one‐pot syntheses of homochiral helical cavities inside aromatic foldamers. One‐handed helical receptors P‐1, M‐1, P‐2 and M‐2 were assembled from their precursors in the presence of appropriate templates (d‐ and l‐tartaric acid, and d‐ and l‐sorbitol, respectively) via three sequential steps in one pot: imine‐linked chain elongation, template‐induced folding and [4+2] cycloaddition between helical turns. These helical receptors were proven to enantioselectively bind chiral guests used as the templates, and the differences between the association constants of enantiomeric guests were up to more than two orders of magnitude. The structures and binding modes of the receptors were fully characterized by single‐crystal X‐ray crystallography and 1H NMR spectroscopy.

Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein–Ligand Interactions

“…In order to explore the correlations of the binding strength (K a ) and properties of guest fragments, molecular descriptors including the logarithm of the octanol:water partition coe cient (log P), dipole moment (μ), molecular volume (V), surface area (S), and asphericity Ω a ) were collected 16,27 . ] and aldehydes (7-9), esters (10-12) and acids (13)(14)(15) were smaller compared with those of amines (1-3) and alcohols (4)(5)(6). The large binding constants between the host and fragments 1-6 re ected stronger binding interaction originated from the H-bond accepting ability of the nitrogen atom of aliphatic amines or the oxygen atom of aliphatic alcohol 32-34 .…”

“…Binding of fragments to endo-[P4-(OH)BPO]. Recently, several biomimetic pockets with polar binding sites in their hydrophobic pockets have been disclosed [11][12][13][14][15][16][17][18] . Impressively, thermodynamics of interactions between biomimetic pockets and guests in water has been studied systematically by Jiang and coworkers [16][17][18] , which is highly valuable as the recognizations of ligands by protein binding pockets occur in aqueous environment in living systems.…”

“…To this end, there have been reports on pocket-shaped receptors, such as cavitands 11 , glucose receptor 2 12 , aryl-extended calix [4]pyrrole receptors 13 , helical aromatic and oligoamide foldamers (Fig. 1a-e) 14,15 . Jiang's group recently made signi cant progress in transforming naphthalene-based tubular molecules into biomimetic tubes in which the inwardly directed functional groups improved their binding a nity and selectivity toward fragment ligands (Fig.…”

“…We rst assessed the binding between [P4-(OH)BPO] and fragments including alkyl amines, alcohols, aldehydes, acids, and esters (Table1). The formation of fragmentpocket complexes between [P4-(OH)BPO] and the guests was evidenced by obvious up eld shifting of the proton signals of a-carbons of the guests(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) in the 1 H NMR spectra of the fragment-pocket pairs in a 1∶1 molar ratio in non-polar solvent. As shown in the 1 H NMR spectra (Fig.4), upon mixing n-butyric acid(13) and [P4-BPO(1-OH)] in CDCl 3 , obvious up eld shifts for the methylene (Δδ α = -0.26 ppm and Δδ β = -0.25 ppm) and the terminal methyl (Δδ γ = -0.14 ppm) proton signals of were observed.…”

Photon-gated foldaxane assembly/disassembly

“…Aromatic oligoamide foldamers have emerged as a versatile class of functional molecules, which adopt robust folded conformations whose properties can be finely tuned based on the chosen sequence of monomers. 1 Judicious design of such foldamers has been shown to offer cavities for strong and selective binding of a range of guest molecules 2 and, more recently, photoactivity has been introduced both in terms of emission and photoreaction. 3 Foldaxanes, 4,5 supramolecular architectures comprising aromatic helices on a linear molecular axle, represent a recent addition to the field of interpenetrating molecules.…”