Molecular Recognition in Water Using Macrocyclic Synthetic Receptors

Abstract

Molecular recognition in water using macrocyclic synthetic receptors constitutes a vibrant and timely research area of supramolecular chemistry. Pioneering examples on the topic date back to the 1980s. The investigated model systems and the results derived from them are key for furthering our understanding of the remarkable properties exhibited by proteins: high binding affinity, superior binding selectivity, and extreme catalytic performance. Dissecting the different effects contributing to the proteins' properties is severely limited owing to its complex nature. Molecular recognition in water is also involved in other appreciated areas such as self-assembly, drug discovery, and supramolecular catalysis. The development of all these research areas entails a deep understanding of the molecular recognition events occurring in aqueous media. In this review, we cover the past three decades of molecular recognition studies of neutral and charged, polar and nonpolar organic substrates and ions using selected artificial receptors soluble in water. We briefly discuss the intermolecular forces involved in the reversible binding of the substrates, as well as the hydrophobic and Hofmeister effects operating in aqueous solution. We examine, from an interdisciplinary perspective, the design and development of effective water-soluble synthetic receptors based on cyclic, oligo-cyclic, and concave-shaped architectures. We also include selected examples of self-assembled watersoluble synthetic receptors. The catalytic performance of some of the presented receptors is also described. The latter process also deals with molecular recognition and energetic stabilization, but instead of binding ground-state species, the targets become elusive counterparts: transition states and other high-energy intermediates.

Lower‐Rim‐Modified Calix[4]arene‐Pyrrolotetrathiafulvalene Molecular Tweezers

“…Thus, we have demonstrated that (i) conjugate 2 can serve as a precursor to MPTTF-calix [4]arene molecular tweezers with different substituents on the calixarene lower rim and (ii) propargylated derivative 4 can be modified using the click reaction with various substituents bearing an azide group, which makes compound 4 another universal precursor in the synthesis of modified MPTTF-calix[4]arene receptors. In future, functionalities attached to the lower rim can be used, for example, for solubilization of the receptors in aqueous media [20] or for their attachment onto surfaces e. g. for sensing applications. [21] Electrochemical properties of new bis-MPTTF molecular tweezers have been investigated by means of cyclic voltammetry (CV) in dichloromethane/Bu 4 NClO 4 solution (Figure 2).…”

Self-assembly of a water-soluble endohedrally functionalized coordination cage including polar guests

“…The inclusion geometry of the 52 4+ complex diminishes the aromatic surface of the receptor available to water solvation. Because the binding of non-polar residues in water is mainly driven by the hydrophobic effect (HE), 38,43 the reduction in aromatic surface helps explain the lower aggregation tendency of the 52 4+ complex compared to the free receptor 2 4+ . The addition of ca.…”

“…All the polar guests used are difficult to bind in water solution with other synthetic receptors. 38,39,40 Using 1 H NMR spectroscopy, we study the conformational arrangement adopted by the end formyl groups of the α,ω-bis-formamides included in the [2•Pd] 6+ CC. We disclose solid-state structures for analogous inclusion complexes with the organic-soluble [1a•Pd] 2+ CC.…”

Hydrolysis of Aliphatic Bis‐isonitriles in the Presence of a Polar Super Aryl‐Extended Calix[4]pyrrole Container

“…We calculated large and negative heat capacity values (DC p )f or all binding processes.T his result indicates that the formation of the complexes, 2b-4b&1,i sm ainly driven by the hydrophobic effect. [34,35] Based on the above,w eh ypothesized that in the 2b&1 complex, the rate of the hydrolysis reaction producing the mono-formamide 3b should be different from that in the bulk solution.…”