Molecular Recognition of Hydrophilic Molecules in Water by Combining the Hydrophobic Effect with Hydrogen Bonding

Abstract

During the last half a century, great achievements have been made in molecular recognition in parallel with the invention of numerous synthetic receptors. However, the selective recognition of hydrophilic molecules in water remains a generally accepted challenge in supramolecular chemistry but is commonplace in nature. In an earlier Communication [J. Am. Chem. Soc.201613814550], we reported a pair of endo-functionalized molecular tubes that surprisingly prefer highly hydrophilic molecules over hydrophobic molecules of a similar size and shape. The hydrophobic effect and hydrogen bonding were proposed to be responsible, but their exact roles were not fully elucidated. In this Article, we present a thorough study on the binding behavior of these molecular tubes toward 44 hydrophilic molecules in water. Principal component analysis reveals that the binding strength is weakly correlated to the hydrophobicity, volume, surface area, and dipole moment of guests. Furthermore, molecular dynamics simulations show the hydrophobic effect through releasing the poorly hydrogen-bonded cavity water contributes to the binding of all the hydrophilic molecules, while hydrogen bonding differentiates these molecules and is thus the key to achieve a high selectivity toward certain hydrophilic molecules over other molecules with a similar size and shape. Therefore, a good guest for these molecular tubes should meet the following criteria: the hydrogen-bonding sites should be complementary, and the molecular volume should be large enough to expel all the cavity water but not too large to cause steric hindrance. This rule of thumb may also be used to design a selective receptor for certain hydrophilic molecules. Following these guidelines, a “best-fit” guest was found for the syn-configured molecular tube with a binding constant as high as 106 M–1.

Tuning Solvent Miscibility: A Fundamental Assessment on the Example of Induced Methanol/n-Dodecane Phase Separation

“…This may be the reason why experimentally we have found that the amount of n -dodecane in the bottom phase of the MLDT system is lower than in the MDT system, with the amount of tri- n -butyl phosphate being the same, since tri- n -butyl phosphate can be part of the hydrogen-bond network, and consequently the exclusion of n -dodecane is not due to the direct presence of LiCl, but due to the “hardening” of the hydrogen-bond network. This effect recalls what had been previously observed by Jiang et al 48 while studying the roles of the hydrophobic effect and hydrogen bonding in systems able to selectively recognize hydrophilic molecules in water. Following the concept that it is not the addition of the salt that directly improves the phase separation, but rather a consequence of the hydrogen-bond network, new ways of improving phase separation of two solvents can be thought and tested.…”

Selective Recognition of Phenazine by 2,6‐Dibutoxylnaphthalene‐Based Tetralactam Macrocycle

“…During the last six years, we reported a series of naphthol‐ based macrocyclic receptors which have been used in molecular recognition, molecular sensing, molecular machine, cooperative self‐assembly and supramolecular hydrogel . We recently synthesized a tetralactam macrocycle with 2,3‐dibutoxylnaphthalene .…”

BODIPY- and Porphyrin-Based Sensors for Recognition of Amino Acids and Their Derivatives

“…As a result, a different behaviour, especially the optical response, can be used to monitor the presence of the target molecule in the medium that is tested. Molecular recognition is a specific tendency of compounds to selectively bind to each other through non-covalent interactions [ 1 , 2 , 3 ], such as metal coordination [ 4 ], hydrogen bonding [ 5 ], hydrophobic interactions [ 6 ], van der Waals interactions [ 7 ], π–π stacking [ 8 ] or electrostatic interactions [ 9 ]. The term “chiral recognition” refers to an event of molecular recognition, in which a receptor exhibits higher affinity towards one of existing enantiomers of guest molecule.…”