1,3,5-2,4,6-Functionalized Benzene Molecular Cage: An Environmentally Responsive Scaffold that Supports Hierarchical Superstructures.

New stimulus responsive scaffolds are of interest as constituents of hierarchical supramolecular ensembles. 1,3,5-2,4,6-Functionalized, facially segregated benzene moieties have a time-honored role as building blocks for host molecules. However, their user as switchable motifs in the construction of multi-component supramolecular structures remains poorly explored. Here, we report a molecular cage 1, which consists of a bent anthracene dimer 3 paired with 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene 2. As the result of the pH-induced ababab ↔ bababa isomerization of the constituent functionalized benzene units derived from 2, this cage can reversibly convert between an open state and a closed form, both in solution and in the solid state. Cage 1 was used to create stimuli-responsive hierarchical superstructures, viz. Russian doll-like complexes with [K⊂18-crown-6⊂1]+ and [K⊂cryptand-222⊂1]+. The reversible assembly and disassembly of these superstructures could be induced by switching cage 1 from its open to closed form. The present study thus provides an unusual example where pH-triggered conformation motion within a cage-like scaffold is used to control the formation and disassociation of hierarchical ensembles.

Water and Air Stable Copper(I) Complexes of Tetracationic Catenane Ligands for Oxidative C-C Cross-Coupling.

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

Tetralactam macrocycle based indicator displacement assay for colorimetric and fluorometric dual-mode detection of urinary uric acid.

An indicator displacement assay for colorimetric and fluorometric dual-mode detection of urinary uric acid (UA) was constructed using a water-soluble naphthalene-based tetralactam macrocycle and the phenoxazine dye, resorufin (RF). The visual detection of UA levels of volunteers was successfully realized using modified paper assays, which could be used for the home monitoring of urinary UA.

The Influence of Small Biomolecules, Salts and Buffers on the Molecular Recognition of Amide Naphthotube in Aqueous Solutions.

We found the binding affinities of amide naphthotube to neutral organic molecules in water are not influenced by most of small biomolecules, inorganic salts, and PBS and Tris buffers but are reduced in HEPES buffer through competitive binding. Nevertheless, salts do change the binding affinities of amide naphthotube to charged molecules through a screening effect.

Switchable bifunctional molecular recognition in water using a pH-responsive Endo-functionalized cavity.

The construction of water-soluble synthetic hosts with a stimuli-responsive endo-functionalized cavity is challenging. These hosts feature a switchable cavity and may bring new properties to the fields of self-assembly, molecular machines, and biomedical sciences. Herein, we report a pair of water-soluble naphthotubes with a pH-responsive endo-functionalized cavity. The inward-directing secondary amine group of the hosts can be protonated and deprotonated. Thus, the hosts have different cavity features at the two states and show drastically different binding preference and selectivity in water. We reveal that the binding difference of the two host states is originated from the differences in charge repulsion, hydrogen bonding and the hydrophobic effects. Moreover, the guest binding can be easily switched in a ternary mixture with two guest molecules by adjusting the pH value of the solution. These pH-responsive hosts may be used for the construction of smart self-assembly systems and water-soluble molecular machines.

Circular Dichroism Based Chirality Sensing with Supramolecular Host-Guest Chemistry.

Optical methods are promising to address the ever-increasing demands for chirality analysis in drug discovery and related fields because they are amenable to high-throughput screening. Circular dichroism-based chiroptical sensing using host-guest chemistry is especially appealing due to the fast equilibrium kinetics, wide substrate scope, and potential for sustainable development. In this Minireview, we give an overview on this emerging field. General aspects of molecular recognition and chirality transfer are analyzed. Chirality sensors are discussed by dividing them into three classes according to their structural features. Applications of these chirality sensors for chirality analysis of the products of asymmetric reactions and for the real-time monitoring of reaction kinetics are demonstrated with selected examples. Moreover, challenges and research directions in this field are also highlighted.

Molecular recognition and photoprotection of riboflavin in water by a biomimetic host.

A water-soluble tetralactam macrocycle with 2,6-diethoxynaphthalene groups as side walls is able to strongly bind riboflavin (Ka >107 M-1) in water through hydrogen bonding and the hydrophobic effect. The encapsulated riboflavin can be stabilized by the host against photo-degradation under UV-vis irradiation, which may be harnessed to extend the shelf life of riboflavin.

Biomimetic Recognition of Quinones in Water by an Endo-Functionalized Cavity with Anthracene Sidewalls.

Selective molecular recognition in water is the foundation of numerous biological functions but is a challenge for most synthetic hosts. We employ the concept of endo-functionalized cavity and the strategy of simultaneous construction to address this issue. The concept and the strategy were demonstrated in the construction of a biomimetic host for selectively recognizing quinones in water. The host was synthesized by joining two pieces of bent anthracene dimer through amide bond formation, affording a deep hydrophobic cavity and inward-directing hydrogen bonding sites. The host can recognize quinones over their close analogues in water, and its association affinity to p-benzoquinone is the highest among all the known hosts and is even comparable to that of the bioreceptor. The binding with an anthraquinone reaches nanomolar affinity. Shielded hydrogen bonding, C-H⋅⋅⋅π, and charge transfer interactions, and the hydrophobic effect are responsible for the high binding affinity and selectivity.

Self-assembly of two-dimensional structures in water from rigid and curved amphiphiles with a low molecular weight.

Two-dimensional structures in water were self-assembled from rigid and curved amphiphiles with very low molecular weight (MW < 500 Da). The amphiphiles contain a bisnaphthalene core. Their structures have been characterized using 1H NMR spectroscopy, SEM, TEM, AFM, and DLS. The driving force was mainly attributed to hydrophobic effects.

Allosteric cooperativity in ternary complexes with low symmetry.

Two new naphthotubes with ester linkers were synthesized and characterized. With the syn isomers of an ester naphthotube and an ether naphthotube, strong positive allosteric cooperativity in a ternary complex with two different hosts on one guest was achieved. This paves the way to construct robust supramolecular architectures with high complexity and diversity.