Sebastian Beil

A polyaromatic cavity : The exclusive binding of a monounsaturated fatty acid from a mixture with the corresponding saturated substrate was demonstrated by an artificial polyaromatic receptor in water. Competitive binding experiments revealed higher binding affinity of the receptor for oligo‐ and polyunsaturated fatty acids (see picture). Within the receptor, the biosubstrates were stabilized against air, light, and heat owing to the polyaromatic shielding effect.

Abstract

Selective recognition of natural fatty acids is intrinsically difficult owing to the long, flexible, and poorly interactive hydrocarbon chains. Inspired by biological recognition systems, we herein demonstrate the exclusive binding of a monounsaturated fatty acid by an artificial polyaromatic receptor from a mixture of the unsaturated and corresponding saturated substrates (i.e., oleic and stearic acids) in water. The selectivity stems from multiple CH–π/π–π interactions between the host framework and the guest in its roughly coiled conformation. Moreover, competitive binding experiments elucidate higher binding affinities of the receptor for oligo‐ and polyunsaturated fatty acids (e.g., α‐linolenic acid and EPA). Within the receptor, the biosubstrates are remarkably stabilized against air, light, and heat owing to the polyaromatic shielding effect.

An integrated molecular machine setup allows the transmission of potential energy from a motor unit onto a covalently connected, distant, and sterically strongly encumbered biaryl receiver. By action of the motor unit, single‐bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally.

Abstract

Light‐driven molecular motors possess immense potential as central driving units for future nanotechnology. Integration into larger molecular setups and transduction of their mechanical motions represents the current frontier of research. Herein we report on an integrated molecular machine setup allowing the transmission of potential energy from a motor unit onto a remote receiving entity. The setup consists of a motor unit connected covalently to a distant and sterically encumbered biaryl receiver. By action of the motor unit, single‐bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally. The transmitted potential energy is directly measured as the extent to which energy degeneration is lifted in the thermal atropisomerization of this biaryl. Energy degeneracy is reduced by more than 1.5 kcal mol⁻¹, and rate accelerations of several orders of magnitude in terms of the rate constants are achieved.

A 2,6‐anthrylene‐linked bis(m‐terphenylcarboxylic acid) strand forms a one‐handed homo double helix induced by chiral amines, thereby producing the chiral anti‐photodimer with up to 98 % enantiomeric excess upon photoirradiation. The chirality of the anti‐photodimer can be readily controlled by the chirality of the chiral amines.

Abstract

A novel 2,6‐anthrylene‐linked bis(m‐terphenylcarboxylic acid) strand (1) self‐associates into a racemic double‐helix. In the presence of chiral mono‐ and diamines, either a right‐ or left‐handed double‐helix was predominantly induced by chiral amines sandwiched between the carboxylic acid strands with accompanying stacking of the two prochiral anthracene linker units in an enantiotopic face‐selective way, as revealed by circular dichroism and NMR spectral analyses. The photoirradiation of the optically active double helices complexed with chiral amines proceeded in a diastereo‐ (anti or syn) and enantiodifferentiating way to afford the chiral anti‐photodimer with up to 98 % enantiomeric excess when (R)‐phenylethylamine was used as a chiral double‐helix inducer. The resulting optically active anti‐photodimer can recognize the chirality of amines and diastereoselectively complex with chiral amines.

Chiral‐featured materials fabricated with the supramolecular nanoarchitectonics concept are discussed. Chiral features and functions are considered with various supramolecular materials, including metal–organic frameworks and liquid crystals. Amplification of chiral molecular information from a molecule to material‐level structures and the creation of chirality from achiral components upon temporal statistic fluctuations are universal, regardless of nature of assemblies.

Abstract

Exploration of molecular functions and material properties based on the control of chirality would be a scientifically elegant approach. Here, the fabrication and function of chiral‐featured materials from both chiral and achiral components using a supramolecular nanoarchitectonics concept are discussed. The contents are classified in to three topics: i) chiral nanoarchitectonics of rather general molecular assemblies; ii) chiral nanoarchitectonics of metal–organic frameworks (MOFs); iii) chiral nanoarchitectonics in liquid crystals. MOF structures are based on nanoscopically well‐defined coordinations, while mesoscopic orientations of liquid‐crystalline phases are often flexibly altered. Discussion on the effects and features in these representative materials systems with totally different natures reveals the universal importance of supramolecular chiral nanoarchitectonics. Amplification of chiral molecular information from molecules to materials‐level structures and the creation of chirality from achiral components upon temporal statistic fluctuations are universal, regardless of the nature of the assemblies. These features are thus surely advantageous characteristics for a wide range of applications.

Labeling on demand: Spatiotemporal control over click reactions, which are widely applied in (bio)chemical research, opens up new strategies for their application to small‐molecule systems and (bio)macromolecules. In an effective supramolecular approach, a copper(I)–N‐heterocyclic carbene click catalyst was inhibited through encapsulation by cucurbit[7]uril and activated by its release by chemical signals (see picture).

Abstract

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on‐demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper‐catalyzed click chemistry, on small molecules as well as protein targets.

Keep ’em separated: A simple and energy‐efficient separation method, using nonporous adaptive crystals of cucurbit[6]uril, for toluene/pyridine mixtures is reported. The method has a high selectivity for pyridine and can remove even a small quantity of pyridine in the crude toluene stream.

Abstract

The production of high purity toluene and pyridine is of significance in both industrial production and synthetic chemistry. The present protocols available to separate toluene/pyridine mixtures are several energy‐intensive distillation methods, which are not environmentally friendly and cost‐effective. Herein, we provide an energy‐efficient and simple adsorptive separation protocol using nonporous adaptive crystals of cucurbit[6]uril (Q[6]). Q[6] crystals separate pyridine from toluene/pyridine mixtures with nearly 100 % purity. Furthermore, removal of the guest from guest‐loaded Q[6] leads to the guest‐free cucurbit[6]uril, which can be recycled without losing performance.

Quick as a F⁻lash: The use of Lewis acidic, water‐compatible phosphonium boranes is introduced for the quick and selective transport of F⁻ across biological membrane mimics.

Abstract

With the view of developing selective transmembrane anion transporters, a series of phosphonium boranes of general formula [p‐RPh₂P(C₆H₄)BMes₂]⁺ have been synthesized and evaluated. The results demonstrate that variation of the R group appended to the phosphorus atom informs the lipophilicity of these compounds, their Lewis acidity, as well as their transport activity. Anion transport experiments in POPC‐based large unilamellar vesicles show that these main‐group cations are highly selective for the fluoride anion, which is transported more than 20 times faster than the chloride anion. Finally, this work shows that the anion transport properties of these compounds are extremely sensitive to the steric crowding about the boron atom, pointing to the crucial involvement of the Group 13 element as the anion binding site.

aza‐BODIPY comes alive! Living supramolecular polymerization was demonstrated by aza‐BODIPY 1 bearing hydrogen‐bond accepting triazole units that can be facilely constructed through click chemistry. The H‐bonding unit of amide‐linked triazole in dye 1 could be employed as a general motif for encoding conformational information and developing polymorphic supramolecular systems.

Abstract

An aza‐BODIPY dye 1 bearing two hydrophobic fan‐shaped tridodecyloxybenzamide pendants through 1,2,3‐triazole linkages was synthesized by a click reaction and characterized. ¹H NMR studies indicated that dye 1 exhibited variable conformations through intramolecular H‐bonding interaction, which is beneficial for the polymorphism of aggregation. The thermodynamic, structural, and kinetic aspect of the supramolecular polymerization of dye 1 was investigated by UV/Vis absorption spectroscopy, IR spectroscopy, AFM, TEM, and SEM. Biphasic aggregation pathways of dye 1, leads to the formation of off‐pathway, metastable Agg. I and thermodynamically stable Agg. II with distinct H‐aggregation spectra and nanoscale morphology. The living manner of the supramolecular polymerization of dye 1 was demonstrated in seeded polymerization experiments with temperature‐modulated successive cooling–heating cycles.

Anthracene excited: Supramolecular photocatalysis via charge‐transfer excitation of a host–guest complex was realized by use of macrocyclic boronic ester [2+2] _BTH‐F containing highly electron‐deficient difluorobenzothiadiazole moieties. The triplet excited state of anthracene was generated by visible light irradiation, and cycloaddition with several dienes and alkenes proceeded in high yields.

Abstract

Supramolecular photocatalysis via charge‐transfer excitation of a host–guest complex was developed by use of the macrocyclic boronic ester [2+2]_BTH‐F containing highly electron‐deficient difluorobenzothiadiazole moieties. In the presence of a catalytic amount of [2+2]_BTH‐F, the triplet excited state of anthracene was generated from the charge‐transfer excited state of anthracene@[2+2]_BTH‐F by visible‐light irradiation, and cycloaddition of the excited anthracene with several dienes and alkenes proceeded in a [4+2] manner in high yields.

Clamping down on DNA damage: Direct measurement of NTH1 glycosylase activity is of interest for the study of this DNA repair pathway and related diseases. A DNA‐probe design for glycosylase activity is reported that relies on a “clamp” of pyrenes and shows a robust ratiometric response. The activity of NTH1 is measured both in vitro and in cell lysates, and a selective inhibitor of NTH1 is identified by high‐throughput screening.

Abstract

Direct measurement of DNA repair enzyme activities is important both for the basic study of cellular repair pathways as well as for potential new translational applications in their associated diseases. NTH1, a major glycosylase targeting oxidized pyrimidines, prevents mutations arising from this damage, and the regulation of NTH1 activity is important in resisting oxidative stress and in suppressing tumor formation. Herein, we describe a novel molecular strategy for the direct detection of damaged DNA base excision activity by a ratiometric fluorescence change. This strategy utilizes glycosylase‐induced excimer formation of pyrenes, and modified DNA probes, incorporating two pyrene deoxynucleotides and a damaged base, enable the direct, real‐time detection of NTH1 activity in vitro and in cellular lysates. The probe design was also applied in screening for potential NTH1 inhibitors, leading to the identification of a new small‐molecule inhibitor with sub‐micromolar potency.

Hierarchical supramolecular chiral liquid‐crystalline polymer assemblies are highly challenging to construct in situ in a controlled manner. Here, we report polymerization‐induced chiral self‐assembly (PICSA) for the first time, by which hierarchical supramolecular chiral azobenzene‐containing block copolymer (Azo‐BCP) assemblies were constructed in a controlled manner, not only for different morphologies but also for chiroptical properties, with π‐π stacking interactions occurring in the layered structure of Azo smectic phases. The evolution of chirality from terminal alkyl chain to Azo mesogen building blocks and further induction of supramolecular chirality in BCP liquid‐crystalline assemblies during PICSA process is achieved. A full spectrum of morphologies spanning spheres, worms, helical fibers, lamellae and vesicles were observed and the morphological transition had a crucial effect on the chiral expression of Azo‐BCP assemblies. The supramolecular chirality of Azo‐BCP assemblies destroyed by 365 nm UV light irradiation can be fully recovered by heating‐cooling treatment and this dynamic reversible achiral‐chiral switch can be repeated at least five times. The PICSA process provides a novel platform for effectively producing photoresponsive hierarchical supramolecular chiral polymer assemblies in situ with various morphologies in a well‐controlled manner.

Topologically controlled ligands with a family of tetrahedral DNA frameworks (TDFs) were generated through the formation of 0‐simplex to 3‐simplex, and to simplicial complex. The multiple ligands are stoichiometrically and topologically arranged to allow the tuning of the binding strength between ligands and receptors as validated with cell sorting.

Abstract

Molecular recognition in cell biological process is characterized with specific locks‐and‐keys interactions between ligands and receptors, which are ubiquitously distributed on cell membrane with topological clustering. Few topologically‐engineered ligand systems enable the exploration of the binding strength between ligand‐receptor topological organization. Herein, we generate topologically controlled ligands by developing a family of tetrahedral DNA frameworks (TDFs), so the multiple ligands are stoichiometrically and topologically arranged. This topological control of multiple ligands changes the nature of the molecular recognition by inducing the receptor clustering, so the binding strength is significantly improved (ca. 10‐fold). The precise engineering of topological complexes formed by the TDFs are readily translated into effective binding control for cell patterning and binding strength control of cells for cell sorting. This work paves the way for the development of versatile design of topological ligands.

Big, handed, super ! An efficient synthesis of benzidine/quinoidal benzidine‐linked, superbenzene‐based fully conjugated macrocycles and cage‐like cyclophanes has been developed. These show chiral optical properties, paramagnetic activity, and topology‐dependent electronic properties, dynamic behavior, and host–guest chemistry.

Abstract

Synthesis of fully conjugated cyclophanes containing large‐size polycyclic aromatics is challenging. Now, three benzidine‐linked, hexa‐peri‐hexabenzocoronene (superbenzene)‐based ortho‐, para‐, and meta‐cyclophanes are synthesized through intermolecular Yamamoto coupling reaction of structurally pre‐organized precursors. Subsequent oxidative dehydrogenation gave the corresponding quinoidal benzidine‐linked cyclophanes. Their geometries were confirmed by X‐ray crystallographic analysis and their electronic properties were investigated by electronic absorption, cyclic voltammetry, and DFT calculations. The quinoidal benzidine‐linked cyclophanes show thermally populated paramagnetic activity with a relatively large singlet‐triplet energy gap. Two enantiomers for the ortho‐cyclophanes (1‐NH and 1‐N ) were isolated and their chiral figure‐of‐eight macrocyclic structures were identified. The cage‐like cyclophanes 2‐NH and 3‐NH with concave surface can selectively encapsulate fullerene C₇₀.

The next generation: Recent developments made in the field of pillar[n]arene‐based macrocyclic molecules to go beyond single macrocyclic structures with two alkoxy substituents on every benzene ring are highlighted. The recently introduced tiara[n]arenes, leaning pillar[n]arenes, and BowtieArenes with incomplete alkoxy substitution may be regarded as a next step in the structural diversification of pillar[n]arenes.

Abstract

Despite the fact that pillar[n]arenes receive major interest as building blocks for supramolecular chemistry and advanced materials, their functionalization is generally limited to the modification of the hydroxy or alkoxy units present on the rims. This limited structural freedom restricts further developments and has very recently been overcome. In this article, we highlight three very recent studies demonstrating further structural diversification of pillar[n]arenes by partial removal of the alkoxy substituents on the rims, which can be considered as the next generation of pillar[n]arenes.

Simple self‐assembly methods cannot be used to attain high‐level organizations such as those found in biological systems. The introduction of non‐equilibrium processes and harmonization of multiple actions is required. As a novel methodology beyond self‐assembly, nanoarchitectonics, whose main conceptual aim is the formation of functional materials from nanoscopic units through the fusion of different scientific disciplines, has been proposed for the creation of bio‐like high functionality hierarchically organized structures.

Abstract

Incorporation of non‐equilibrium actions in the sequence of self‐assembly processes would be an effective means to establish bio‐like high functionality hierarchical assemblies. As a novel methodology beyond self‐assembly, nanoarchitectonics, which has as its aim the fabrication of functional materials systems from nanoscopic units through the methodological fusion of nanotechnology with other scientific disciplines including organic synthesis, supramolecular chemistry, microfabrication, and bio‐process, has been applied to this strategy. The application of non‐equilibrium factors to conventional self‐assembly processes is discussed on the basis of examples of directed assembly, Langmuir–Blodgett assembly, and layer‐by‐layer assembly. In particular, examples of the fabrication of hierarchical functional structures using bio‐active components such as proteins or by the combination of bio‐components and two‐dimensional nanomaterials, are described. Methodologies described in this review article highlight possible approaches using the nanoarchitectonics concept beyond self‐assembly for creation of bio‐like higher functionalities and hierarchical structural organization.

Chiral cations have been used extensively as organocatalysts, but their application to rendering transition metal–catalyzed processes enantioselective remains rare. This is despite the success of the analogous charge-inverted strategy in which cationic metal complexes are paired with chiral anions. We report here a strategy to render a common bipyridine ligand anionic and pair its iridium complexes with a chiral cation derived from quinine. We have applied these ion-paired complexes to long-range asymmetric induction in the desymmetrization of the geminal diaryl motif, located on a carbon or phosphorus center, by enantioselective C–H borylation. In principle, numerous common classes of ligand could likewise be amenable to this approach.

Self‐assembly is a bioinspired strategy to create soft materials for renewable and clean energy technologies. The field of supramolecular energy materials is described, covering work on self‐assembling molecules to craft light harvesting systems for photocatalysis and photovoltaics. Also, pathways to use supramolecular phases as templates for inorganic structures and electrodeposition for the synthesis of energy materials are discussed.

Abstract

Self‐assembly is a bioinspired strategy to craft materials for renewable and clean energy technologies. In plants, the alignment and assembly of the light‐harvesting protein machinery in the green leaf optimize the ability to efficiently convert light from the sun to form chemical bonds. In artificial systems, strategies based on self‐assembly using noncovalent interactions offer the possibility to mimic this functional correlation among molecules to optimize photocatalysis, photovoltaics, and energy storage. One of the long‐term objectives of the field described here as supramolecular energy materials is to learn how to design soft materials containing light‐harvesting assemblies and catalysts to generate fuels and useful chemicals. Supramolecular energy materials also hold great potential in the design of systems for photovoltaics in which intermolecular interactions in self‐assembled structures, for example, in electron donor and acceptor phases, maximize charge transport and avoid exciton recombination. Possible pathways to integrate organic and inorganic structures by templating strategies and electrodeposition to create materials relevant to energy challenges including photoconductors and supercapacitors are also described. The final topic discussed is the synthesis of hybrid perovskites in which organic molecules are used to modify both structure and functions, which may include chemical stability, photovoltaics, and light emission.

Send reinforcements : Binding affinities between foldamer‐based receptors and anions are greatly reinforced by π‐stacking within the receptors. The association constant increases by more than three orders of magnitude when N(CH₃)₂ is replaced with NO₂, despite both complexes forming five identical hydrogen bonds.

Abstract

As a synthetic model for intra‐protein interactions that reinforce binding affinities between proteins and ligands, the energetic interplay of binding and folding was investigated using foldamer‐based receptors capable of adopting helical structures. The receptors were designed to have identical hydrogen‐bonding sites for anion binding but different aryl appendages that simply provide additional π‐stacking within the helical backbones without direct interactions with the bound anions. In particular, the presence of electron‐deficient aryl appendages led to dramatic enhancements in the association constant between the receptor and chloride or nitrate ions, by up to three orders of magnitude. Extended stacking within the receptor contributes to the stabilization of the entire folding structure of complexes, thereby enhancing binding affinities.