Gold(I) Catalysis at Extreme Concentrations Inside Self‐Assembled Nanospheres

Homogeneous transition‐metal catalysis is a crucial technology for the sustainable preparation of valuable chemicals. The catalyst concentration is usually kept as low as possible, typically at mM or μM levels, and the effect of high catalyst concentration is hardly exploited because of solubility issues and the inherent unfavorable catalyst/substrate ratio. Herein, a self‐assembly strategy is reported which leads to local catalyst concentrations ranging from 0.05 M to 1.1 M , inside well‐defined nanospheres, whilst the overall catalyst concentration in solution remains at the conventional mM levels. We disclose that only at this high concentration, the gold(I) chloride is reactive and shows high selectivity in intramolecular C? O and C? C bond‐forming cyclization reactions.     

pH‐Switchable Self‐Assembled Materials

Self‐assembled materials, which are able to respond to external stimuli, have been extensively studied over the last decades. A particularly exciting stimulus for a wide range of biomedical applications is the pH value of aqueous solutions, since deprotonation‐protonation events are crucial for structural and functional properties of biopolymers. In living cells and tissues, intra‐ and extracellular pH values are stringently regulated, but can deviate from pH neutral as observed for example in tumorous, inflammatory sites, in endocytic pathways, and specific cellular compartments. By using a pH‐switch as a stimulus, it is thereby possible to address specific targets in order to cause a programmed response of the supramolecular material. This strategy has not only been successfully applied in fundamental research but also in clinical studies. In this feature article, current strategies that have been used in order to design materials with pH‐responsive properties are illustrated. This discussion only addresses selected examples from the last four years, the self‐assembly of polymer‐based building blocks, assemblies emerging from small molecules including surfactants or derived from biological macromolecules, and finally the controlled self‐assembly of oligopeptides.

     

Advantages of Catalysis in Self‐Assembled Molecular Capsules

Control over the local chemical environment of a molecule can be achieved by encapsulation in supramolecular host systems. In supramolecular catalysis, this control is used to gain advantages over classical homogeneous catalysis in bulk solution. Two of the main advantages concern influencing reactions in terms of substrate and product selectivity. Due to size and/or shape recognition, substrate selective conversion can be realized. Additionally, noncovalent interactions with the host environment facilitate alternative reaction pathways and can yield unusual products. This Concept article discusses and highlights literature examples utilizing self‐assembled molecular capsules to achieve catalytic transformations displaying a high degree of substrate and/or product selectivity. Furthermore, the advantage of supramolecular hosts in multicatalyst tandem reactions is covered.     

Asymmetric Hydroformylation Using a Rhodium Catalyst Encapsulated in a Chiral Capsule

Supramolecular capsules can be used to change the activity and selectivity of a catalyst through the influence of the second coordination sphere, reminiscent of how enzymes control the selectivity of their processes. In enzymes, this approach is used to also control the enantioselectivity of reactions in which the active catalytic site is often not chiral but the second coordination sphere is. We are interested in the possibility to generate a chiral second coordination sphere around an otherwise achiral transition metal complex for asymmetric catalysis. In this paper we show that the ligand template approach can be used to generate a chiral second coordination sphere around a rhodium complex, which is used in asymmetric hydroformylation.     

Encapsulation of Metalloporphyrins in a Self‐Assembled Cubic M8L6 Cage: A New Molecular Flask for Cobalt–Porphyrin‐Catalysed Radical‐Type Reactions

The synthesis of a new, cubic M₈L₆ cage is described. This new assembly was characterised by using NMR spectroscopy, DOSY, TGA, MS, and molecular modelling techniques. Interestingly, the enlarged cavity size of this new supramolecular assembly allows the selective encapsulation of tetra(4‐pyridyl)metalloporphyrins (M^II(TPyP), M=Zn, Co). The obtained encapsulated cobalt–porphyrin embedded in the cubic zinc–porphyrin assembly is the first example of a catalytically active encapsulated transition‐metal complex in a cubic M₈L₆ cage. The substrate accessibility of this system was demonstrated through radical‐trapping experiments, and its catalytic activity was demonstrated in two different radical‐type transformations. The reactivity of the encapsulated Co^II(TPyP) complex is significantly increased compared to free Co^II(TPyP) and other cobalt–porphyrin complexes. The reactions catalysed by this system are the first examples of cobalt–porphyrin‐catalysed radical‐type transformations involving diazo compounds which occur inside a supramolecular cage.     

Control over Electrochemical Water Oxidation Catalysis by Preorganization of Molecular Ruthenium Catalysts in Self‐Assembled Nanospheres

Oxygen formation through water oxidation catalysis is a key reaction in the context of fuel generation from renewable energies. The number of homogeneous catalysts that catalyze water oxidation at high rate with low overpotential is limited. Ruthenium complexes can be particularly active, especially if they facilitate a dinuclear pathway for oxygen bond formation step. A supramolecular encapsulation strategy is reported that involves preorganization of dilute solutions (10^?5 m ) of ruthenium complexes to yield high local catalyst concentrations (up to 0.54 m ). The preorganization strategy enhances the water oxidation rate by two‐orders of magnitude to 125 s^?1, as it facilitates the diffusion‐controlled rate‐limiting dinuclear coupling step. Moreover, it modulates reaction rates, enabling comprehensive elucidation of electrocatalytic reaction mechanisms.     

Stimuli‐Responsive Cycloaurated “OFF‐ON” Switchable Anion Transporters

Anion transporters have shown potential application as anti‐cancer agents that function by disrupting homeostasis and triggering cell death. In this research article we report switchable anion transport by gold complexes of anion transporters that are “switched on” in situ in the presence of the reducing agent GSH by decomplexation of gold. GSH is found in higher concentrations in tumors than in healthy tissue and hence this approach offers a strategy to target these systems to tumors.     

A Stimuli‐Responsive Rotaxane–Gold Catalyst: Regulation of Activity and Diastereoselectivity

A rotaxane‐based Au catalyst was developed and the effect of the mechanical bond on its behavior was studied. Unlike the non‐interlocked thread, the rotaxane requires a catalytically innocent cofactor, the identity of which significantly influences both the yield and diastereoselectivity of the reaction. Under optimized conditions, Au^I (the catalyst), Ag^I (to abstract the Cl^? ligand), and Cu^I (the cofactor) combine to produce a catalyst with excellent activity and selectivity.     

Biomimetic Strain‐Stiffening Self‐Assembled Hydrogels

Supramolecular structures with strain‐stiffening properties are ubiquitous in nature but remain rare in the lab. Herein, we report on strain‐stiffening supramolecular hydrogels that are entirely produced through the self‐assembly of synthetic molecular gelators. The involved gelators self‐assemble into semi‐flexible fibers, which thereby crosslink into hydrogels. Interestingly, these hydrogels are capable of stiffening in response to applied stress, resembling biological intermediate filaments system. Furthermore, strain‐stiffening hydrogel networks embedded with liposomes are constructed through orthogonal self‐assembly of gelators and phospholipids, mimicking biological tissues in both architecture and mechanical properties. This work furthers the development of biomimetic soft materials with mechanical responsiveness and presents potentially enticing applications in diverse fields, such as tissue engineering, artificial life, and strain sensors.     

Nanostructured Micelle Nanotubes Self‐Assembled from Dinucleobase Monomers in Water

Despite the central importance of aqueous amphiphile assemblies in science and industry, the size and shape of these nano‐objects is often difficult to control with accuracy owing to the non‐directional nature of the hydrophobic interactions that sustain them. Here, using a bioinspired strategy that consists of programming an amphiphile with shielded directional Watson–Crick hydrogen‐bonding functions, its self‐assembly in water was guided toward a novel family of chiral micelle nanotubes with partially filled lipophilic pores of about 2 nm in diameter. Moreover, these tailored nanotubes are successfully demonstrated to extract and host molecules that are complementary in size and chemical affinity.     

Carboxylated Pillar[5]arene‐Coated Gold Nanoparticles with Chemical Stability and Enzyme‐like Activity

A facile synthesis of gold nanoparticles (AuNPs) covered with a multidentate macrocycle, carboxylated pillar[5]arene ( CP ), via a one‐pot hydrothermal process is reported. The resulting AuNPs are highly stable against salts and pH variations, while their traditional counterparts are not stable at the same conditions. For the stabilization, multiple carboxylate groups of CP might contribute to electrostatic or steric stabilization. In addition, we found that CP ‐coated AuNPs exhibit greater peroxidase‐like activity than citrate‐stabilized AuNPs in the presence of silver cations. The system presented herein would provide a new scheme to fabricate unique sensory systems in combination with enzymes, which can bind to the pocket of CP .     

Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self‐Sorting and Self‐Assembly

Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen‐bond‐based self‐assembly. The dynamic character of the linkers and the preference of the peptides towards self‐assembly into β‐barrel‐type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 ų and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self‐sorting and chiral self‐assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C₆₀ or C₇₀, is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C₇₀, and the X‐ray structures provide unique information on the modes of peptide–fullerene interactions.     

Size‐Selective Encapsulation of Hydrophobic Guests by Self‐Assembled M4L6 Cobalt and Nickel Cages

Subtle differences in metal–ligand bond lengths between a series of [M₄L₆]^4? tetrahedral cages, where M=Fe^II, Co^II, or Ni^II, were observed to result in substantial differences in affinity for hydrophobic guests in water. Changing the metal ion from iron(II) to cobalt(II) or nickel(II) increases the size of the interior cavity of the cage and allows encapsulation of larger guest molecules. NMR spectroscopy was used to study the recognition properties of the iron(II) and cobalt(II) cages towards small hydrophobic guests in water, and single‐crystal X‐ray diffraction was used to study the solid‐state complexes of the iron(II) and nickel(II) cages.     

Light‐Controlled Interconversion between a Self‐Assembled Triangle and a Rhombicuboctahedral Sphere

Stimuli‐responsive structural reorganizations play an important role in biological processes, often in combination with kinetic control scenarios. In supramolecular mimics of such systems, light has been established as the perfect external trigger. Here, we report on the light‐driven structural rearrangement of a small, self‐assembled Pd₃L₆ ring based on photochromic dithienylethene (DTE) ligands into a rhombicuboctahedral Pd₂₄L₄₈ sphere measuring about 6.4 nm across. When the wavelength is changed, this interconversion can be fully reversed, as confirmed by NMR and UV/Vis spectroscopy as well as mass spectrometry. The sphere was visualized by AFM, TEM, and GISAXS measurements. Due to dissimilarities in the photoswitch conformations, the interconversion rates between the two assemblies are drastically different in the two directions.     

Orthogonally Self‐Assembled Multifunctional Block Copolymers

We report the synthesis of telechelic poly(norbornene) and poly(cyclooctene) homopolymers by ring‐opening metathesis polymerization (ROMP) and their subsequent functionalization and block copolymer formation based on noncovalent interactions. Whereas all the poly(norbornene)s contain either a metal complex or a hydrogen‐bonding moiety along the polymer side‐chains, together with a single hydrogen‐bonding‐based molecular recognition moiety at one terminal end of the polymer chain. These homopolymers allow for the formation of side‐chain‐functionalized AB and ABA block copolymers through self‐assembly. The orthogonal natures of all side‐ and main‐chain self‐assembly events were demonstrated by ¹H NMR spectroscopy and isothermal titration calorimetry. The resulting fully functionalized block copolymers are the first copolymers combining both side‐ and main‐chain self‐assembly, thereby providing a high degree of control over copolymer functionalization and architecture and bringing synthetic materials one step closer to the dynamic self‐assembly structures found in nature.     

Nanoporous Network Channels from Self‐Assembled Triblock Copolymer Supramolecules

Supramolecular complexes of a poly(tert‐butoxystyrene)‐block‐polystyrene‐block‐poly(4‐vinylpyridine) triblock copolymers and less than stoichiometric amounts of pentadecylphenol (PDP) are shown to self‐assemble into a core–shell gyroid morphology with the core channels formed by the hydrogen‐bonded P4VP(PDP)complexes. After structure formation, PDP was removed using a simple washing procedure, resulting in well‐ordered nanoporous films that were used as templates for nickel plating.

     

Size‐ and Orientation‐Selective Encapsulation of C70 by Cycloparaphenylenes

The size‐ and orientation‐selective formation of the shortest‐possible C₇₀ peapod in solution and in the solid state by using the shortest structural unit of an “armchair” carbon nanotube (CNT), cycloparaphenylene (CPP), has been studied. [10]CPP and [11]CPP exothermically formed 1:1 complexes with C₇₀, thereby giving the resulting peapods. A van′t Hoff plot analysis revealed that the formation of these complexes in 1,2‐dichlorobenzene was mainly driven by entropy, whereas the theoretical calculations suggested that the formation of the complex in the gas phase was predominantly driven by enthalpy. C₇₀ was found to exist in two distinct orientations inside the CPP cavity, namely “lying” and “standing”, depending on the specific size of the CPP. The theoretical calculations and the X‐ray crystallographic analysis revealed that the interactions between [10]CPP and the short axis of C₇₀ in its lying orientation were isotropic and similar to those observed between [10]CPP and C₆₀. However, the interactions between [11]CPP and C₇₀ in its standing orientation were anisotropic, thereby involving the radial deformation of [11]CPP into an ellipsoidal shape. This “induced fit” maximized the van der Waals interactions with the long axis of C₇₀. Theoretical calculations revealed that the deformation occurred readily with low energy loss, thus suggesting that CPPs are highly radially elastic molecules. These results also indicate that the same type of radial deformation should occur in CNT peapods that encapsulate anisotropic fullerenes.