Precise Macroscopic Supramolecular Assemblies: Strategies and Applications

Macroscopic supramolecular assembly (MSA) is a new concept in supramolecular science with a focus on interfacial assembly of macroscopic building blocks, which has largely extended the applicable materials of supramolecular assembly and provided new solutions to fabricating tissue scaffolds, soft devices, etc. The precision of the assembled structures is of great interest; unlike molecular assemblies, MSA precision is highly dependent on the matching degree of assembled surfaces because of the large interactive area and group number, which result in remarkably increased kinetic possibilities and metastable assemblies. This Concept introduces the principle, history, and development of MSA, elaborates the low-precision challenge in MSA, summarizes the strategies for precise MSA based on the different thermodynamic stability of precise/imprecise structures and control over assembly kinetics, and finally demonstrates the applications of precise MSA structures in advanced manufacture such as tissue scaffolds.     

Precise Macroscopic Supramolecular Assembly by Combining Spontaneous Locomotion Driven by the Marangoni Effect and Molecular Recognition

Macroscopic supramolecular assembly bridges fundamental research on molecular recognition and the potential applications as bulk supramolecular materials. However, challenges remain to realize stable precise assembly, which is significant for further functions. To handle this issue, the Marangoni effect is applied to achieve spontaneous locomotion of macroscopic building blocks to reach interactive distance, thus contributing to formation of ordered structures. By increasing the density of the building blocks, the driving force for assembly transforms from a hydrophobic–hydrophobic interaction to hydrophilic–hydrophilic interaction, which is favorable for introducing hydrophilic coatings with supramolecular interactive groups on matched surfaces, consequently realizing the fabrication of stable precise macroscopic supramolecular assemblies.     

Highly Stereoselective Recognition and Deracemization of Amino Acids by Supramolecular Self‐Assembly

The highly stereoselective supramolecular self‐assembly of α‐amino acids with a chiral aldehyde derived from binol and a chiral guanidine derived from diphenylethylenediamine (dpen) to form the imino acid salt is reported. This system can be used to cleanly convert D ‐amino acids into L ‐amino acids or vice versa at ambient temperature. It can also be used to synthesize α‐deuterated D ‐ or L ‐amino acids. A crystal structure of the ternary complex together with DFT computation provided detailed insight into the origin of the stereoselective recognition of amino acids.     

Self‐Assembly of Tyrosine into Controlled Supramolecular Nanostructures

In the context of designing novel amino acid nanostructures, the capacity of tyrosine alone to form well‐ordered structures under different conditions was explored. It was observed that Tyr can self‐assemble into well‐defined morphologies when deposited onto surfaces for transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. The influence of various parameters that can modulate the self‐assembly process, including concentration of the amino acid, aging time, and solvent, was studied. Different supramolecular architectures, including nanoribbons, branched structures, and fern‐like arrangements were also observed.     

Boronic Acids in Molecular Self‐Assembly

The reversibility of boronic acid and diol interaction makes it an ideal candidate for the design of self‐assembled molecular structures. Reversibility is required to ensure that the thermodynamically most stable structure is formed. Reversibility also ensures that any errors produced during the assembly process are not permanent.     

Reversible Assembly of Microgels by Metallo‐Supramolecular Chemistry

The combination of supramolecular chemistry and soft colloids as microgels represents an ambitious way to develop multi‐versatile colloidal assemblies. Hereafter, terpyridine‐functionalized poly(N‐isopropylacrylamide) (PNiPAM) microgel building blocks are shown to undergo an assemble–freeze–disassemble process. The microgel assemblies, which are controlled by monitoring the attractive and repulsive potentials between the soft colloidal particles, are then frozen by forming inter‐particle metal–terpyridine bis‐complexes upon addition of the metallic cation (such as Fe^II, Co^II). By oxidation of the metal–terpyridine bis‐complex links, the aggregates open up, which is due to the complex dissociation releasing the connected particles in the form of single microgels. We extended our work to the development of 1D filaments and 2D membranes materials made of soft particles connected via supramolecular chemistry.     

Multicomponent Supramolecular Systems: Self‐Organization in Coordination‐Driven Self‐Assembly

The self‐organization of multicomponent supramolecular systems involving a variety of two‐dimensional (2 D) polygons and three‐dimensional (3 D) cages is presented. Nine self‐organizing systems, SS₁ – SS₉ , have been studied. Each involves the simultaneous mixing of organoplatinum acceptors and pyridyl donors of varying geometry and their selective self‐assembly into three to four specific 2 D (rectangular, triangular, and rhomboid) and/or 3 D (triangular prism and distorted and nondistorted trigonal bipyramidal) supramolecules. The formation of these discrete structures is characterized using NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS). In all cases, the self‐organization process is directed by: 1) the geometric information encoded within the molecular subunits and 2) a thermodynamically driven dynamic self‐correction process. The result is the selective self‐assembly of multiple discrete products from a randomly formed complex. The influence of key experimental variables ‐ temperature and solvent ‐ on the self‐correction process and the fidelity of the resulting self‐organization systems is also described.     

When Self‐Assembly Fails: Stepwise Metal‐Directed Synthesis of [2]Catenanes

On the attempted synthesis of a series of homo‐ and heterotrimetallic [2]catenanes by the self‐assembly of a 2‐(pyridin‐4‐ylmethyl)‐2,7‐diazapyrenium ligand, (ethylenediamine)palladium(II) or platinum(II) nitrate, and a dioxoaryl bis(N‐monoalkyl‐4,4′‐bipyridinium) salt as building blocks, both the one‐pot direct self‐assembly of the components and the so called “magic ring” approach fail to produce the expected trinuclear [2]catenanes under thermodynamically driven conditions. However, one of the target supramolecules is obtained by following a stepwise protocol, consisting of the threading of a dinuclear Pt^II metallacycle and the dioxoaryl bis(N‐monoalkyl‐4,4′‐bipyridinium) axle, followed by kinetically controlled Pt^II‐directed cyclization of the corresponding pseudorotaxane.     

Photo‐Controlled Reversible Microtubule Assembly Mediated by Paclitaxel‐Modified Cyclodextrin

The design and construction of multi‐stimuli‐responsive supramolecular nanoassemblies that can mimic and regulate the fundamental biological processes have become a focus of interest in supramolecular chemistry. In this work, a perfect combination has been achieved between naturally occurring microtubules and artificially macrocyclic receptors. The self‐assembling morphology of microtubules can be photo‐tuned by the host–guest interaction of paclitaxel‐modified β‐cyclodextrin (PTX‐CD) and photochromic arylazopyrazole (PTX‐AAP). Moreover, the supramolecularly aggregated microtubules in a cellular environment can induce a pronounced cell morphological change and cell death. This supramolecular approach based on the secondary PTX‐AAP?PTX‐CD complexation provides us a facile method to reversibly control the intertubular aggregation behaviors of microtubules, which may bring new perspectives in the treatment of diseases related to improper protein aggregation.     

Self‐Assembly Studies of a Chiral Bisurea‐Based Superhydrogelator

A chiral bisurea‐based superhydrogelator that is capable of forming supramolecular hydrogels at concentrations as low as 0.2 mM is reported. This soft material has been characterized by thermal studies, rheology, X‐ray diffraction analysis, transmission electron microscopy (TEM), and by various spectroscopic techniques (electronic and vibrational circular dichroism and by FTIR and Raman spectroscopy). The expression of chirality on the molecular and supramolecular levels has been studied and a clear amplification of its chirality into the achiral analogue has been observed. Furthermore, thermal analysis showed that the hydrogelation of compound 1 has a high response to temperature, which corresponds to an enthalpy‐driven self‐assembly process. These particular thermal characteristics make these materials easy to handle for soft‐application technologies.     

Supramolecular Dendrimers: Convenient Synthesis by Programmed Self‐Assembly and Tunable Thermoresponsivity

We report here the noncovalent synthesis of thermosensitive dendrimers. Short oligoguanosine strands were linked to the focal point of a dendron by using “click chemistry”, and quadruplex formation was used to drive the self‐assembly process in the presence of metal ions. The dynamic nature of these noncovalent assemblies can be exploited to create combinatorial libraries of dendrimers as demonstrated by the co‐assembly of two components. These supramolecular dendrimers showed thermoresponsive behavior that can be tuned by varying the templating cations or the number of guanines in the oligonucleotide strand.     

Self‐Healing Supramolecular Materials Constructed by Copolymerization via Molecular Recognition of Cavitand‐Based Coordination Capsules

The repeating guest units of poly‐(R)‐ 2 were selectively encapsulated by the self‐assembled capsule poly‐ 1 possessing eight polymer side chains to form the supramolecular graft polymer (poly‐ 1 )_n?poly‐(R)‐ 2 . The encapsulation of the guest units was confirmed by ¹H NMR spectroscopy and the DOSY technique. The hydrodynamic radius of the graft polymer structure was greatly increased upon the complexation of poly‐ 1 . The supramolecular graft polymer (poly‐ 1 )_n?poly‐(R)‐ 2 was stably formed in the 1:1 host–guest ratio, which increased the glass transition temperature by more than 10 °C compared to that of poly‐ 1 . AFM visualized that (poly‐ 1 )_n?poly‐(R)‐ 2 formed the networked structure on mica. The (poly‐ 1 )_n?poly‐(R)‐ 2 gelled in 1,1,2,2‐tetrachloroethane, which led to fabrication of distinct viscoelastic materials that demonstrated self‐healing behavior in a tensile test.     

Coordination‐Driven Self‐Assembly of PEO‐Functionalized Perylene Bisimides: Supramolecular Diversity from a Limited Set of Molecular Building Blocks

A limited number of poly(ethylene oxide)‐substituted perylene bisimides, some of which are equipped with terpyridine ligands for transition‐metal coordination (see structure), combine different types of noncovalent interactions to yield optoelectronically active organic materials with different types of supramolecular morphologies.

     

pH‐Responsive Self‐Assembly by Molecular Recognition on a Macroscopic Scale

Macroscopic pH‐responsive self‐assembly is successfully constructed by polyacrylamide(pAAm)‐based gels carrying dansyl (Dns) and β‐cyclodextrin (βCD) residues, which are represented as Dns‐gel and βCD‐gel, respectively. Dns‐gel and βCD‐gel assemble together at pH ≥ 4.0, but disassemble at pH ≤ 3.0. The adhesion strengths for pairs of Dns‐gel/βCD‐gel increase with increasing pH. The fluorescence study on the model system of pAAm modified with 1 mol% Dns moieties (pAAm/Dns) reveals that Dns residues are protonated at a lower pH, which results in the reduction in binding constant (K) for Dns residues and βCD.

     

Inversion of the Supramolecular Chirality of Nanofibrous Structures through Co‐Assembly with Achiral Molecules

To understand the behavior of chiral nanostructures, it is of critical importance to study how achiral molecules regulate the chirality of such nanostructures and what the main driving forces for the regulation processes are. In this work, the supramolecular chirality of helical nanofibers consisting of phenylalanine‐based enantiomers is inverted by achiral bis(pyridinyl) derivatives through co‐assembly. This inversion is mainly mediated by intermolecular hydrogen bonding interactions between the achiral additives and the chiral molecules, which may induce stereoselective interactions and different reorientations for the assembled molecules, as confirmed by calculations. This work not only exemplifies a feasible method to invert the helicity of chiral nanostructures by the addition of achiral molecules, but also provides a method to explore their functions in environments where chiral and achiral molecules are in close proximity.     

Hierarchical Self‐Assembly of Supramolecular Hydrophobic Metallacycles into Ordered Nanostructures

We describe herein the hierarchical self‐assembly of discrete supramolecular metallacycles into ordered fibers or spherical particles through multiple noncovalent interactions. A new series of well‐defined metallacycles decorated with long alkyl chains were obtained through metal–ligand interactions, which were capable of aggregating into ordered fibroid or spherical nanostructures on the surface, mostly driven by hydrophobic interactions. In‐depth studies indicated that the morphology diversity was originated from the structural information encoded in the metallacycles, including the number of alkyl chains and their spatial orientation. Interestingly, the morphology of the metallacycle aggregates could be tuned by changing the solvent polarity. These findings are of special significance since they provide a simple yet highly controllable approach to prepare ordered and tunable nanostructures from small building blocks by means of hierarchical self‐assembly.