Supramolecular Polymerization Process Research Articles

Unveiling the Liquid‐Liquid Phase Separation of Benzene‐1,3,5‐Tricarboxamide in Water

The intricate interplay between self‐assembly and phase separation orchestrates biomolecular organization inside cells, thereby dictating the formation of vital structures such as protein assemblies and membraneless organelles (MLOs). However, in the context of supramolecular polymerization, these fundamental processes have traditionally been studied separately. This study reevaluates the supramolecular polymerization process to unveil the presence of phase‐separated droplet state. Utilizing the well‐studied benzene‐1,3,5‐tricarboxamide (BTA) supramolecular motif, we explore its thermally driven liquid‐liquid phase separation (LLPS). Thermodynamic and kinetic analysis, employing temperature‐dependent spectroscopic and microscopic techniques, elucidates the distinct BTA states and their evolution towards the thermodynamic fiber state. This research sheds light on the existence of hidden phases of supramolecular monomers, emphasizing the delicate balance of non‐covalent interactions among monomers and with solvents in governing self‐assembly vs. phase separation. This is particularly important in comprehending phase separation in the biological realm such as in MLOs, and for applications such as condensate‐modifying therapeutics.

Noncovalent Catalyst-cum-Inhibitor Directed Supramolecular Pathway Selection and Asymmetry Amplification by Aggregate Cross-Nucleation.

The key to any controlled supramolecular polymerization (CSP) process lies in controlling the nucleation step, which is typically achieved by sequestering monomers in a kinetically trapped state. However, kinetic traps that are shallow cannot prevent spontaneous nucleation, thus limiting the applicability of the CSP in such systems. We use a molecular additive to overcome this limitation by modifying the energy landscape of a competitive self-assembly process and increasing the kinetic stability of an otherwise short-lived trap state. The additive achieves this by simultaneously catalyzing OFF-pathway nucleation and inhibiting ON-pathway aggregation. In the process, it guides the molecular assembly exclusively toward the OFF-pathway aggregate analogue. The mechanisms of OFF-pathway catalysis and ON-pathway inhibition are elucidated. By specifically targeting the nucleation step, it was possible to achieve pathway selection at an extremely low additive-to-monomer ratio of 1:100. The generality of our approach is also demonstrated for other related molecular systems. Finally, removing the additive triggers the cross-nucleation of the ON-pathway aggregate on the surface of a less stable, OFF-pathway aggregate analogue. The resultant supramolecular polymer not only exhibits a more uniform morphology but more importantly, a marked improvement in the structural order that leads to an amplification of chiral asymmetry and a high absorption dissymmetry factor (gAbs) of ∼0.05.

Photoswitchable Quadruple Hydrogen-Bonding Motif.

Multiple hydrogen-bonding motifs serve as important building blocks for molecular recognition and self-assembly. Herein, a photoswitchable quadruple hydrogen-bonding motif featuring near-complete, reversible, and thermostable conversion between DADA and AADD arrays associated with an alteration of their dimerization constants by over 3 orders of magnitude is reported. The system is based on a diarylethene featuring a ureidopyrimidin-4-ol moiety, which upon photoinduced ring closure and associated loss of aromaticity undergoes enol-keto tautomerization to a ureidopyrimidinone moiety. The latter causes a transformation of the hydrogen-bonding arrays and significantly weakens the free energy of dimerization in the case of the closed isomer. This photoswitchable quadruple hydrogen-bonding motif should allow us to spatially and temporarily direct self-assembly and supramolecular polymerization processes by light.

Phenazine functionalized pillar[5]arene: Synthesis, host-guest property and application in the fluorescence sensing of biogenic amine in solution, gel and air

The development of selective sensing materials for biogenic amine detection has attracted tremendous interest because amines have high toxicity and exist widely. In this paper, phenazine-bridged pillar[5]arene monomers PA and a naphthalene diimide containing neutral guest-bearing alkyl chain binding sites NDI were designed and synthesized. They could self-assemble by host–guest interactions to form a microsphere structure in dilute solution. A series of biogenic amines can selectively quench the microsphere fluorescence. The microsphere structure transformed into the supramolecular polymer gel at relatively high concentrations. More interestingly, the supramolecular polymerization process induced fluorescence emission enhancement based on an AIE mechanism in the gel state. The supramolecular polymer gel material exhibited sensitive stimulus–response behavior owing to stimuli-induced reversible electron transfer in the presence of various amines. The gel soft material collapse could be achieved by fuming under a series of amines vapors. Besides, our results demonstrate an effective material design strategy that may be extended to fluorescence sensing of biogenic amine in solution, gel, and air and applications to detect food spoilage. It is envisaged that this important method would pave the way for overcoming the sensor's application constraints in the solution state.

Pathway Control of π‐Conjugated Supramolecular Polymers by Incorporating Donor‐Acceptor Functionality

AbstractControlling the nanoscale orientation of π‐conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π‐conjugated supramolecular polymers, by incorporating both electron‐rich methoxy‐ or methanthiol‐benzene as donor unit and electron‐poor cyano‐vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel‐stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip‐stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor‐acceptor packing. By further investigating the external seed‐induced kinetic‐to‐thermodynamic transformation behaviors, our findings suggest that the donor‐acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π‐conjugated nanostructures.

Pathway Control of π-Conjugated Supramolecular Polymers by Incorporating Donor-Acceptor Functionality.

Controlling the nanoscale orientation of π-conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π-conjugated supramolecular polymers, by incorporating both electron-rich methoxy- or methanthiol-benzene as donor unit and electron-poor cyano-vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel-stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip-stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor-acceptor packing. By further investigating the external seed-induced kinetic-to-thermodynamic transformation behaviors, our findings suggest that the donor-acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π-conjugated nanostructures.

Multistep, site-selective noncovalent synthesis of two-dimensional block supramolecular polymers.

Although the principles of noncovalent bonding are well understood and form the basis for the syntheses of many intricate supramolecular structures, supramolecular noncovalent synthesis cannot yet achieve the levels of precision and complexity that are attainable in organic and/or macromolecular covalent synthesis. Here we show the stepwise synthesis of block supramolecular polymers from metal-porphyrin derivatives (in which the metal centre is Zn, Cu or Ni) functionalized with fluorinated alkyl chains. These monomers first undergo a one-dimensional supramolecular polymerization and cyclization process to form a toroidal structure. Subsequently, successive secondary nucleation, elongation and cyclization steps result in two-dimensional assemblies with concentric toroidal morphologies. The site selectivity endowed by the fluorinated chains, reminiscent of regioselectivity in covalent synthesis, enables the precise control of the compositions and sequences of the supramolecular structures, as demonstrated by the synthesis of several triblock supramolecular terpolymers.

Controlling the Supramolecular Polymerization of Squaraine Dyes by a Molecular Chaperone Analogue

Molecular chaperones are proteins that assist in the (un)folding and (dis)assembly of other macromolecular structures toward their biologically functional state in a non-covalent manner. Transferring this concept from nature to artificial self-assembly processes, here, we show a new strategy to control supramolecular polymerization via a chaperone-like two-component system. A new kinetic trapping method was developed that enables efficient retardation of the spontaneous self-assembly of a squaraine dye monomer. The suppression of supramolecular polymerization could be regulated with a cofactor, which precisely initiates self-assembly. The presented system was investigated and characterized by ultraviolet-visible, Fourier transform infrared, and nuclear magnetic resonance spectroscopy, atomic force microscopy, isothermal titration calorimetry, and single-crystal X-ray diffraction. With these results, living supramolecular polymerization and block copolymer fabrication could be realized, demonstrating a new possibility for effective control over supramolecular polymerization processes.

Molecular Engineering of the Kinetic Barrier in Seeded Supramolecular Polymerization.

Seeded supramolecular polymerization (SSP) is a method that enables the controlled synthesis of supramolecular structures. SSP often relies on structures that are capable of self-assembly by interconverting between intramolecular and intermolecular modes of hydrogen bonding, characterized by a given kinetic barrier that is typically low. The control of the polymerization process is thus limited by the propensity of the hydrogen bonds to interconvert between the intramolecular and intermolecular modes of binding. Here, we report on an engineering of the polymerization kinetic barriers by sophisticated molecular design of the building blocks involved in such SSP processes. Our designs include two types of intramolecular hydrogen-bonded rings: on one hand, a central triazine tricarboxamide moiety that prevents self-assembly due to its stable intramolecular hydrogen bonds and on the other hand, three peripheral amide groups that promote self-assembly due to their stable intermolecular hydrogen bonds. We report a series of molecules with increasing bulkiness of the peripheral side chains exhibiting increasing kinetic stability in the monomeric form. Owing to the relative height of the barrier, we were able to observe that the rate constant of seeding is not proportional to the concentration of the seeds used. Based on that, we proposed a new kinetic model in which the rate-determining step is the activation of the monomer, and we provide the detailed energy landscape of the supramolecular polymerization process. Finally, we investigated the hetero-seeding of the building blocks that shows either inhibition or triggering of the polymerization.

Exploiting Hydrogen Bonding to Direct Supramolecular Polymerization at the Air/Water Interface

AbstractFluid interfaces provide an advanced platform for directed self‐assembly of organic composites and formation of supramolecular polymers (SPs). Intermolecular interactions govern the supramolecular polymerization processes, with hydrogen bonding (H‐bonding) as a key interaction in supramolecular chemistry and biology. Two purposefully designed supra‐amphiphiles for assessing the role of H‐bonding were designed and their supramolecular polymerization (SP) at the air/water interface was compared. H‐bonding was confirmed by in situ experimental and computational techniques as the required intermolecular interaction for attaining SPs with well‐defined molecular arrangement. Control of H‐bonding as opposite to traditionally considered interactions (e. g., π‐π stacking) is proposed as a successful strategy for SP at fluid interfaces.

Chiral Self-Recognition and Self-Discrimination Processes in Different Subphthalocyanine Aggregation Regimes

We have recently shown that, as a result of its rigid cone-shaped structure, racemic SubPcs trisubstituted with peripheral amides can self-assemble in two distinct regimes as a function of the solvent environment.1 In toluene, an apolar aromatic medium that can efficiently solvate p-surfaces, such compounds associate as tail-to-tail dimers (regime A). In methylcyclohexane (MCH), in contrast, they undergo a cooperative supramolecular polymerization process to yield non-centrosymmetric head-to-tail columnar stacks (regime B).2 SubPcs, being intrinsically chiral molecule, constitutes an ideal probe to study chiral self-sorting processes, which is the objective of this work. As depicted in the figure below, a racemic mixture of a trisubstituted SubPc can in principle self-assemble into different species. Homochiral dimers/polymers may form through a chiral self-recognition process: each enantiomer has a preference to aggregate with itself leading to helical supramolecular structures with a preferred handedness. At the other extreme, heterochiral dimers/polymers would be instead formed via a chiral self-discrimination process, where each enantiomer prefers to associate with the other, yielding purely racemic dimers/polymers displaying no predilection for a given helical sense. As an intermediate case, the enantiomers might show no strong self-sorting preference and yield statistical dimers/polymers.[1] C. G. Claessens, D. González-Rodríguez, M. S. Rodríguez-Morgade, A. Medina, T. Torres, Chem. Rev. 2014, 114, 2192.[2] (a) J. Calbo, J. Aragó, P. M. Viruela, E. Ortí, T. Torres, D. González-Rodríguez, Angew. Chem. Int. Ed. 2015, 54, 2543; (b) M. J. Mayoral, J. Guilleme, J. Calbo, J. Aragó, F. Aparicio, E. Ortí, T. Torres, D. González-Rodríguez, J. Am. Chem. Soc. 2020 , 142, 21017. Figure 1

In Situ Supramolecular Polymerization via Organometallic-Catalyzed Macromolecular Metamorphosis

In Situ Supramolecular Polymerization via Organometallic-Catalyzed Macromolecular Metamorphosis

Macrocycle-Based Solid-State Supramolecular Polymers.

Supramolecular polymers, generated by connecting monomers through noncovalent interactions, have received considerable attention over the past years, as they provide versatile platforms for developing diverse aesthetically pleasing polymeric structures with promising applications in a variety of fields, such as medicine, catalysis, and sensing. In the development of supramolecular polymers, macrocyclic hosts play a very important role. Benefiting from their abundant host-guest chemistry and self-assembly characteristics, macrocycles themselves or their host-guest complexes can self-assemble to form well-ordered supramolecular polymeric architectures including pseudopolyrotaxanes and polyrotaxanes. The integration of these topological structures into supramolecular polymeric materials also imbues them with some unforeseen functions. Current interest in macrocycle-based supramolecular polymers is mostly focused on the development of supramolecular soft materials in solution or gel-state, in which the dynamic nature of noncovalent interactions endows supramolecular polymers with a wealth of "smart" properties, such as multiresponsiveness and self-repair capabilities. While preparation of macrocycle-derived supramolecular polymers in the solid state is a relatively challenging but intriguing prospect, they are an important part of the field of supramolecular polymers. On one hand, the construction of macrocycle-based solid-state supramolecular polymers enables us to obtain new materials with novel properties and functions such as mechano-responsiveness. On the other hand, the molecular structures and arrangements in these materials are well-identified by X-ray crystallography techniques, offering a direct visual representation of the supramolecular polymerization process. The analysis of the role of noncovalent interactions in these architectures allows us to design more sophisticated and elegant supramolecular polymers in a highly rationalized and controllable manner. This Account serves to summarize the research progress on macrocycle-based solid-state supramolecular polymers (MSSPs), including the contributions toward this field made by our group. For constructing MSSPs, the key point is to control noncovalent interactions. Thus, in this Account, we primarily classify these MSSPs by different noncovalent interactions involved to connect the monomers, including metal-ligand interactions, host-guest interactions, π···π stacking, and halogen bonding. These noncovalent interactions are highly associated with the structures and functions of the resultant MSSPs. For instance, using metal-ligand interactions as driving forces, metal clusters can be introduced in MSSPs which afford systems with solid-state luminescence or proton conduction properties; supramolecular polymerization using macrocycle-based host-guest interactions can modulate the molecular arrangement of some specific molecules in the solid state, which further influences their solid-state properties; π···π stacking interactions and halogen bonding give chemists more choice to design MSSPs with various elements. The role of macrocyclic hosts in MSSPs is also revealed in these descriptions. Finally, the remaining challenges are identified for further development of future prospects. We hope that this Account can inspire new discoveries in the realm of supramolecular functional systems and offer new opportunities for the construction of supramolecular architectures and solid-state materials.

Supramolecular Polymerization Powered by Escherichia coli : Fabricating a Near-Infrared Photothermal Antibacterial Agent in Situ

Supramolecular Polymerization Powered by <i>Escherichia coli</i> : Fabricating a Near-Infrared Photothermal Antibacterial Agent in Situ

Modeling and Designing Particle-Regulated Amyloid-like Assembly of Synthetic Polypeptides in Aqueous Solution.

In cells, actin and tubulin polymerization is regulated by nucleation factors, which promote the nucleation and subsequent growth of protein filaments in a controlled manner. Mimicking this natural mechanism to control the supramolecular polymerization of macromolecular monomers by artificially created nucleation factors remains a largely unmet challenge. Biological nucleation factors act as molecular scaffolds to boost the local concentrations of protein monomers and facilitate the required conformational changes to accelerate the nucleation and subsequent polymerization. An accelerated assembly of synthetic poly(l-glutamic acid) into amyloid fibrils catalyzed by cationic silica nanoparticle clusters (NPCs) as artificial nucleation factors is demonstrated here and modeled as supramolecular polymerization with a surface-induced heterogeneous nucleation pathway. Kinetic studies of fibril growth coupled with mechanistic analysis demonstrate that the artificial nucleators predictably accelerate the supramolecular polymerization process by orders of magnitude (e.g., shortening the assembly time by more than 10 times) when compared to the uncatalyzed reaction, under otherwise identical conditions. Amyloid-like fibrillation was supported by a variety of standard characterization methods. Nucleation followed a Michaelis-Menten-like scheme for the cationic silica NPCs, while the corresponding anionic or neutral nanoparticles had no effect on fibrillation. This approach shows the effectiveness of charge-charge interactions and surface functionalities in facilitating the conformational change of macromolecular monomers and controlling the rates of nucleation for fibril growth. Molecular design approaches like these inspire the development of novel materials via biomimetic supramolecular polymerizations.

Stereoselective Primary and Secondary Nucleation Events in Multicomponent Seeded Supramolecular Polymerization.

Bioinspired, kinetically controlled seeded growth has been recently shown to provide length, dispersity, and sequence control on the primary structure of dynamic supramolecular polymers. However, command over the molecular organization at all hierarchical levels for the modulation of higher order structures of supramolecular polymers remains a formidable task. In this context, a surface-catalyzed secondary nucleation process, which plays an important role in the autocatalytic generation of amyloid fibrils and also during the chiral crystallization of small monomers, offers exciting possibilities for topology control in synthetic macromolecular systems by introducing secondary growth pathways compared to the usual primary nucleation-elongation process. However, mechanistic insights into the molecular determinants and driving forces for the secondary nucleation event in synthetic systems are not yet realized. Herein, we attempt to fill this dearth by showing an unprecedented molecular chirality control on the primary and secondary nucleation events in seed-induced supramolecular polymerization. Comprehensive kinetic experiments using in situ spectroscopic probing of the temporal changes of the monomer organization during the growth process provide a unique study to characterize the primary and secondary nucleation events in a supramolecular polymerization process. Kinetic analyses along with various microscopic studies further reveal the remarkable effect of stereoselective nucleation and seeding events on the (micro)structural aspects of the resulting multicomponent supramolecular polymers.

Supramolecular Polymerization of C3-Symmetric, Triphenylene-Cored Aza-Polycyclic Aromatic Hydrocarbons with Excellent and Switchable Circularly Polarized Luminescence Performance

A new type of C3-symmetric aza-polycyclic aromatic hydrocarbon (PAH) discs attached with chiral alkoxyl chains is developed and explored as circularly polarized luminescence (CPL)-active materials with selective control and switching of chiroptical properties. Supramolecular polymerization of these PAHs is studied experimentally and theoretically. With the aid of weak hydrogen bonding and CH···π interactions, these chromophores have strong tendency to form anisotropic chiral aggregates both in solutions and films. The well-controlled noncovalent interactions are critical for their excellent CPL performance. The resultant supramolecular polymers display a polarized emission band with the maximum glum value up to 10–2. Benefited from the chiral supramolecular polymerization process and N-doping structure feature of the core, on/off CPL switching from these molecules can be reversibly realized by external stimuli including the change of temperature, solvent, and pH conditions. Our work shows that chiral supramolecular polymers from concise yet highly rigid and planar PAH cores are superbly suitable for exceptional CPL emission both in dilute solutions and bulk materials, with a promising switchable CPL feature, thereby unlocking new design possibilities.

Structure and solvent effects on the stability of platinum(II) acetylide-based supramolecular polymers

Stability and stimuli-responsiveness are important parameters for dynamic supramolecular polymers. Herein we have found that, as compared to cyclic alkanes, linear alkanes facilitate to enhancement of solvo-, thermo-stability and photo-resistance for platinum(II) acetylide-based one-dimensional supramolecular polymers. It is primarily ascribed to low steric hindrance for linear alkane solvents, which tend to intercalate into the gap of the peripheral alkyl chains and thereby display higher Gibbs free energy for supramolecular polymerization processes. In addition, supramolecular polymers exhibit high thermo-stability by incorporating higher-order acenes to platinum(II) acetylide core unit, because of their stronger π-π stacking strength. Accordingly, the current study highlights the importance of structure and solvent parameters for the rational design of platinum(II) acetylide-based supramolecular polymers.

Tuning Aqueous Supramolecular Polymerization by an Acid-Responsive Conformational Switch.

Besides their widespread use in coordination chemistry, 2,2’‐bipyridines are known for their ability to undergo cis–trans conformational changes in response to metal ions and acids, which has been primarily investigated at the molecular level. However, the exploitation of such conformational switching in self‐assembly has remained unexplored. In this work, the use of 2,2’‐bipyridines as acid‐responsive conformational switches to tune supramolecular polymerization processes has been demonstrated. To achieve this goal, we have designed a bipyridine‐based linear bolaamphiphile, 1, that forms ordered supramolecular polymers in aqueous media through cooperative aromatic and hydrophobic interactions. Interestingly, addition of acid (TFA) induces the monoprotonation of the 2,2’‐bipyridine moiety, leading to a switch in the molecular conformation from a linear (trans) to a V‐shaped (cis) state. This increase in molecular distortion along with electrostatic repulsions of the positively charged bipyridine‐H+ units attenuate the aggregation tendency and induce a transformation from long fibers to shorter thinner fibers. Our findings may contribute to opening up new directions in molecular switches and stimuli‐responsive supramolecular materials.

Light‐Fuelled Self‐Assembly of Cyclic Peptides into Supramolecular Tubules

AbstractThe work performed by supramolecular polymers, such as microtubules and actin filaments, supports the life of the cell, and essentially involves fuel‐driven self‐assembly pathways. Developing fuel‐driven supramolecular polymerization processes is therefore crucial to the realization of mechanically active molecular systems. Here, we demonstrate supramolecular tubules with non‐equilibrium steady states that are fuelled by light. This dynamic supramolecular system features rapid cycles of self‐assembly and disassembly, at rates that appear fast enough to perform mechanical tasks in fluids effectively.