Supramolecular Monomers Research Articles

Supramolecular Assembly of Peptide Amphiphiles.

ConspectusPeptide amphiphiles (PAs) are small molecules that contain hydrophobic components covalently conjugated to peptides. In this Account, we describe recent advances involving PAs that consist of a short peptide sequence linked to an aliphatic tail. The peptide sequence can be designed to form β-sheets among the amino acids near the alkyl tail, while the residues farthest from the tail are charged to promote solubility and in some cases contain a bioactive sequence. In water, β-sheet formation and hydrophobic collapse of the aliphatic tails induce assembly of the molecules into supramolecular one-dimensional nanostructures, commonly high-aspect-ratio cylindrical or ribbonlike nanofibers. These nanostructures hold significant promise for biomedical functions due to their ability to display a high density of biological signals on their surface for targeting or to activate pathways, as well as for biocompatibility and biodegradable nature.Recent studies have shown that supramolecular systems, such as PAs, often become kinetically trapped in local minima along their self-assembly reaction coordinate, not unlike the pathways associated with protein folding. Furthermore, the assembly pathway can influence the shape, internal structure, and dimension of nanostructures and thereby affect their bioactivity. We discuss methods to map the energy landscape of a PA structure as a function of thermal energy and ionic strength and vary these parameters to convert between kinetically trapped and thermodynamically favorable states. We also demonstrate that the pathway-dependent morphology of the PA assembly can determine biological cell adhesion and survival rates.The dynamics associated with the nanostructures are also critical to their function, and techniques are now available to probe the internal dynamics of these nanostructures. For example, by conjugating radical electron spin labels to PAs, electron paramagnetic resonance spectroscopy can be used to study the rotational diffusion rates within the fiber, showing a liquidlike to solidlike transition through the cross section of the nanofiber. PAs can also be labeled with fluorescent dyes, allowing the use of super-resolution microscopy techniques to study the molecular exchange dynamics between PA fibers. For a weak hydrogen-bonding PA, individual PA molecules or clusters exchange between fibers in time scales as short as minutes. The amount of hydrogen bonding within PAs that dictates the dynamics also plays an important role in biological function. In one case, weak hydrogen bonding within a PA resulted in cell death through disruption of lipid membranes, while in another example reduced hydrogen bonding enhanced growth factor signaling by increasing lipid raft mobility.PAs are a promising platform for designing advanced hybrid materials. We discuss a covalent polymer with a rigid aromatic imine backbone and alkylated peptide side chains that simultaneously polymerizes and interacts with a supramolecular PA structure with identical chemistry to that of the side chains. The covalent polymerization can be “catalyzed” by noncovalent polymerization of supramolecular monomers, taking advantage of the dynamic nature of supramolecular assemblies. These novel hybrid structures have potential in self-repairing materials and as reusable scaffolds for delivery of drugs or other chemicals. Finally, we highlight recent biomedical applications of PAs and related structures, ranging from bone regeneration to decreasing blood loss during internal bleeding.

Fluorescent metallacycle-cored polymers via covalent linkage and their use as contrast agents for cell imaging

The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions used to link the monomers are crucial because such monomers are normally dynamic and can disassemble during the linking process, leading to mixture of products. Therefore, although noncovalent interactions have been widely introduced into metallacycle structures to prepare metallosupramolecular polymers, metallacycle-cored polymers linked by covalent bonds have been rarely reported. Herein, we used the mild, highly efficient amidation reaction between alkylamine and N-hydroxysuccinimide-activated carboxylic acid to link the pendent amino functional groups of a rhomboidal metallacycle 10 to give metallacycle-cored polymers P1 and P2, which further yielded nanoparticles at low concentration and transformed into network structures as the concentration increased. Moreover, these polymers exhibited enhanced emission and showed better quantum yields than metallacycle 10 in methanol and methanol/water (1/9, vol/vol) due to the aggregation-induced emission properties of a tetraphenylethene-based pyridyl donor, which serves as a precursor for metallacycle 10. The fluorescence properties of these polymers were further used in cell imaging, and they showed a significant enrichment in lung cells after i.v. injection. Considering the anticancer activity of rhomboidal Pt(II) metallacycles, this type of fluorescent metallacycle-cored polymers can have potential applications toward lung cancer treatment.

Quasi-Block Copolymers Based on a General Polymeric Chain Stopper.

Quasi-block copolymers (q-BCPs) are block copolymers consisting of conventional and supramolecular blocks, in which the conventional block is end-terminated by a functionality that interacts with the supramolecular monomer (a "chain stopper" functionality). A new design of q-BCPs based on a general polymeric chain stopper, which consists of polystyrene end-terminated with a sulfonate group (PS-SO3 Li), is described. Through viscosity measurements and a detailed diffusion-ordered NMR spectroscopy study, it is shown that PS-SO3 Li can effectively cap two types of model supramolecular monomers to form q-BCPs in solution. Furthermore, differential scanning calorimetry data and structural characterization of thin films by scanning force microscopy suggests the existence of the q-BCP architecture in the melt. The new design considerably simplifies the synthesis of polymeric chain stoppers; thus promoting the utilization of q-BCPs as smart, nanostructured materials.

Preparation of Stable Anisotropic Films with Columnar Order from Polymerizable Star-shaped Supramolecular Liquid Crystals

We have fabricated new stable anisotropic films with columnar order using star-shaped supramolecular liquid crystals as photoreactive monomers. The polymerizable supramolecular liquid crystal exhibiting a hexagonal columnar mesophase has been prepared simply through hydrogen bonding between a phloroglucinol core and pyridine derivatives containing acrylate groups in the alkyl chain. Photopolymerization of the supramolecular monomer in the liquid crystalline state yielded cross-linked anisotropic polymer networks with columnar order. The controlled approach in the present study opens a new way to design and prepare stable anisotropic materials for potential electronic and optical applications.

Inclusion induced second harmonic generation in low dimensional supramolecular crystals

A host–guest inclusion complexation self-assembly strategy was developed for the synthesis of SHG-active low dimensional supramolecular crystals (LDSCs). p-Nitroaniline guest molecules with high inherent second-order polarizability were introduced into the cavities of the β-cyclodextrin host to form supramolecular inclusion complexes, which were then assembled into microscale crystalline structures with an anti-solvent diffusion combined solvent-evaporation-induced self-assembly method. Two distinct types of LDSCs with controllable dimensions were obtained by altering the polarity of anti-solvents and the concentration of supramolecular monomers. Each type of LDSCs exhibited its characteristic SHG response to the polarized incident signals, which is attributed to the inherent crystal structures.

Highly Controllable Ring–Chain Equilibrium in Quadruply Hydrogen Bonded Supramolecular Polymers

Electron-rich dioxynaphthalene (DNP) group bridged bifunctional ureidopyrimidinone (UPy) derivatives (L1, L2, and L3) were synthesized, which could form small cyclic monomers, oligomers, or linear supramolecular polymers at certain concentration in solution, to achieve a highly controllable ring–chain equilibrium self-assembling supramolecular system. The ring–chain equilibrium of these supramolecular monomers constructed by different lengths of oligo(ethylene oxide) (oligoEO) chain as spacers were investigated by a combination of techniques, such as 1H NMR, DOSY, single-crystal X-ray diffraction, and viscometry. The experiment results demonstrated that there exists intramolecular π–π stacking interaction between DNP group and intramolecularly dimerized UPy motif in the monomeric cyclic form of these supramolecular monomers, and the strength of this π–π stacking interaction directly depends on the length of the oligoEO chain. Furthermore, strong intramolecular π–π stacking interaction was found to promote self-assembly favorable for intramolecularly cyclic monomerization, leading to a great increase of critical polymerization concentration (CPC). Monomer L1a with the shortest length of oligoEO chain is present as an exclusive type of intramolecularly hydrogen-bonded assembly, namely the cyclic monomers, over a broad concentration range (1.6–500 mM) in solution. Single crystal structure of the cyclic monomer L1b, which is an analogue of L1a, was thoroughly studied. The CPC values of monomer L2 and L3 with longer oligoEO chain are ca. 70 and 23 mM, respectively. However, L2 and L3 could perform selective cyclization over the entire concentration range in solution after threading into the tetracationic cyclobis(paraquat-p-phenylene)cyclophane (CBPQT4+) driven by host–guest interaction, which provides another supramolecular strategy to control ring–chain equilibrium. The combined results may provide new insights into the ring–chain equilibrium and offer valuable information on the understanding of the correlation between supramolecular assistance and polymerizability.

Preparation of conjugated polymeric columns with a hexagonal symmetry from star-shaped supramolecular liquid crystals

New conjugated polymeric columns with a hexagonal symmetry were prepared via topochemical polymerisation of star-shaped supramolecular liquid crystals formed by hydrogen bonding between a phloroglucinol core and pyridine derivatives containing a diacetylenic group in the alkyl chain. The mesomorphic properties of the supramolecular monomer and its photopolymerisation behaviour were investigated. The supramolecular liquid crystal exhibited a rectangular columnar mesophase. Photopolymerisation of supramolecular monomer along the column axis in the liquid crystalline state provided well-ordered conjugated polydiacetylenic columns with a two-dimensional hexagonal symmetry. Fourier transform infrared and ultraviolet–visible spectroscopy affirmed that conjugated polydiacetylenes were produced by 1,4-polymerisation of the supramolecular monomer along the column axis. X-ray diffraction analysis showed that a two-dimensional columnar order in the supramolecular monomer was maintained after photopolymerisation, and that the resulting polydiacetylene had a hexagonal array of conjugated columns. Our controlled methodology provides a new route to conjugated polymeric columns with highly ordered structures by self-assembly and polymerisation of star-shaped supramolecular liquid crystals.

Quasi-Block Copolymers: Design, Synthesis, and Evidence for Their Formation in Solution and in the Melt

A family of block copolymers featuring dynamically controlled compositions is presented. These copolymers, termed “quasi-block copolymers” (q-BCP), consist of a supramolecular polymer as one of the blocks. A conventional polymer end-capped with a functionality that is complementary to the supramolecular monomer is used to terminate the supramolecular block, giving rise to a block copolymer architecture. In this work we have utilized N,N′-2,4-bis((2-ethylhexyl)ureido)toluene (EHUT) as the supramolecular monomer and employed two types of modified 2,4-bis(ureido)toluene polystyrenes as the end-functionalized conventional polymer. Solution viscosity measurements with different solvent compositions and DSC analysis of poly(EHUT)/functionalized-PS blends provide compelling evidence for the formation of self-assembled q-BCP structures both in solution and in the melt. The qualitative role of chain stoppers on the molecular weight distribution is studied by simulations.

One-Pot Synthesis of Polyrotaxanes via Acyclic Diene Metathesis Polymerization of Supramolecular Monomers

A one-pot synthesis of polyrotaxanes has been developed. The method employs a supramolecular monomer comprising a polymerizable ammonium salt and crown ether, in combination with dynamic ADMet polymerization. Ultimately, highly efficient complexation, polymerization, and end-capping were accomplished in a single operation to yield polyrotaxanes with M(w) up to 19.3 kDa and >80% of the repeat units being complexed.

Size-Controlled Fabrication of Supramolecular Vesicles for the Construction of Conjugated Polymer Sensors with Enhanced Optical Properties

Polymerizable supramolecular monomer vesicles are readily fabricated by employing a hydrodynamic focusing method on a microfluidic chip. The polymerized diacetylenene nanovesicles, generated using the microfluidic method, display an improved fluorescence property compared to those prepared by employing a conventional bulk method. The flexibility of the vesicle size control by manipulating the flow conditions is another significant feature of the new microfluidic approach.

Conformational control in the cyclization of hydrogen-bonded supramolecular polymers.

Bifunctional 2-ureido-4[1H]-pyrimidinone (UPy) derivatives can form small cyclic oligomers as well as long supramolecular polymers in chloroform solutions using the quadruple hydrogen-bonding motif. Ring-chain equilibria of a set of supramolecular monomers containing methyl-substituted alkyl linkers between the hydrogen-bonding UPy moieties were investigated by (1)H NMR spectroscopy and viscometry. The data were characterized in terms of critical concentration (CC, denoting the onset of polymerization) and equilibrium cyclic dimer concentration (EDC, representing preorganization of the monomer toward selective formation of cyclic dimer). Methyl substituents in the monomer were found to promote conformations favorable for cyclic dimerization, leading to an increase in both the EDC and the CC with respect to unsubstituted monomer. Furthermore, we observed an odd-even effect in the CC and EDC with increasing length of the linker between the hydrogen-bonding units. The combined results allow tuning of the critical concentration over a broad range and offer detailed information on the correlation between monomer structure, conformation, and polymerizability which may provide new insights for the study and design of other ring-chain equilibria or helix-random coil transitions.