Controlling the size, shape and stability of supramolecular polymers in water

For aqueous based supramolecular polymers, the simultaneous control over shape, size and stability is very difficult1. At the same time, the ability to do so is highly important in view of a number of applications in functional soft matter including electronics, biomedical engineering, and sensors. In the past, successful strategies to control the size and shape of supramolecular polymers typically focused on the use of templates2,3, end cappers4 or selective solvent techniques5. Here we disclose a strategy based on self-assembling discotic amphiphiles that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing electrostatic repulsive interactions on the hydrophilic rim and attractive non-covalent forces within the hydrophobic core of the polymerizing building block, we manage to create small and discrete spherical objects6,7. Increasing the salt concentration to screen the charges induces a sphere-to-rod transition. Intriguingly, this transition is expressed in an increase of cooperativity in the temperature-dependent self-assembly mechanism, and more stable aggregates are obtained. For our study we select a benzene-1,3,5-tricarboxamide (BTA) core connected to a hydrophilic metal chelate via a hydrophobic, fluorinated L-phenylalanine based spacer (Scheme 1). The metal chelate selected is a Gd(III)-DTPA complex that contains two overall remaining charges per complex and necessarily two counter ions. The one-dimensional growth of the aggregate is directed by p-p stacking and intermolecular hydrogen bonding. However, the electrostatic, repulsive forces that arise from the charges on the Gd(III)-DTPA complex start limiting the one-dimensional growth of the BTA-based discotic once a certain size is reached. At millimolar concentrations the formed aggregate has a spherical shape and a diameter of around 5 nm as inferred from 1H-NMR spectroscopy, small angle X-ray scattering, and cryogenic transmission electron microscopy (cryo-TEM). The strength of the electrostatic repulsive interactions between molecules can be reduced by increasing the salt concentration of the buffered solutions. This screening of the charges induces a transition from spherical aggregates into elongated rods with a length > 25 nm. Cryo-TEM allows to visualise the changes in shape and size. In addition, CD spectroscopy permits to derive the mechanistic details of the self-assembly processes before and after the addition of salt. Importantly, the cooperativity -a key feature that dictates the physical properties of the produced supramolecular polymers- increases dramatically upon screening the electrostatic interactions. This increase in cooperativity results in a significant increase in the molecular weight of the formed supramolecular polymers in water

Controlling the Growth and Shape of Chiral Supramolecular Polymers in Water

A challenging target in the noncovalent synthesis of nanostructured functional materials is the formation of uniform features that exhibit well-defined properties, e.g., precise control over the aggregate shape, size, and stability. In particular, for aqueous-based one-dimensional supramolecular polymers, this is a daunting task. Here we disclose a strategy based on self-assembling discotic amphiphiles that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing out attractive noncovalent forces within the hydrophobic core of the polymerizing building blocks with electrostatic repulsive interactions on the hydrophilic rim we managed to switch from elongated, rod-like assemblies to small and discrete objects. Intriguingly this rod-to-sphere transition is expressed in a loss of cooperativity in the temperature-dependent self-assembly mechanism. The aggregates were characterized using circular dichroism, UV and 1H-NMR spectroscopy, small angle X-ray scattering, and cryotransmission electron microscopy. In analogy to many systems found in biology, mechanistic details of the self-assembly pathways emphasize the importance of cooperativity as a key feature that dictates the physical properties of the produced supramolecular polymers

Steric constraints induced frustrated growth of supramolecular nanorods in water

\u3cp\u3eA unique example of supramolecular polymerisation in water based on monomers with nanomolar affinities, which yield rod-like materials with extraordinarily high thermodynamic stability, yet of finite length, is reported. A small library of charge-neutral dendritic peptide amphiphiles was prepared, with a branched nonaphenylalanine-based core that was conjugated to hydrophilic dendrons of variable steric demand. Below a critical size of the dendron, the monomers assemble into nanorod-like polymers, whereas for larger dendritic side chains frustrated growth into near isotropic particles is observed. The supramolecular morphologies observed by electron microscopy, X-ray scattering and diffusion NMR spectroscopy studies are in agreement with the mechanistic insights obtained from fitting polymerisation profiles: non-cooperative isodesmic growth leads to degrees of polymerisation that match the experimentally determined nanorod contour lengths of close to 70 nm. The reported designs for aqueous self-assembly into well-defined anisotropic particles has promising potential for biomedical applications and the development of functional supramolecular biomaterials, with emerging evidence that anisotropic shapes in carrier design outperform conventional isotropic materials for targeted imaging and therapy.\u3c/p\u3

Modular synthesis of supramolecular ureidopyrimidinone-peptide conjugates using an oxime ligation strategy

A convenient method to prepare supramolecular bioconjugates in a facile and scalable manner is by a modular approach, whereby self-assembling units and peptides are coupled using oxime chemistry. We here report syntheses of bioactive ureidopyrimidinone-based peptide conjugates, and their resultant self-assembly into fibrous structure

Mechanistic control over morphology : self-assembly of a discotic amphiphile in water

We report on the self-assembly of discotic amphiphiles that contain chelated gadolinium(III) ions and are based on the C-3-symmetrical benzene-1,3,5-tricarboxamide motif. Fluorescence spectroscopy, SAXS and cryo-TEM experiments demonstrate that a bimodal distribution of small and large aggregates is formed in a ratio that is dependent on the ionic strength. The results correlate with the previously reported degree of cooperativity of the polymerization mechanism, which increases with increasing NaCl concentration. Hence, by tuning the electrostatic interactions between the ligands at the periphery we can tune the cooperativity of the self-assembly. This tunability provides a versatile handle to adjust the size and shape of the discotic amphiphiles, which have potential as supramolecular MRI contrast agents

Supramolecular copolymers predominated by alternating order:theory and application

We investigate the copolymerization behavior of a two-component system into quasi-linear self-assemblies under conditions that interspecies binding is favored over identical species binding. The theoretical framework is based on a coarse-grained self-assembled Ising model with nearest neighbor interactions. In Ising language, such conditions correspond to the anti-ferromagnetic case giving rise to copolymers with predominantly alternating configurations. In the strong coupling limit, we show that the maximum fraction of polymerized material and the average length of strictly alternating copolymers depend on the stoichiometric ratio and the activation free energy of the more abundant species. They are substantially reduced when the stoichiometric ratio noticeably differs from unity. Moreover, for stoichiometric ratios close to unity, the copolymerization critical concentration is remarkably lower than the homopolymerization critical concentration of either species. We further analyze the polymerization behavior for a finite and negative coupling constant and characterize the composition of supramolecular copolymers. Our theoretical insights rationalize experimental results of supramolecular polymerization of oppositely charged monomeric species in aqueous solutions

Controlling the cooperativity in the supramolecular polymerization of ionic discotic amphiphiles via electrostatic screening

In a combined experimental and theoretical approach, we investigate the supramolecular polymerization of ionic discotic amphiphiles into nanorods of varying mean length, depending on the temperature and ionic strength of the buffered aqueous solution. Invoking a nucleated supramolecular polymerization model that explicitly deals with the effects of screened Coulomb interactions, we correlate the degree of cooperativity of the supramolecular polymerization with the ionic strength of the solution, as probed by means of circular dichroism spectroscopy. Experiment and theory show that electrostatic interactions between the amphiphiles in the rods make the polymerization less cooperative, implying that the larger the concentration of mobile ions in the solution the larger the cooperativity due to their screening effect. We furthermore extract quantitative information about the effective surface charge densities of the supramolecular nanorods in solution, a parameter that has been particularly difficult to determine experimentally in other related self-assembled systems

From supramolecular polymers to hydrogel materials

\u3cp\u3eSupramolecular hydrogels formed by decorating benzene-1,3,5-tricarboxamide (BTA) units with amphiphilic ethylene glycol-based side chains are presented; careful selection of the substituents of the BTAs allows for the tuning of the self-assembly behaviour and hence the mechanical properties of the resultant hydrogel.\u3c/p\u3

Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibres

The multicomponent co-assembly of discotic amphiphiles provides a modular and versatile approach to prepare RGDS- and PHSRN-peptide functionalised supramolecular nanofibres, bearing pendant paramagnetic Gd(III)-chelates