Supramolecular fibers are prominent structures in biology and chemistry. A quantitative understanding of molecular exchange pathways in these one-dimensional aggregates was obtained by a combination of super-resolution stochastic optical reconstruction microscopy and stochastic simulation. The potential of this methodology is demonstrated with a set of well-defined synthetic building blocks that self-assemble into supramolecular fibrils. Previous ensemble measurements hid all molecular phenomena underpinning monomer exchange, but the molecular pathway determined from single-aggregate studies revealed unexpected homogeneous exchange along the polymer backbone. These results pave the way for experimental investigation of the structure and exchange pathways of synthetic and natural supramolecular fibers.

The formation of supramolecular polymers in water through rational design of a benzene-1,3,5-tricarboxamide (BTA) motif is presented. Intermolecular hydrogen bonding and hydrophobic effects cooperate in the self-assembly into long fibrillar aggregates. Minimal changes in molecular structure significantly affect the internal packing of the aggregates.

The rational design of supramolecular polymers in water is imperative for their widespread use, but the design principles for these systems are not well understood. Herein, we employ a multi-scale (spatial and temporal) approach to differentiate two analogous water-soluble supramolecular polymers: one with and one without a stereogenic methyl. Initially aiming simply to understand the molecular behaviour of these systems in water, we find that while the fibres may look identical, the introduction of homochirality imparts a higher level of internal order to the supramolecular polymer. Although this increased order does not seem to affect the basic dimensions of the supramolecular fibres, the equilibrium dynamics of the polymers differ by almost an order of magnitude. This report represents the first observation of a structure/property relationship with regard to equilibrium dynamics in water-soluble supramolecular polymers.

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins have resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA) based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the base of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous ev-idence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the lev-el of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship di-rectly linking the structure of the monomer to the structure and properties of the supramolecular polymer.

Multivalency has an important but poorly understood role in molecular self-organization. We present the noncovalent synthesis of a multicomponent supramolecular polymer in which chemically distinct monomers spontaneously coassemble into a dynamic, functional structure. We show that a multivalent recruiter is able to bind selectively to one subset of monomers (receptors) and trigger their clustering along the self-assembled polymer, behavior that mimics raft formation in cell membranes. This phenomenon is reversible and affords spatiotemporal control over the monomer distribution inside the supramolecular polymer by superselective binding of single-strand DNA to positively charged receptors. Our findings reveal the pivotal role of multivalency in enabling structural order and nonlinear recognition in watersoluble supramolecular polymers, and it offers a design principle for functional, structurally defined supramolecular architectures.self-assembly | simulations | energy transfer O ne of the most fascinating features of living matter is the precise control over biological activity in space and time.The cell membrane provides a remarkable example of such highfidelity spatiotemporal control in a complex biological setting, wherein thousands of different components, namely lipids and proteins, self-assemble into a 2D fluid mosaic (1). To perform the functions that the cell requires, lipids and proteins are heterogeneously distributed and specific biomolecules are segregated in active nanometer-sized domains often referred to as rafts (2). This distribution is highly dynamic, such that these platforms can be rapidly assembled and disassembled (3). The principles that underlie control over the molecular composition of the cellular microenvironment in space and time are the subject of great scientific debate as they are of crucial importance for cell functioning, signaling, growth, and division (4).One of the main goals of supramolecular chemistry is the noncovalent synthesis of functional molecular architectures through weak and reversible interactions (5). In this framework, a key challenge is the design of molecular building blocks that are able to self-organize hierarchically and in a cooperative fashion (6), thus mimicking the dynamic and structural complexity of living systems as well as their functionality. Various modular multicomponent systems have been successfully developed (7), but the spatiotemporal control of the localization of distinct components within synthetic supramolecular assemblies has yet to be realized. Mastering the spatial distribution of assembled molecules in a noncovalent synthesis is as crucial for their functionality as regio-selectivity impacts the molecular properties of organic molecules synthesized in a classical covalent manner. An interesting supramolecular polymer, where multiple components coassemble cooperatively in water, is based on 1,3,5-benzenetricarboxamide derivatives (BTAs) (8).Of particular relevance for the present work, is the fact that reversible interactions between ...

The self-assembly of a family of benzene-1,3,5-tricarboxamides (BTAs) in water is studied systematically to elucidate the role of hydrophobic and hydrogen-bond interactions.

Numerous self-assembling molecules have been synthesized aiming at mimicking both the structural and dynamic properties found in living systems. Here we show the application of hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to unravel the nanoscale organization and the structural dynamics of synthetic supramolecular polymers in water. We select benzene-1,3,5-tricarboxamide (BTA) derivatives that self-assemble in H2O to illustrate the strength of this technique for supramolecular polymers. The BTA structure has six exchangeable hydrogen atoms and we follow their exchange as a function of time after diluting the H2O solution with a 100-fold excess of D2O. The kinetic H/D exchange profiles reveal that these supramolecular polymers in water are dynamically diverse; a notion that has previously not been observed using other techniques. In addition, we report that small changes in the molecular structure can be used to control the dynamics of synthetic supramolecular polymers in water.

Supramolecular 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.