Aurelie M. Brizard

Dissipative Self-Assembly of a Molecular Gelator by Using a Chemical Fuel†

The construction of energy-dissipating self-assembling systems, which, like self-assembled structures found in nature are formed transiently, far from equilibrium, and under the constant influx of chemical energy, still represents a frontier in nanoscale assembly. The self-assembly of small molecules, polymers, proteins, nanoparticles, colloids, and particles with sizes that approach the mesoscale under thermodynamic equilibrium conditions has been a powerful approach for the construction of a variety of structures of nanoto micrometer dimensions, like vesicles, capsules, and nanotubules. The reversible nature of selfassembly processes has been exploited in switchable, adaptive, and autopoietic self-assembling systems, which lead to novel responsive materials and artificial systems that are capable of self-replication and compartmentalization. Recently, there has also been a strongly growing interest in self-assembled materials obtained under non-equilibrium conditions. For instance, the formation of hierarchically structured membranes in a reaction-diffusion field, and the orthogonal self-assembly of molecular gels with surfactants, liquid crystals, or other components can be controlled through the processing conditions, thus leading to a much richer structural diversity compared to equilibriumprocessed materials. These self-assembled structures offer new and intriguing opportunities for functional materials and biomimetic cellular structures. Nevertheless, in all these cases, the final self-assembling systems reside in a (local) thermodynamic minimum state. Despite these advances, the permanent nature of these synthetic self-assembled structures does not compare well to the complex spatiotemporally confined self-assembly processes seen in natural systems, which for instance allow the dynamic compartmentalization of incompatible processes, responsiveness, and self-healing. Natural self-assembled structures such as the cytoskeleton and phospholipid membranes are formed by dissipative self-assembly (DSA). In general, DSA systems consist of non-assembling entities which, through activation by an energy source, assemble into ordered structures. Energy dissipation causes deactivation of the building blocks, hence leading to a collapse of the formed structures. A typical example is microtubule assembly that uses guanosine-5’-triphosphate (GTP) as an energy source, which in turn catalyzes the hydrolysis of GTP and therefore its own collapse. The microtubule assembly process is controlled by feedback loops that lead to self-organization, including oscillatory behavior and nonlinear responses of microtubule formation, which are essential for rapid morphogenic alterations, self-healing, and self-replication. These fascinating properties of natural DSA systems have motivated research on their artificial counterparts. Several artificial DSA systems based on natural building blocks have been reported. Examples of fully artificial DSA systems are most commonly found in the top-down engineered mesoscopic regime with hard inorganic or polymeric objects. The few examples that concern soft matter are mostly fueled by light, whereas the dissipation of “chemical fuels” has been used to drive mechanical motion. It remains a challenge to develop a DSA system that is chemically fueled. A first step towards the development of a self-organizing self-assembly system is the construction of a simple DSA system without feedback control loops. Such a simple system typically follows a sequence of processes. Firstly, an energy source activates the precursor building blocks so that selfassembly is favored. Upon self-assembly, the activated building block can dissipate its energy, thus resulting in the formation of the initial building block and disassembly of the architecture. A requirement is that the rate of energy dissipation (Pd) should be lower than the consumption of fuel (Pc) to allow the formation of self-assembled architectures (Figure 1). Herein we present a synthetic DSA fibrous network that uses chemical fuel as an energy source. A gelator precursor is converted into a gelator by reaction with a chemical fuel, thus leading to self-assembly. Hydrolysis of the gelator, which is labile under ambient conditions, leads to energy dissipation and disassembly of the formed structures. Reactive gels have been previously reported and the hydrolysis of ester functions has been exploited to achieve an enzymatically controlled gel–sol phase transition. The design of the dissipative self-assembling system presented here is based on dibenzoyl-(l)-cystine (DBC; Bz = benzoyl), a well-known pH-responsive hydrogelator . Above their pKa value (ca. 4.5), intermolecular repulsion occurs between the anionic carboxylic acid groups of DBC, and therefore DBC [*] J. Boekhoven, Dr. A. M. Brizard, K. N. K. Kowlgi, Dr. G. J. M. Koper, Dr. R. Eelkema, Prof. Dr. J. H. van Esch Department of Chemical Engineering Delft University of Technology Julianalaan 136, 2628 BL, Delft (The Netherlands) Fax: (+ 31)15-278-4289 E-mail: j.h.vanesch@tudelft.nl Homepage: http://www.dct.tudelft.nl/sas

Self-assembly approaches for the construction of cell architecture mimics

Despite impressive advances in chemistry and biology, the mimicking of the complexity and functionality of natural cells in artificial systems still remains in its infancy. Liposomes for instance have been extensively used to reproduce some basic properties of cells and particularly biological membranes, whereas other studies have focused on the elaboration of fibrous networks to represent intra- and extra cellular matrices. But so far, there are only a few examples in which both cytoskeleton and membranes have been combined. Here we discuss the different strategies towards cell construction mimics explored so far, which consist of the incorporation of artificial fibrillar networks within liposomes. These fibrillar networks can be based on polymers or self-assembled structures, and the examples illustrate how their confinement within artificial cells can affect their shape, stability or compartmentalization. The challenge for the next decades will be to develop systems capable of more complex functions like endo- and exocytosis and motility by including some of the dynamic properties of the natural cytoskeleton.

Programmed Morphological Transitions of Multisegment Assemblies by Molecular Chaperone Analogues

Supramolecular morphological transitions are of great importance in many processes in molecular biology. The Golgi apparatus bilayer, for instance, constantly transforms into cargo vesicles mediated by coaggregation with protein coats, but also proteins fold and unfold by coaggregation with chaperone proteins. In the latter case, chaperones selectively switch off the self-assembly of parts of the protein, thereby controlling their structure and function. Such a strategy can be of use for the development of smart materials, in which an external trigger induces a morphological transition, altering the macroscopic properties of the material. The use of coaggregation to induce morphological transitions has indeed been applied successfully to artificial systems, hence leading to the development of smart materials. The main strategy so far is to alter the packing parameter of a surfactant leading to morphological changes following the structure–shape concept. By this strategy, the transition of vesicles to hexagonal phases by the addition of trimethylbenzene, the conversions of spheres into rods into tubes by addition of ions as well as other additives have been induced. Other strategies to induce morphological changes have also been applied, for example, the use of twocomponent gel systems or photoisomerization of the building block. Although in all cases the mechanisms of these morphological transitions are well understood, the outcome can be hard to predict. Therefore, it remains a challenge to program the outcome of such transitions within the initial building block, which is necessary to use this approach for smart materials. Herein we demonstrate that morphological transitions can easily be programmed by separately addressing the complex aggregation behavior of a segmented self-assembling molecule, using small molecule chaperone analogues, that is, small molecules that selectively switch off self-assembly of another molecule through selective association. As a model system, we use a previously described multisegment amphiphile that consists of two covalently linked but orthogonally self-assembling building blocks, and which forms architectures characterized by each individual segment. Through the addition of a chaperone analogue we can selectively switch off the self-assembly of each of these segments individually, resulting in architectures of the other segment. Interestingly, not only the morphologies of the other segment are retained, but also its dynamics of self-assembly. By such an approach it is possible to design the morphological transitions within the multisegment amphiphile. The multisegment amphiphile (MA 3) is constructed of a gelator segment reminiscent of gelator 1 and a surfactant segment reminiscent of EO4C8 (surfactant 2), which assemble orthogonally (Figure 1a). We have previously shown that MA 3 in water assembles into architectures that display properties of both parental segments. The gelator segment

Introduction of Curvature in Amphipathic Oligothiophenes for Defined Aggregate Formation

In this study the possibility to control the size and shape of self-assembled structures through the local curvature of their molecular building blocks has been investigated. To this end a series of amphipathic conjugated oligothiophenes with a well-defined curvature of their backbone has been designed and synthesized. The molecular (local) curvature of these oligothiophenes resulted from a preference for cis instead of trans conformations at specific positions along the oligothiophene backbone, which can be controlled by the sequence of hydrophilic and hydrophobic groups, while their ratio was kept constant. The self-assembly of ter-, sexi-, and dodecathiophenes appeared to be a low-cooperative process, involving the formation of premicellar aggregates at sub-millimolar concentrations, which at concentrations in the millimolar regime transformed into micelles and cylindrical micelles. The aggregates display fine structures with dimensions reminiscent of the thiophene molecules. The structure-morphology relationship of the ter- and sexithiophenes could be described by conventional packing theory. However, with the dodecathiophene, the backbone curvature governed the formation of cylindrical aggregates with a well-defined diameter. These results demonstrate that it is possible to control the aggregation morphology of simple amphipathic oligothiophenes by implementation of an additional structural motif namely, the curvature.

Self-assembly behaviour of conjugated terthiophene surfactants in water

Conjugated self-assembled systems in water are of great interest because of their potential application in biocompatible supramolecular electronics, but so far their supramolecular chemistry remains almost unexplored. Here we present amphiphilic terthiophenes as a general self-assembling platform for the construction of conjugated aggregates, providing access to aggregates with different morphologies without changing the basic molecular design. We explored the design parameters of these amphiphilic terthiophenes in detail, leading to the selection and synthesis of in total 8 new amphiphilic oligothiophenes. Their aggregation behaviour was investigated by absorbance and fluorescence spectroscopy, dynamic light scattering, and cryo-transmission electron microscopy. Critical micelle concentrations as low as 0.01 mM were found and different sized aggregates ranging from several nanometres up to 200 nm. The aggregate morphology could also be tuned by changing the substitution pattern of hydrophilic and hydrophobic moieties, leading to different types of aggregates ranging from globular- and elongated micelles to bilayers. Remarkably, aggregation had only little effect on the electronic and spectroscopic properties of the oligothiophenes, which will be of interest for their application in supramolecular electronics.

Spin-echo small-angle neutron scattering (SESANS) measurements of needle-like crystallites of gelator compounds

From dibenzoyl cystine, a low molecular weight gelator, we have prepared needle shaped crystals at relatively high concentrations. For the first time SESANS measurements are performed on objects with this geometry. From the measurements the average diameter can be seen directly. From a more careful analysis the width distribution is determined. The gel phase itself prepared at lower concentrations did not show any signal, in contrast to what one observes with conventional SANS. This shows the complementarity of SESANS and SANS.

Orthogonal self-assembly of surfactants and hydrogelators: towards new nanostructures

Self-assembly of small molecular components holds great promises as a bottom-up approach for nano-objects, but functionality of the resulting nanostructures can by far not compete with the sophisticated systems provided by nature. Surfactants, for instance, can lead to a great diversity of aggregates and mesophases (micelles, vesicles, cubic phases...), but with a level of complexity and functionality that still remains limited. Just like in nature, to increase the level of complexity in self-assembling systems, a straightforward approach consists in making use of multiple components that can display orthogonal self-assembly -i.e. the independent formation of two supramolecular structures each with their own characteristic within a single system. More precisely, we have associated surfactants with low-molecular weight hydrogelators: these molecules, based on cyclohexyl-tris-amino acid, can also self-assemble in one direction through the establishment of H-bonds, leading to the formation of a fiber network and consequently macroscopic gels. Work on mixing behavior of surfactants and various gelators have shown the independent formation of a fibrillar network with encapsulated spherical micelles, Figure 1. In order to produce even more complex nanostructures, this approach has been extended to worm-like micelles that can lead to viscoelastic gels, due to their entanglement. Interestingly, the formation of interpenetrating networks, with original and tuneable rheological properties, has been evidenced by cryo-TEM [1]. Screening of various gelators with vesicle-forming surfactants also revealed that most combinations display orthogonal self assembly, Figure 1.