Signal transduction in living systems enables adaptive and interactive response to external stimuli. These rudimentary primary processes developed by nature are currently absent in synthetic materials. Implementing these processes in materials can have widespread advances in regenerative medicine, diagnostics or nanomachines. Taking inspiration from nature, organocatalytic reactions will be used in the design of new strategies for signal-responsive materials. These systems undergo physical or mechanical changes in response to stimuli triggered chemical transformations, enabling signal-recognition, signal- translation and ultimately leading to pre-programmed material response. In this thesis, small molecules, usually used as organocatalysts, are implemented in materials to develop signal-triggered and autonomous systems for applications such as controlled drug delivery, autonomous actuators or detection platforms...

Supramolecular hydrogels that are formed from low molecular weight gelators are a new class of soft materials which are gaining prominence. Depending on their molecular make up, these soft gel materials are formed based on different triggers, pH being one among them. In order to build applications with pH-triggered supramolecular gelators, it is necessary to understand their structure-property relationships and learn how to predict, control material properties. As explained in chapter 1, this thesis dealt with the above topics via three distinct fronts: Gelation kinetics, predictive modelling and electrochemical patterning....

This thesis reports on the “structure and supramolecular assembly in multi-component organogels”. It guides readers how the aim of this research has been achieved by division of the main question into subgoals in different chapters. This introduction chapter gives a brief overview on the research theme, it is followed by the second chapter extracted from our literature review on “From molecular assembly to gel formation: what is going on behind the scenes of supramolecular gel formation”. This tutorial review discusses three different assembly mechanisms in molecular gels namely: supramolecular polymerization, crystallization, and spinodal decomposition. The second chapter of this thesis is based on the section on the crystallization mechanism from the larger tutorial review paper, since crystallization is found to be the dominant mechanism of gel formation in bisamide systems throughout our research. It provides a general background on molecular gels followed by how crystallization can lead to the order in the gel network. The third chapter elaborates the study of single bisamide gelators in the solid state. It aims at understanding how odd-even spacer length in the chemical structure affects the complementarity of hydrogen bonding which determines the molecular structure and gelator properties. The fourth chapter describes the supramolecular arrangement and rheological properties of single bisamide gels. In the fifth chapter of this thesis, we explain how we developed and validated the DSCN(T) analytical model. This model empowered our research toolkit to quantitatively analyze the experimental data obtained from DSC. This reliable analysis enabled us to understand the phase behavior of bisamide molecules in the solid state (chapter 3), gel state (chapter 4), and binary systems (both solid and gel state in the subsequent chapter). The last chapter (chapter 6) focuses on the ultimate goal of this thesis: to develop design rules to control the supramolecular assembly pattern in the solid and gel state of multi-component systems. In the course of this phase of research, we made an attempt to understand how compound formation/ co-assembly and phase separation/ self-sorting impact the rheological properties of bisamide gels. The summary of this scientific journey is provided at the end of this thesis.

Smart materials are materials that are capable of responding in a programmable and predictive manner. Such materials respond to a broad variety of internal and external triggers and modulate one or more material properties accordingly. Common material responses are controlled release, color changes, morphological changes or changing the mechanical properties of the bulk material. Well known examples of smart materials in our life are chromoactive materials in sunglasses or windows that change color or transparency when subjected to (sun)light, self-healing concrete and plastics or shape memory materials being responsive to heat. Smart materials often reside in a stationary phase, where built-in molecular functionality can respond autonomously to a changing environment. A material’s response can be triggered by many different stimuli having a chemical nature (e.g. pH, salts and metals), biochemical nature (e.g. peptides, nucleic acids, metabolites and polysaccharides) or a physical nature (e.g. temperature, light, magnetic field and pressure). Materials constructed from polymers, particles or gels can be used for applications such as self-healing, sensing, tissue engineering and drug delivery. Smart materials described in this thesis are designed to respond to signaling molecules, UV light, gamma-radiation or mechanical force. In the following subsections these triggers will be discussed in detail.

Generation of grip on soft tissue in the surgical field is most commonly done with forceps that generate friction grip, that is, the translation of normal (pinch) forces into shear forces. Errors made with these surgical grippers are often force-related: applying too low pinch forces results in slipping of the tissue out of the gripper, and too high pinch forces may lead to tissue damage. One possible solution for generating tissue grip that is secure yet gentle is the adhesive grip. In this case, contact between tissue and gripper is maintained by attracting gripper-tissue interactions, and gripping strength does not depend on the applied pinch forces. Inspiration for the design of such a gripper can be derived from the tree frog, an animal that uses adhesive grip to grip on a range of substrates in its habitat. The main aim of this thesis is to translate grip-generating principles used by tree frogs into designs of artificial adhesives that can generate firm yet gentle grip on soft substrates. The designs of the artificial adhesives in this thesis are inspired by two important characteristics of the tree frog’s attachment apparatus: the hierarchical surface pattern on the tree-frog toe-pad and reinforcing fibrillar structures located inside the pad. Specifically, the aim of this thesis is to mimic function rather than form, and focuses on mechanisms underlying the tree-frog attachment apparatus to satisfy two main requirements for strong grip: (1) contact formation and (2) preservation of the formed contact.

The entire research described in this thesis is part of the larger field of Systems Chemistry. This field of chemistry deals with the understanding of the complexity of biology by mimicking biochemical reaction networks with emergent properties attributed to the entire system. In particular, this research focuses on the design of artificial non-equilibrium chemical reaction networks (CRNs) inspired by signal transduction pathways in living organisms. Specific attention is given to catalysis in such networks. For the design of the catalytic CRNs, organocatalysts are considered as the ideal candidates as they are simple, cheap, recyclable and robust compared to enzymes and frequently less toxic catalysts than metals. On top of that, since organocatalysts can operate under mild conditions, it can pave the way for future applications in biological environments.

This thesis describes the experimental development of new dynamic hydrogels based on reversible thiol conjugate additions. Redox-controlled hydrogels and self-healing injectable hydrogels have been achieved by introducing reversible thiol conjugate additions to crosslink polymers, leading to hydrogel formation. The overall objective in this thesis was to develop a new fuel-driven transient polymeric hydrogel formation system. Although this final aim was not entirely met, we developed several important concepts along the way, which are described in Chapters 2-5. Chapter 2 describes a new chemical reaction network for fuel-driven transient formation of covalent S-C bonds, based on redox-controlled conjugate addition and elimination. We found that the formation and breaking of covalent bonds in the reaction cycle can be realized in separate reactions, but side reactions hindered the operation in full cycle. If such problems would be solved, this CRN could have potential to be used to form fuel-driven polymer materials. Chapter 3 investigates the formation of a self-healing injectable hydrogel by introducing dynamic thiol-alkynone double addition crosslinks in a polymer network. Such dynamic hydrogels show self-healing and shear thinning properties, confirmed by rheological measurements, macroscopic self-healing, and injection tests. Good cytocompatibility of these hydrogels opens an opportunity for future biomedical applications such as tissue engineering and drug delivery. Chapter 4 describes a redox-controlled reversible thiol-alkynone double addition. First, we created a redox-responsive hydrogel by using such reversible addition for the formation of crosslinks in hydrogels. Second, based on this thiol-alkynone double addition, we developed a fuel-driven transient formation of thiol-alkynone double adduct on small molecules. Chapter 5 explores coupling and decoupling reactions of thiols to an azanorbornadiene bromo sulfone. A self-healing hydrogel can be formed by using azanorbornadiene bromo sulfone to couple two thiol groups together. Such hydrogels are also degradable, trigged by glutathione. Glutathione-triggered dye release experiments suggest this self-healing hydrogel is a potential carrier of drugs, cells or vaccines for biomedical applications.

Growing importance of hydrogels in various areas of human life has led to increasing need in controlling their properties, which is generally achieved by adjusting hydrogels shape and microstructure. Even though standard microfabrication and microstructuring techniques can be currently applied in hydrogel research, the variety of properties of hydrogel materials makes it difficult to employ any of these techniques universally. Furthermore, to produce hydrogel structures complex enough to mimic biological tissues, several structuring and microfabrication approaches on various length scales would need to be combined. The complexity and diversity of problems associated with such processes raises a whole set of multidisciplinary challenges. This doctoral dissertation explores novel approaches to structuring and fabrication of polymeric and supramolecular hydrogels by combining modern microfabrication techniques with molecular self-assembly and/or exploiting mutual incompatibility of certain hydrophilic polymers.

Nature is capable of constantly adapting some of its assembled structures in response to external and internal signals. For instance, microtubuli grow and shrink upon cell division and cellular transport. Furthermore, actin fibers play a major role in muscle contraction and cell signaling. To achieve these transient functions, such assembled structures operate in an out-of-equilibrium state. Energy input and dissipation enables structure growth and subsequent collapse. Regulating the energy input with fuel concentration and the activity of associated enzymatically catalyzed processes leads to a high level of kinetic control in biological out-of-equilibrium processes....

Molecular self-assembly has been realized as a powerful approach to control the organization of materials from molecular to macroscopic length scale. While for a long time molecular self-assembly has focused on the investigation of systems involving a single component and under thermodynamic equilibrium. In recent years the interests are shifting towards more complex multicomponent and non-equilibrium self-assembly systems, where the richest functions of the resulted supramolecular objects can be harnessed. In this thesis, multicomponent supramolecular self-assembly and directed molecular self-assembly leading to out-of-equilibrium supramolecular systems are investigated, with the aim to construct new soft functional materials.

Cells react to the environment by changing the activity of enzymes. Catalysts, such as enzymes, speed up reaction rates by lowering the activation energy of the reaction. Changing reaction rates by altering enzyme activity is used to temporarily increase the production of, for instance, a hormone or to change the mechanical properties of a cell. Control over enzyme activity is achieved in two different ways: by covalent modifications (e.g. phosphorylation) and by non-covalent interactions (allosteric enzymes). In this thesis we describe how we designed signal-responsive catalysts and used them to introduce signal response in artificial materials. Inspired by nature we developed a covalent and a noncovalent method to design catalysts that can react to signals from their environment. To design covalently protected catalysts we used self-immolative chemistry. A self-immolative molecule contains a signal-labile functional group. When this group reacts with the signal, the molecule fragments and releases a molecule of interest, in our case a catalyst.

Self-assembly of amphiphilic block copolymers in aqueous solution provides a versatile tool to create complex and functional micelles with various nanostructures, such as spherical, cylindrical and bilayer structures. As an important class in these structures, nanofibrillar micelles have attracted growing interest due to their unique properties that can potentially mimic biological analogues. For example, a great number of nanofibrillar structures, such as actin filaments and collagen gels with filamentous structures, were found in nature systems and have greatly motivated researchers to mimic these systems with synthetic materials. Besides, precise spatiotemporal control and integration of these nanofibrillar structures will offer a powerful strategy for construction of new soft devices in the future. Therefore, in this thesis, we explore the ultra-long, stiff and quenched micelles of diblock copolymers and develop a hybrid approach combining self-assembly of block copolymers and micro-fabrication methods to manipulate these micelles for building soft devices.