Engineering new supramolecular gels: From catalysis to drug delivery

The present dissertation evaluates the design, characterization and potential applications of functional supramolecular gel-materials. Gels have attracted tremendous scientific interest as they can be obtained from natural sources or derive from readily available building blocks by facile preparation methods. They have conquered our daily life appearing as constituents of commercial products in the fields of biomedicine, agriculture, cosmetics, food thickeners and many more. Gel-materials exhibit a continuous structure and embody a meta-stable state between liquids and solids. They can be categorized by physical and chemical gels, depending on the forces responsible for their formation. Physical or supramolecular gels are solely held together by weak and non-covalent forces, which provides a potential response to external stimuli and hence they represent the main focus of research conducted in this thesis. In this context, the present work has been divided into three main parts: Introduction, Main part and Supporting Information enclosed on a CD. The first part of the introduction provides a broader overview on natural and artificial self-assembling systems in order to demonstrate nature´s power of generating well-ordered complex structures with controlled function from available building blocks without human intervention and how we can take lessons for the fabrication of novel materials and devices. A general definition and classification of gels is given in the second part of the introduction in order to get a detailed insight into the diversity of gel-subclasses and to understand the forces necessary to promote the mechanisms of self-assembling gel-formation. The last part of the introduction focuses on high-tech applications of gel-materials in the fields of biomedicine, catalysis and fabrication of nanoparticles of well-defined shape and size. Herein the center of interest lies in the evaluation of potential advantages of 3D gel-environments for applications against already established materials and procedures. Chapter 1 describes the design and evaluation of gelation properties of novel peptide-based organogelators with side-chain azobenzene modifications. In this context, effective gelation of various organic solvents could be observed at relatively low concentrations without a major effect of the position of the azobenzene-moieties inside the gelator-structure. The presence of azobenzene-functionalities was found to exhibit a positive effect on the gelation properties by lowering minimum gelation concentrations and improving thermal and mechanical stabilities in comparison to control-peptides. Furthermore, photo-induced gel-to-sol transition could be achieved by UV-irradiation of gel-samples due to a rapid trans-to-cis isomerization reaction (30-60 min) of the azobenzenes, which was found to be reversible when the samples were left for relaxation. Interestingly, light-driven phase transition was only feasible for peptide-gelators lacking N-terminal protecting groups. It is important to mention, that such stimuli-responsive behavior is a key concept for the fabrication of functional materials for biomedical and optoelectronic applications. Additionally, we were delighted to observe a phase selective gelation behavior of our gelators, which could be induced by room temperature gelation protocols for potential application in oil-spill recovery and dye-removal. Chapter 2 focuses on the exploration of various supramolecular gel-scaffolds as reaction vessels in photo-chemical transformations. Due to the growing demand for sustainability in industrial applications, photochemistry provides efficient and clean alternatives towards conventional processes. Inspired by nature, we investigated the photo-oxidation of a secondary benzyl-alcohol catalyzed by flavin-derivatives in a library of diverse gel-based matrices. Gel-materials provide a well-structured highly porous network and are literally predestinated to serve as nanoreactors, in which alternative selectivities or reaction pathways could be accessible. In this context, we were able to demonstrate that the structure-property relationship of gels derived from both (bio-)polymers and low molecular weight compounds has a direct influence on the kinetics and outcome of the model-reaction. Although it is known that photo-chemical transformation progress less efficient in organic solvents such as acetonitrile, an organogelator proved to be most active to promote the photo-oxidation reactions. Due to the confined gel-network, reaction rates were found to be slightly reduced in comparison to aqueous and micellar environments under non-stirred conditions. Chapter 3 provides insight into a synergistic computational and experimental approach to improve the hydrogelation-ability of ionene polymer-based gelators. Despite the fact that gels provide numerous potential applications, still the mechanism of self-assembly and gel-formation is not fully understood and hence prediction of physical gel-properties remains challenging. Interestingly, we were able to demonstrate that gelation properties of polyelectrolyte hydrogels could be controlled by simple modification of the core-geometry of the polymers. Conclusions drawn from experimental observations were successfully confirmed by computational simulation techniques including DFT-calculations. Furthermore, gels based on the most efficient polymer exhibited a transparent appearance and the gel-network was able to disperse single-walled carbon nanotubes to produce organic-inorganic hybrid materials. The poor solubility accompanied by a high affinity towards aggregation is creating a problem for applications of nanotubes as molecular conductors, which could be solved by homogeneous dispersion in gel-materials. Chapter 4 focuses on the ultrasound enhanced gelation properties of a novel formamidine-based ambidextrous gelator. For a long time, ultrasonic treatment was thought to hinder self-assembling processes in solution. Hence it is very fascinating that treatment of isotropic solutions of the formamidine in various organic solvents resulted in much faster gelation kinetics in comparison to the classical heating-cooling protocol to induce gelation. Additionally, this phenomenon was accompanied by a severe reduction of the minimum gelation concentration and a significant enhancement of thermal and mechanical stabilities. The ambidextrous nature of the formamidine compound was revealed by applying a pH-gradient method to induce gelation in aqueous environments in a pH-range of 4.5-5.5, which could result in potential application in transdermal drug release. Furthermore, organogels revealed a smart colorimetric response towards several heavy metal-ions such as Cu(II), Fe(III) and Ce(IV), which could result in potential applications in sensing. Finally, chapter 5 deals with isosteric replacement of an amide-moiety inside a known gelator-structure by a triazole. The concept of bioisosteric replacement is well established in the field of biomedicine, but is has so far not been applied in material science. Heterocyclic compounds have been successfully introduced into parental drug systems as they exhibit enhanced stabilities against hydrolysis. Since the development of the copper and ruthenium catalyzed cycloaddition between azides and alkynes, triazoles represent the most common class of heterocycles in isosteric replacement applications. Additionally, triazoles share many common properties with amides such as a high dipole moment and the possibility to create hydrogen-bonds. In this context, gelation abilities of an amphiphilic amide-gelator and its triazole-analogue have been systematically studied. Interestingly, it was found that the amide-containing compound was a more effective gelator for apolar solvents whereas the triazole-compound exhibited superior properties in polar protic environments. Furthermore, hydrogels derived from the triazole were readily degraded in the presence of physiological buffers, which resulted in potential applications of controlled release of a model drug (i.e. vancomycin)