Synthesis, structural characterization and applications of hyperbranched polymers based on L-lysine

L-lysine is an essential a-amino acid and a necessary building block for all proteins in the body. As an essential amino acid, L-lysine is not synthesized by humans or animals. Industrially produced L-lysine has therefore a big market as food additive, e.g. in pig food. In the body, L-lysine plays a major role in calcium absorption, building muscle proteins, recovering from surgery or sports injuries, and the body's production of hormones, enzymes, and antibodies.1 From a chemical point of view, L-lysine is an AB2 building block that contains two amino groups and one carboxylic acid group, which makes it an interesting monomer for the synthesis of dendrimers and hyperbranched polymers. L-lysine indeed has been extensively used to synthesize dendrimers2-4 or conjugates of dendrimers and linear polymers.5,6 These dendrimers and linear-dendritic hybrid architectures have attracted interest for various medical applications, including gene delivery,3,6-8 as drug carriers,9 for the development of multiple antigen peptide systems,10,11 and as magnetic resonance imaging agents.12 The drawback of these dendrimers and linear-dendritic hybrid architectures is their time consuming synthesis and their expensive large scale production. This thesis evaluates the feasibility of L-lysine as a monomer to synthesize hyperbranched polymers and investigates the potential of these materials as encapsulation agents and for various biomedical applications. As the hyperbranched polylysines are prepared in a single step and can be produced conveniently at a large scale, they may offer an interesting alternative to their widely used dendritic analogues. Including this introduction, this thesis consists of 8 chapters, which are briefly described below. Chapter 2 gives a general overview of dendritic and hyperbranched polymers build up of amide bonds. Their synthesis and applications in medicine and catalysis as well as their self-assembling and encapsulation properties will be discussed. Chapter 3 reports on the synthesis of hyperbranched polylysines via the thermal polymerization of L-lysine hydrochloride.13 Different catalysts were investigated to improve the reaction kinetics. The structure of the polymers was determined by 1H-NMR spectroscopy, and the degree of branching and the average number of branches were calculated. Chapter 4 will discuss the feasibility of different approaches to control polymer architecture during the thermal hyperbranched polymerization of L-lysine hydrochloride.14 The reactivity of the more reactive ε-NH2 group was modulated by introducing temporary protective groups. The distribution of structural units was analyzed by 1H-NMR spectroscopy and the degree of branching and the average number of branches were calculated. Chapter 5 will describe the dilute solution and solid state structure of hyperbranched polylysines and polyelectrolyte complexes generated from hyperbranched polylysine and various anionic, sodium alkyl sulfate surfactants.15 Str