Authors: Tassilo Gleede
Source: Gutenberg Open Science (article, 2020-01-01)
Field: Chemistry — Organic Chemistry

Anionic polymerization of aziridines: Tuning block- and gradient-copolymer architectures and applications of linear polyaziridines 14 Years after anionic ring-opening polymerization was applied to activated aziridines for the first time, this rather novel monomer class became interesting for more and more research groups. The polymer class originated from activated aziridines offers several hidden potentials to be further explored e.g. their unique properties concerning the polymerization behavior and expanding the scope of new aziridine monomers to study functional polyamine derivatives. In contrast to cationic polymerization, anionic polymerization requires proton-free conditions, why the N-terminal hydrogen is substituted with a sulfonyl group which withdraws electrons from the aziridine ring and thereby allows nucleophilic attacks and consequently, living anionic polymerization. The polymers from activated aziridines represent functionalizable, linear polyamine derivatives or polysulfonamides. This PhD thesis focuses primarily on a deeper understanding of synthesizing gradient and block copolymers with aziridines as well as further explain the nature of aza-anionic polymerization to classify it next to other anionic polymerizations. In addition, this novel class of linear polyamine derivatives were investigated in fundamental studies on potential applications as cell transfection agents or as amphiphilic surfactants. The thesis itself is divided in six main chapters of published results, an outlook and appendix. The first Chapter is an introduction on polyamines synthesized from aziridines and azetidines. It provides an overview of different routes to access polyamines with various structures and refer to applications of those polyamine classes, introduces the different routes to synthesize the activated aziridines and summarizes the different polymerization techniques to access the polysulfonamides. The second chapter focus on the unique finding that anionic polymerization of aziridines appears to be tolerant and robust towards protic impurities. Further, this polymerization technique does not require inert atmosphere and stays living in the presence of large amounts of water or alcohols. Different activated aziridines were polymerized with up to 100-fold excess of an added protic impurity (like water or alcohols), proven to be active and fulfilling the requirements of a living polymerization. The electron withdrawing effect of the activating groups causes this unique tolerance towards protic additives. This effect decreases the basicity of the propagating species, while maintaining a strong nucleophilic character. Alcohol or water is only slightly involved in the polymerization, which further allows the direct preparation of polyols by anionic polymerization without protective groups. The third chapter demonstrates the first single step one pot copolymerization of activated aziridines with ethylene oxide (EO). Copolymerization of these two highly strained three-membered heterocycles results by a one-pot copolymerization to well-defined amphiphilic block copolymers with a single step. The polymerization was followed by real-time 1H NMR spectroscopy, finding the biggest reactivity difference of r1 = 265 and r2 = 0.004 for 2 methyl-N-tosylaziridine/EO and r1 = 151 and r2 = 0.013 for 2-methyl-N-mesylaziridine/EO ever reported for anionic copolymerizations. The obtained amphiphilic diblock copolymers were used to stabilize emulsions and to prepare polymeric nanoparticles by mini-emulsion polymerization. Synthesis strategies towards amphiphilic penta- and tetrablock copolymers in one or two steps are presented additionally in this section. These example of epoxide and aziridine copolymerizations represent a novel strategy to produce sophisticated macromolecular architectures. They are an ideal system to study stimuli-responsive and amphiphilic (block) polymers consisting of polyamines and water soluble polyglycols. The fourth chapter is dedicated to the individual copolymerizations of activated aziridines with two different activation groups. Due to the beneficial living nature of anionic polymerization, gradient copolymers can be obtained with low dispersities and adjustable molar mass. The great variety of the activation groups allows tuning the electron withdrawing behavior precisely and thereby the degree of the monomer activation. The combination of different activating groups allows further fine-tuning the gradient strength of copolymers. Sulfonyl activated aziridines are to date the only monomer class providing access to gradient copolymers with microstructures ranging from statistical to block-copolymers solely by adjusting the activation groups. This detailed study allowed correlations between the monomer activation given by Hammett parameters and the propagation parameters of the individual homo polymerizations. This is used to predict polymerization rates (kp) for aziridines, not synthesized so far. For the first time correlation of copolymerization ratios for ring-opening polymerization with the EWD nature of the monomers was possible. This knowledge allows accessing various tailored gradient copolymers with controlled monomer sequence in a single step and predicting copolymer structures of not synthesized monomers. The last two chapters (chapter 5 & 6) represent the synthesis of lately developed functional activated aziridines. In both chapters the obtained polysulfonamides were further used for post modification. As the anionic polymerization of sulfonamide-activated aziridines leads to polymers with a linear polyamine backbone, this pathway is after a successful desulfonylation an alternative to the 2-oxazoline route. Poly (2-oxazoline)s are usually used to access linear polyethyleneimine (L-PEI) after acidic hydrolysis from. The 1-(4-cyanobenzenesulfonyl) 2-methyl-aziridine, an aziridine containing a highly electron withdrawing activation group was found to polymerize as good as the other monomers of the aziridine family. Additionally, the 4-cyanobenzenesulfonyl allows mild reaction conditions to cleave the nitrogen – sulfur bond to convert the polysulfonamine into linear polypropyleneimine (L-PPI). The high control over molecular weight and weight dispersities achieved by living anionic polymerization are the key advantages of this strategy, especially if used for biomedical applications, as molecular weight correlates with toxicity. The synthesized polypropylene-imine showed further to be an adequate cell transfection agent. 4 Styrenesulfonyl‐(2‐methyl)aziridine (StMAz) is a monomer containing a functional activation group. This makes is the first orthogonal aziridine monomer, applicable for both anionic ring‐opening and radical polymerization. Both polymerization pathways are accessible without using protective groups. While azaanionic ring‐opening polymerization (AAROP) of StMAz and other methyl‐aziridine derivatives provides multifunctional polyaziridines, radical polymerization of the vinyl group gives access to polyalkylenes with aziridine side groups, which are known to be efficiently addressable via nucleophiles. Chapter 7 contains unpublished results on the synthesis and polymerization of enantiomerically pure aziridines. These and discussed applications correspond to an outlook on further research with activated aziridines. Copolymer ; Polymerization ; Polymer chemistry ; Block (permutation group theory) ; Materials science ; Polymer science ; Chemistry ; Polymer ; Mathematics ; Organic chemistry ; Combinatorics Synthetic Organic Chemistry Methods ; Carbon dioxide utilization in catalysis ; Synthesis and Catalytic Reactions