RAFT polymerization from DNA for DNA-polymer conjugates and higher-ordered DNA-polymer architectures
FacultiesFakultät für Naturwissenschaften
InstitutionsKompetenzzentrum "Ulm Peptide Pharmaceuticals (U-PEP)"
Institut für Organische Chemie III (Makromolekulare Chemie und Organische Materialien)
External cooperationsMax-Planck-Institut für Polymerforschung
Cumulative dissertation containing articles
The attachment of synthetic polymers to biomolecules has resulted in a novel class of biomolecule-polymer hybrid materials, where the exceptional features of both molecules were combined in a synergistic fashion. Among these, DNA-polymer conjugates have emerged prominently due to the unprecedented degree of programmability and molecular recognition that DNA provides. Such DNA-polymer conjugates were in the past mainly accomplished by grafting-to strategies, where a synthetic polymer was bound to DNA through suitable coupling chemistries either in solution or on a solid support. However, the grafting-from approach, where a polymer is grown directly from the biomolecule, has recently accumulated attention, as it offers improved grafting-densities, simple chain length control, better yields and easier product purification. Recent progress in transferring polymerizations to ultralow volumes has allowed the first DNA polymerization in solution via atom transfer radical polymerization. While this approach is developing readily, reversible addition-fragmentation chain-transfer (RAFT) polymerization has not yet been introduced for DNA polymerization in solution. Crucially, RAFT polymerization bears the intrinsic advantage that it does not rely on metal catalysts and, moreover, has recently emerged as the method of choice for polymerization-induced self-assembly. These features rendered RAFT polymerization particularly attractive for achieving DNA polymerization, where it offered vast opportunities for the design of novel DNA-polymer conjugates. This thesis explored the first RAFT polymerizations from single-stranded DNA sequences in solution and the supramolecular assembly of DNA-polymer nanostructures synthesized by polymerization-induced self-assembly. The challenges involved in DNA polymerization regarding small volumes and low DNA concentrations were addressed by leveraging novel concepts of polymer chemistry such as enzyme degassing. Two major strategies (i.e., photoinduced and thermal RAFT polymerization) were individually developed and for the first time applied for RAFT polymerization from single-stranded DNA sequences in solution. Using these approaches, a variety of DNA-polymer conjugates and advanced DNA block copolymer architectures containing different functionalities were achieved from a range of monomers (i.e., acrylamides, (meth)acrylates). Notably, DNA RAFT polymerization was also established as a pathway towards stimuli-responsive and fluorescent DNA-polymer conjugates. Aqueous RAFT polymerization from DNA sequences was further expanded to polymerization-induced self-assembly, granting access towards sophisticated DNA-polymer architectures such as micelles and worms. These nanostructures could be further functionalized with complementary DNA sequences, thus introducing polymerization-induced self-assembly as a versatile platform technology towards functional DNA-polymer nanostructures. In addition to DNA polymerization, the dynamic covalent chemistry of boronic acids and catechols was herein established to mimic the behaviour of nucleobases in DNA. The system exhibited a dynamic behaviour of binding and displacement very similar to DNA and thus represented another key success in the design of synthetic codes that resemble the sequence programmability of DNA. In perspective, this thesis has contributed to the further development of interdisciplinary research at the interface between polymer science and DNA nanotechnology. DNA RAFT polymerization, in particular, has shown great potential for the synthesis of DNA-polymer conjugates and higher-ordered DNA-polymer nanostructures. Following this strategy and considering further progress in DNA nanotechnology and related fields, the herein developed techniques have provided the fundamental understanding for the design of novel polymer-based hybrid materials.
Subject HeadingsDNS [GND]
DNA nanotechnology [LCSH]