PhD Thesis
Click Chemistry as Efficient Ligation Strategy for Complex Macromolecular Architecture and Surface Engineering
Anja S. Goldmann (01/2006-02/2010)
Support: Axel H. E. Müller
Summary
Click chemistry was utilized as ligation strategy for the synthesis of cyclic polymers, surface modification of large microspheres and iron oxide particles. The broad spectra of this universal and powerful tool in complex macromolecular architecture and surface-functionalization is presented.
Cyclic polystyrene was synthesized by the combination of Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerization and the copper-catalyzed Huisgen [2+3] cycloaddition click reaction. Therefore, an azido dithiobenzoate click RAFT agent was employed as chain transfer agent in the RAFT polymerization of styrene resulting in low molecular weight azido-terminated polymers. The exchange of the dithio moiety of the polymeric chains was carried out by using an alkyne-modified initiator, leading to a heterotelechelic linear polymer precursor for the click cyclization. The properties of the macrocyclic polymer, as compared to the linear counterpart were investigated. The combination of several analytic methods proved the cyclic structure. From the viscosity measurements in the good solvent THF a contraction factor of g´ = [eta]cyc/[eta]lin =0.70-0.74 was calculated. This value is consistent with the theoretically calculated value g´=0.67 for theta-conditions.
Surface modification of large poly(divinylbenzene) microspheres (pDVB, 1.3 mikrom) was undertaken with two different strategies, on the one hand with Huisgen [2+3] cycloaddition reaction and on the other hand with thiol-ene click chemistry. The pDVB microspheres have a thin surface layer consisting of partially crosslinked and swellable poly(divinylbenzene) and contain vinyl groups on their surfaces which are accessible for modification, i.e. direct surface modification via grafting to techniques. The RAFT technique was used to synthesize SH-functionalized poly(N-isopropylacrylamide) (pNIPAAm-SH) polymers to generate surface-modified microspheres via thiol-ene reaction. Surface-sensitive characterization methods were used to identify the characteristic polymer shell on the outer layer. The visualization of the particles was carried out with Scanning Electron Microscopy (SEM). Suspension studies of the microspheres demonstrate an appealing gain of hydrophilicity when grafted with pNIPAAm45 and therefore could be suspended in water after surface modification. This observation was supported by a turbidimetric study. In an alternative approach, multifunctional azido-functionalized microspheres were prepared via the thiol-ene reaction of 1-azido-undecan-11-thiol with residual double bonds on the surface and subsequent 1,3 Huisgen dipolar cycloaddition reaction. These surface-modified particles are grafted with poly(hydroxyethyl methacrylic)acid (pHEMA). Grafting of hydrophilic polymers to hydrophobic particles can truly enhance the suspension properties of the particles in aqueous environment.
Finally, magnetite Fe3O4 nanoparticles were surface-modified by the Huisgen [2+3] cycloaddition reaction. A versatile biomimetic anchor, dopamine, was used to stabilize and concomitantly functionalize the particles. An alkyne-functionalized dopamine derivative was synthesized leading to multifunctionalized stable Fe3O4 nanoparticles. Surface modification was carried out with azide-endgroup modified polyethylene glycol (PEG). Furthermore, visualization of the surface-modified particles was accomplished by reaction with an azido-modified Rhodamine derivative and investigated with confocal fluorescence microscopy. With this approach, hydrophobic Fe3O4 nanoparticles can be converted into watersoluble particles. Furthermore the hydrophilic PEG-coating leads to a biocompatible shell.
In general, all these new applications show the versatility of click chemistry and broaden the scope of alternative and easy approaches for surface modification strategies and for the access towards complex macromolecular architecture.