Does it stick? Macromolecular building blocks for antifouling coatings

The undesired deposition of material onto a surface, also known as fouling, is a recurring challenge for many applications. The work described in this Thesis combines the fields of organic chemistry and surface chemistry for the development of antifouling coatings: from the synthesis of the macromolecular building blocks to their application on surfaces as coatings and testing of antifouling properties.

Chapter 1 of this thesis provides an introduction to the concepts of fouling and antifouling. The most applied antifouling coating are discussed alongside the most promising, state-of-the-art polymer materials that make up these coatings. Furthermore, macromolecules such as polymers and dendrimers that make for interesting candidates to serve as new building blocks for antifouling coatings are discussed. Especially dendrimers represent interesting candidates due to the high level of control over their architecture and the possibility for multivalent interactions. Zwitterionic dendrimers (ZID) are modified with an equal number of oppositely charged groups have found use in many biomedical applications. However, the design of and control over the synthesis of these dendrimers remains challenging, in particular with respect to achieving full charge-neutral modification of the dendrimer. In Chapter 2 the design, synthesis and characterization of fully zwitterionic, charge-neutral carboxybetaine and sulfobetaine zwitterionic dendrimers is described. Additionally, also the synthesis and characterization of ZIDs that contain a variable number of alkyne and azide groups are presented. Proof-of-principle coupling of an azide-biotin conjugate by click chemistry showed that these ZIDs indeed can be further modified. Especially the functionalized dendrimers are potential candidates for antifouling applications but also for biomedical applications such as drug delivery, since they allow straightforward anchoring or (bio)functionalization via click chemistry. 

To form an antifouling coating, the developed ZID needs to be coupled to a surface. Chapter 3 reports different strategies to enable covalent immobilization of ZIDs on a surface. The first explored method was amide bond-mediated binding of the ZID’s carboxylates to amine-terminated surfaces. Next to this, two types of click reactions, copper-catalyzed azide-alkyne cycloadditions (CuAAC) and thiol-yne chemistry, between pre-installed functional groups on the ZIDs and the surfaces were tested. These strategies all resulted in monolayers of ZID, although the two click chemistry-based routes yielded slightly higher levels of immobilized ZID, i.e., thicker and more hydrophilic layers. To further increase the immobilization load of the ZID, a grafting-through approach was tested that led to multilayers of ZID by reacting  methacrylate-functionalized ZIDs onto a pre-coated surface. The multilayers showed increasing thickness and hydrophilicity with each newly formed layer, and displayed antifouling properties that were slightly better than the oligoethylene oxide monolayers which were used as a reference.           
For these immobilization strategies, an undesirable surface pre-functionalization step was needed. To circumvent this, the macromolecules themself were designed to have an intrinsic affinity towards the surface. In the research described in Chapter 4, poly(l-lysine) (PLL) was used as a coupling agent. Two different routes were developed to synthesize polymer-dendrimer hybrids by the interconnection of PLL and ZID. The first route led to network-like structures in which PLL and ZIDs were crosslinked by multiple amide bonds. The second route led to a more defined, linear PLL-ZID macromolecule, which was formed via click coupling of multiple ZIDs to a single PLL backbone. These two different types of PLL-ZID systems were self-assembled onto silicon oxide surfaces from aqueous solutions to form thin, hydrophilic coatings. Especially the linear variant yielded good antifouling properties towards single-protein solutions and diluted human serum, as shown in detail by quartz crystal microbalance (QCM) measurements. The formed coatings could be further bio-functionalized using the remaining carboxylate moieties. An on-surface biofunctionalization step by biotin demonstrated the possibility to use the PLL-ZID hybrids coatings for selective detection of target analytes (streptavidin), while the underlying coating maintained its antifouling properties.

Chapter 5 presents possibilities to create poly(N-(2-hydroxypropyl)methacrylamide) (HPMA) polymer brush-based coatings without having to perform sensitive polymerization reactions on-surface. HPMA polymers were grafted form a PLL backbone to create a so-called “bottlebrush” polymer, which could self-assemble onto a surface in a similar fashion like the PLL-ZID copolymers reported in Chapter 4. Three routes towards such PLL-HPMA-coated surfaces were developed ranging from “classic” grafting-from to entirely grafting-to in order to compare differences in outcome and overall antifouling performance of the coatings. Additionally, a grafting-to bottlebrush was synthesized that contained 5% carboxybetaine in its side chains, which offered the possibility for further functionalization after an ester activation step. Eventually, all surface modification routes yielded coatings that showed single-protein antifouling properties.

Finally, in Chapter 6 the differently developed building blocks and coatings are discussed in terms of synthesis, antifouling properties and ease of application. The findings of this research are placed in a broader context and recommendations for further research are given.