Maleimide-Functionalized Thiol Reactive Copolymer Brushes: Fabrication and Post-Polymerization Modification

Polymer brushes that present side chain functional reactive groups are attractive platforms for the development of functional surface coatings. From the wide spectrum of possible postpolymerization modification reactions, thiol-based conjugation chemistries are particularly appealing as they can be performed reagent-less under mild conditions and can allow the site-selective conjugation of biomolecules. This manuscript reports a direct approach for the preparation of maleimide-functionalized polymer brushes. These brushes were obtained by surface-initiated atom transfer radical copolymerization of poly(ethylene glycol) methacrylate and a furan-protected, maleimide containing monomer, followed by a thermally induced retro DielsAlder reaction to unmask the maleimide groups. The feasibility of these brushes to serve as a platform for postpolymerization functionalization was explored in a series of model experiments using a variety of low molecular weight thiols, including a fluorescent dye and a thiol-modified biotin-derivative. The biotinylated brushes were subsequently used for the immobilization of streptavidin-coated quantum-dots. The copolymer brushes presented in this manuscript are attractive since they combine the nonbiofouling properties of the poly(ethylene glycol) methacrylate monomer with the chemoselective reactivity of the maleimide containing monomer, which makes them an attractive platform, e.g., for the immobilization of biomolecules.

Mechanochemically Responsive Surfaces and Soft Tissue Adhesive Interfaces Generated via Controlled Radical Polymerization

Nariye Cavusoglu Ataman

Thin coatings applied to surfaces dramatically improve the properties of materials. Thus, they have found application in a broad variety of areas including biomedicine, nanotechnology, bioelectronics and optics, amongst others. Polymer brushes prepared via surface-initiated controlled radical polymerization (SI-CRP) techniques represent a versatile class of thin polymer coatings that provide manifold opportunities to engineer surface and interface properties. Densely grafted polymer brushes prepared via SI-CRP possess several attractive material properties such as low friction coefficients and the ability to prevent biofouling, which are related to the stretched conformation of the surface tethered polymer chains. Those distinctive characteristics of polymer brushes make them highly appealing to engineer the properties of functional interfaces. A first aim of this Thesis is to investigate the mechanochemistry of hydrophilic polymer brushes prepared via surface-initiated atom transfer radical polymerization (SI-ATRP) from silica substrates. The second aim of the Thesis is to explore poly(2-hydroxyethyl methacrylate) (PHEMA) based polymer brushes as soft-tissue adhesives in wet tissue environment. This Thesis is divided into four chapters, which are briefly summarized below. Chapter 1 provides a summary of recent literature that has reported detachment or degrafting of densely grafted hydrophilic polymer brushes from substrates upon exposure to aqueous media. The collective results from these reports suggest that swelling-induced stretching of hydrophilic polymer brushes lead to mechanochemical activation of the bonds near the brush-substrate interface and subsequently facilitates hydrolytic chain cleavage. Chapter 2 aims to shed light on the influence of two fundamental structural polymer brush parameters on the degrafting of surface-tethered, densely grafted polymer chains, viz. (i) the chemical composition of the ATRP initiator that is used to grow the polymer brushes and (ii) the effect of surface curvature. To this end, a series of poly(poly(ethylene glycol) methacrylate) (PPEGMA) and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA) brushes were grafted from both flat silica substrates as well as silica nanoparticles. Subsequently, the degrafting of the surface-tethered polymer chains was investigated in cell culture medium and phosphate buffered saline (PBS) using various techniques. The aim of the final two Chapters of this Thesis is less on exploring the chain conformation of polymer chains grafted by SI-CRP, but more to use the ability of SI-CRP to prepare thin polymer films that present a high surface concentration of functional groups to mediate soft tissue adhesion. Chapter 3 describes the preparation of photo-active poly(2-hydroxyethyl methacrylate) (PHEMA) brushes as soft tissue bioadhesives. Tissue adhesion in this Chapter is induced as UV-irradiation of PHEMA brushes converts the initially bio-inert side chain hydroxyl groups of these brushes into (putatively) aldehyde groups, which can react with amine groups present in the tissue. The prepared PHEMA brush coated substrates are biocompatible, which avoids fibrous capsule formation and presents functionalities that can be transformed, on-demand, from a non-reactive, non-adhesive state to a reactive, adhesive state in wet tissue environment. While the photoactivation of the PHEMA side chain functional groups is very efficient, it is not very well defined from a chemistry point of view. Chapter 4 therefore, explores an alternative photoactivation chemistry, which is based on the use of the diazirine motif. These diazirine motifs were incorporated in poly(2-hydroxyethyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (P(HEMA-co-PEGMEMA)) copolymer brushes via post-polymerization modification. These diazirine modified brushes are attractive as they may not only be activated by UV-light but also by electrochemical means.

EPFL2016

Succinimidyl Carbonate-Based Amine-Reactive Polymer Brushes: Facile Fabrication of Functional Interfaces

Harm-Anton Klok

Polymeric coatings that can undergo effective functionalization with ligands and (bio)molecules necessary for intended applications are widely employed to engineer functional interfaces. Herein, amine-reactive polymer brushes are fabricated using a succinimidyl group-activated carbonate monomer, and their facile post-polymerization functionalization is demonstrated through ligand-mediated protein immobilization and detection. Copolymer brushes containing varying amounts of the reactive monomer and an ethylene glycol-based methacrylate comonomer were obtained using surface-mediated reversible addition fragmentation chain transfer polymerization. Post-polymerization functionalization of the thus-obtained copolymer brushes with a fluorine-containing amine, namely, 4-(trifluoromethyl)benzylamine, demonstrated highly efficient functionalization at ambient temperature. To demonstrate possible applications, polymer brushes functionalized with a bioactive ligand, namely, biotin, were used to detect the target protein, streptavidin. The biotin-streptavidin interaction on brushes could also be employed to conjugate protein-coated quantum dots. Importantly, comparison of the attachment of 4-(trifluoromethyl)benzylamine on activated carbonate group-containing brushes with reaction of the same molecule on traditional active ester-based brushes demonstrated higher extent of conjugation to carbonate brushes. Finally, orthogonal functionalization of the copolymer brushes with an amino-functionalized molecule and a maleimide-containing fluorescent dye in spatial control using microcontact printing was demonstrated. One can envision that the facile fabrication and efficient functionalization of succinimidyl carbonate-based amine-reactive brushes afford an attractive platform for applications using functional interfaces for diagnostic purposes.

2021

Design of amphiphilic nanocapsules based on hyperbranched star-block copolymers for the encapsulation and the controlled release of olfactory compounds

Céline Ternat

Effective encapsulation of small, volatile, weakly water-soluble molecules such as flavors and fragrances is necessary to protect them from degradation, to increase their lifetime, and to improve their water dispersion and fixation depending on the substrate of interest. The aim of this project has been to improve encapsulation and release in order to optimize the performance of fragrance molecules in water-based household (detergents, softeners, etc.) and body care applications (shampoos, lotions, etc.), and fine perfumery applications. More specifically, the aim has been to investigate the effectiveness of "unimolecular micelles" based on amphiphilic multi-arm star-block copolymers with a hyperbranched core with more than 26 functional groups, a hydrophobic inner and a hydrophilic outer shell. These have been prepared from a commercial hyperbranched polyester macroinitiator (HBP) by ring-opening polymerization of ε-caprolactone, followed by the atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBuA). Hydrolysis of the tert-butyl groups has then been used to convert the poly(tBuA) blocks to poly(acrylic acid) (PAA), resulting in HBP-(PCL)p-(PAA)q pH-dependent amphiphilic star-block copolymers with good control of the molecular weight distribution. These were shown to form stable nanocapsules with a well defined core-shell architecture, as confirmed by thermal and microstructural characterization. The necessity of the core-shell architecture for the effective encapsulation of fragrance molecules in aqueous dispersion has been demonstrated by NMR (nuclear magnetic resonance). The extent of encapsulation reflects the dynamic equilibrium between the free molecules and the fragrance/polymer complex and is dependent on the octanol/water partition coefficient (logP) of the fragrance compounds, as demonstrated with a similar non ionic core-shell architecture HBP-(PBMA)37-(PPEGMA)39 composed of a hydrophobic poly(butyl methacrylate) (PBMA) core and a hydrophilic poly(polyethylene glycol) methyl ether methacrylate (PPEGMA) shell (provided by the Polymer Laboratory of the EPFL). The fragrance loadings in the polymer (HBP-(PCL)p-(PAA)q and HBP-(PBMA)37-(PPEGMA)39), which reached up to 30 wt% depending on the type of the fragrance molecule, were argued to be linked to their solubility in the hydrophobic core of the star-block copolymer. Moreover, under conditions representative of real applications (fine perfumery and softener applications) the star-block copolymers significantly extended the time over which the concentration of certain volatiles remained above the human olfactory threshold. Effective encapsulation and delayed release of small hydrophobic molecules was hence demonstrated to be possible with the present systems. The straightforward synthesis, tailorable chemistry and globular architecture of the star-block copolymers investigated here therefore offer promise for the development of relatively cheap encapsulants with affinities for specific components in fragrance packages, and release triggered by selected substrates according to their surface chemistry.