Advanced Synthetic Tools

Kinetics and Mechanism

Hybrid Material Design

Polymer Characterization

Advanced Synthetic Tools

Advanced Polymer Conjugation Protocols at Ambient Temperature

Advanced macromolecular design – ranging from block copolymer formation and end group transformations to surface modification – should be rapid, function under equimolar conditions and preferentially occur at ambient temperatures to allow for a maximum of simplicity as well as – importantly – bioorthogonality. One of our synthetic foci is thus the development of such rapid ambient temperature macromolecular transformation processes, which make use of, for example, Diels-Alder chemistry as well as efficient substitution reactions based on inorganic sandwich complexes. Typically, the carbon-sulfur double bond in activated thiocarbonyl thio compounds (which can also function as RAFT agents) acts as a dienophile in hetero Diels-Alder (HDA) reactions. So-called RAFT-HDA reaction sequences can be employed to rapidly construct complex architectures under very mild reaction conditions. In addition, HDA chemistry can be used to construct covalent dynamic systems, which we employ to construct self-healing materials and novel rapid processing composite materials. In addition, we develop highly efficient light triggered ligation chemistries – mostly based on pericyclic reactions – that fulfill the click criteria (refer to the separate explanation on this page). Typical examples include the formation of block copolymers within a few seconds at ambient temperature or the nickelocene based preparation of highly reactive cyclopentadienyl (Cp) capped macromolecules. In addition, such ambient temperature ligation protocols allow for the connection of biological molecules to synthetic polymer strands due to their bioorthogonal character.


Photo-Induced Orthogonal Modular Conjugation Chemistry

The introduction of the click chemistry concept has lead to the design of efficient synthetic pathways towards complex macromolecular structures and materials. For example, the modular conjugation concept allows the linkage of two endgroup functionalized polymers. To increase the diversity and orthogonality of modular ligation approaches, we investigate light triggered ligation reactions, for example Diels-Alder reactions, based on the in-situ formation of ortho-quinodimethanes that are suitable for complex polymer design. In combination with ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) the novel light-induced tools provides the opportunity for the rapid design of complex macromolecular architectures (such as combs and multi-block copolymers) under ambient reaction conditions. Other employed light triggered ligation protocols include the NITEC (nitrile imine tetrazole ene cycloaddition) approach, photo-triggered oxime ligations, several variants of phenacylsulfide chemistry or photochemical approaches based on phencyclones. Importantly, the developed tool box of light triggered reactions finds applications in our activities in the hybrid material design research program, most notably for spatially resolved (bio)surface design and in lithographic applications. Importantly, we develop light triggered chemistries that feature wavelength selectivity (such as the λ-orthogonal pericyclic photochemistry concept we introduced).


Macromolecular Sequence Control in Photonic Fields

Designing artificial macromolecules with absolute sequence order represents a considerable challenge. We employ advanced light-induced avenues to monodisperse sequence-defined functional linear macromolecules via unique photochemical approaches. The versatility of our synthetic strategies – combining sequential and modular concepts – enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass-spectrometry. Photochemical strategies are a viable and advanced concept for coding individual monomers units along macromolecular chains.


Supramolecular Precision Design

The combination of supramolecular binding principles (such as H-bonding and cyclodextrin host/guest interactions) with precision polymer design enables the generation of responsive polymer structures that we apply in the context of biomimetic reprogrammable materials and delivery system design. At the same time, the synthesis of such systems is one of our strength, specifically the synthesis of supramolecularly connected polymers by combining RDRP protocols (such as the RAFT process or ATRP) with cyclodextrin host/guest chemistry and (orthogonal) hydrogen bonding systems. A particular emphasis lies not only on the design of unipolar supramolecular polymer systems, yet also on the self-assembly processes induced by supramolecular amphiphilic block copolymers, including systems that can undergo transitions from amphiphilic to non-amphiphilic at a certain temperature. Critically, we exploit supramolecular associations in recodable surface design. The fundamental exploration of supramolecular binding principles inspires our reserach thrusts in rehapable materials design and gated single chain nanoparticle folding.


Facile Access to Complex Polymers via Reversible Deactivation Radical Polymerization (RDRP) Protocols

Free radical polymerization has been revolutionized by the advent of methodologies that can significantly extend the lifetimes of the propagating radicals and minimize termination products, thus providing access to well-defined polymer structures with pre-determined molecular weights and low polydispersities. Most importantly, these protocols can be employed to construct complex macromolecular architectures of variable shape and form ranging from linear block copolymers to star and palm-tree like structures. We enjoy generating interesting and complicated polymer structures via sophisticated chemistries, including the development of novel controlling concepts. However, it is also important to develop methods which can arrive at complex architectures in straight-forward fashions, using few reagents and those preferably in one pot reactions. Typical examples of chemistries that we have developed in this field include a one pot reversible addition fragmentation (RAFT)/ring opening polymerization (ROP) process or mechanistic switches between different controlling concepts (such as RAFT and ROP) that give facile access to comb, block or block copolymers featuring degradable and non-degradable polymer strands. Other approaches include the initiator free fabrication of polymerizable macromonomers and their subsequent usage as macromolecular scaffolds in conjugation reactions or even facile transitions of end groups generated by the RAFT process (so-called RAFT to OH terminal switch). Typically, the polymerization concepts are combined with a ligation process and contribute significantly to our research program into hybrid material design.


Development of Advanced Methodologies to Control Polymerizations

While we rely on existing control methodologies for polymerization processes, we constantly strive to expand the existing technologies (e.g. by the design of novel functional and (photo)reactive reagents for reversible addition fragmentation chain transfer (RAFT) chemistry) or develop entirely new approaches to effectively control the position and polydispersity of the molecular weight distribution of variable (functional) polymers. Typical examples include polymerization control via spin trapping reagents (e.g. thioketones or nitrones). In addition, we strive to develop photochemically driven methodologies for the synthesis of sequence defined macromolecules, exploiting the orthogonality of light and thermally driven click ligation protocols.

 

 

 

Ambient temperature macromolecular transformations  in collaboration with cell biology groups of the kit, we are developing protocols that allow for a targeted attachment of cells to polymeric scaffolds generated by direct laser writing (dlw). it is the a



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Hybrid Material Design

Surface Chemistry Design for Targeted Cell Attachment
In collaboration with cell biology groups of the KIT, we are developing synthetic protocols that allow for a targeted attachment of cells to polymeric scaffolds generated by direct laser writing (DLW). It is the aim of the research to enable the introduction of targeted bio-functionalization points into nano-meter scale polymeric scaffolds with an extremely high spatial resolution via two photon processes. The bio-functional nano-meter scaffolds are employed for the study of cell behavior and differentiation.

Design of Polymerization Systems for 3D Microstructure Fabrication via Direct Laser Writing Lithography
In a joint effort, the Macroarc group and the team around Prof. Martin Wegener (KIT) combine modern lithographic methods (e.g. direct laser writing (DLW)) with advanced polymerization and ligation techniques. DLW is an efficient technique for 3D microstructure fabrication where structures are generated via two-photon polymerization by focusing a femtosecond laser beam into a photo-resin typically placed onto a glass slide and by moving either the slide or the laser focus. While the overall DLW process has been an important research topic over the past decade, little emphasis has been placed on connecting modern polymerization and efficient ligation techniques to this research area. The majority of photo-resins employ either free radical polymerization or cationic polymerization for microstructure generation. By introducing a variety of polymerization / ligation protocols novel to DLW, understanding of the overall process can be improved and fine-tuning of a variety of structural parameters can be addressed in numerous ways. As an example, both radical thiol-ene and thiol-Michael addition reactions have recently been introduced into the fabrication and surface modification of complex 3D microstructures via DLW. While radical thiol-ene polymerization is employed for the fabrication of the insoluble polymer structures, remaining thiol moieties can readily be addressed in subsequent surface modification reactions with different functional maleimides. Typical characterization methods include IR spectroscopy, scanning electron microscopy, laser scanning microscopy and X-ray photoelectron spectroscopy.


Direct Laser Writing beyond the Diffraction Limit
Jointly with our close partner, the group of Prof. Martin Wegener at the KIT, we explore photochemical processes that allow to reduce the writing line width in 3D laser lithography. Specifically, we exploit stimulated emission depletion (STED) concepts pioneered by Nobel Laureate Stefan Hell and transfer these into the chemical realm of STED photoresist design. A first example based on our photochemistry tool box demonstrates that photocaged dienes (so-called photoenols) can be effectively used to reduce the line width to close to 50 nm when writing with 700 nm in a two photon process. Ultimately, we aim at line width of around 10 nm being written with visible light irradiation, which has the potential to affect entire fabrication sectors.

Surface Modification and Nanoengineering
While we have a keen interest in generating non-tethered macromolecular architectures, we are also actively engaged in applying living/controlled free radical polymerization protocols towards the functionalization of surfaces. Of particular interest are modifications of micro- and nanospheres which find use in biomedical applications such as bio assays and drug delivery vectors. For example, non-degradable microspheres are generated via precipitation polymerization of difunctional monomers – often in the presence of specific RAFT agents – and are subsequently surface modified via grafting from or grafting to approaches. Grafting to approaches makes use of a variety of conjugation protocols and the grafted moieties range from specific proteins to biodegradable polymer strands. Alternative scaffolds under investigation include carbon nanotubes and a wide range of planar arrays, including biomaterials such as cellulose and hyaluran. A particularly important aim is to protect surfaces (including cellulose) against biofouling and protein adsorption. Typical techniques to characterize the modified surfaces include XPS, ToF-SIMS, ATR, FT-IR microscopy, solid state NMR, SEM as well as fluorescence microscopy.

Biosurface Modifications

The modification of biosurfaces on the micrometer scale determines their macroscopic properties. Especially the most important skeleton builder in nature - cellulose - is a suitable platform for bio-polymer hybrid conjugation as well as for the immobilization of proteins. For these purposes highly effective reaction protocols such as RAFT- or ATRP polymerization in combination with click chemistry are applied to result in a broad variety of smart bioactive surfaces which are applicable in fields such as coatings, films, membranes, pharmaceuticals or nutrients. Additionally to the common surface characterization methods XPS, solid state nmr and fluorescence microscopy, we analyze these samples with state-of-the-art FT-IR microscopy. Our biosubstrate functionalization research program is pursued in close cooperation with the group of Prof. Hans Börner (Humboldt University in Berlin).


Biomimetic Materials


Mimicking natural materials via synthetic means is a key challenge in contemporary polymer science. Within one of our research strands we aim at the preparation of bioinspired surface coating technology combining our own surface modification technologies (such as highly efficient photo-triggered and thermal orthogonal ligation protocols) with those provided by nature. Further, we aim at advancing along the pathway of synthetically producing molecules that can - at one time in the future - mimic the behavior of natural biomolecules and nacre. For these purposes, we combine precision macromolecular design with supramolecular chemistry.


Covalent Surface-Functionalization of Carbon Nanotubes (CNTs) and Fullerenes

Inspired by the emerging applications of fullerenes and CNTs in nanotechnology, photo-electronics, optics and in the field of nanocomposites, we are interested in covalent surface-functionalization strategies of these materials. Fullerenes and carbon nanotubes act as dienophiles when mixed with an appropriate diene (cyclopentadienyl) end-capped polymer chain. In a one-pot reaction the chains are covalently grafted and thus impart physical and chemical properties of the attached polymer to the nanoobjects. Our strategy – based on a single Diels-Alder reaction – will provide opportunities to be applied for electronic devices and processing methods when modifying a polymer matrix with functional CNTs. Our CNT research program is carried out in cooperation with the Fraunhofer Institute of Technology (ICT) in Pfinztal as well as with groups at the KIT.


Precision Metallopolymer Design and Surface Encoding

Polymers containing metal centers within their backbone are fascinating materials, as they can be employed in a wide range of applications from opto-electronic devices to catalysis systems. In a close collaboration with the department of Inorganic Chemistry at the KIT (Prof. Roesky), well-defined metal containing macromolecules of variable architecture are generated. Metals of interest include mainly palladium and ruthenium, yet also iron, depending on the application. strategies to polymerize monomers containing such metal centers include step-growth polymerization as well as living/controlled radical processes in conjunction with efficient polymer backbone modifications. In addition to the precision metallopolymer synthesis, we are exploring avenues to encode variable metallopolymers in a spatially resolved fashion onto surfaces for applications in catalysis and electronics. The catalytic activity and the generation of suitable carrier materials is explored in collaborations with inorganic chemistry groups at the KIT and other partner universities.

 


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Kinetics and Mechanism

Modelling Complex Polymerization Mechanisms and Kinetics

To develop an effective synthetic approach to polymers with well-defined properties, an in-depth understanding of the underpinning reaction mechanism and kinetics is important. when the reaction mechanism of a polymerization (including the rate coefficients that govern the individual rate coefficients) is known, one can compute the entire polymerization process including the molecular weight and sequence distribution in advance without ever entering a laboratory. In our group, we use the powerful PREDICI software package to model polymerization processes and deduce kinetic rate coefficients of key reaction steps in a close interplay between experiment and simulation. Key objects of interests are the formation processes of complex architecture polymers (such as stars) and the understanding of acrylate reaction kinetics.


Fundamental Investigations into Polymerizations Mechanism and Kinetics
Related to the computer based modeling of polymerization processes, we have a keen interest in experimentally deducing the rate coefficients that govern the individual reaction steps in polymerization processes. These include the difficult to obtain termination rate coefficient, where we have developed a novel approach based on living radical polymerization to arrive in a relatively facile fashion at chain length dependent (CLD) termination rates (the so-called RAFT-CLD-T method). Similarly, we are deducing propagation rate coefficients for unusual monomer systems by employing a high frequency (500 Hz) pulsed laser system in conjunction with absolute molecular weight determination via triple detection size exclusion chromatography.

 


Molecular Approaches to Understanding Polymer Degradation
Understanding the degradation of polymeric systems is paramount for their use in a range of applications. Our group is currently active in employing SEC-ESI-MS technology to study the degradation of poly(methyl methacrylate) and poly(butyl acrylate) model compounds featuring variable end groups. ESI-MS is a powerful molecular mapping tool to study polymer degradation, which to the best of our knowledge has not yet been extensively applied to this problem set. We study degradation pathways of polymers (or their oligomeric model systems) with variable end groups, including those that feature end groups generated via living/controlled free radical polymerization protocols, with the ultimate aim of finding approaches to avoid degradation setting in or employing degradation as a targeted means to prepare nano-structured materials. In addition, we employ time resolved SEC, rheological tools (in collaboration with the group of Prof. Wilhelm) as well as extrusion experiments to specifically assess the stability of precision polymers prepared via living/controlled polymerization protocols as well as those prepared via modular ligation chemistries.

Photoinitiation Processes

A convenient route to generate free radicals – both industrially and academically – is via ultraviolet (UV) initiated processes. Typically, radical fragments are generated by either the direct formation of radicals from solvent and/or monomer units or by the decomposition of an added photoinitiator molecule. UV initiated polymerization – whilst having industrial applications in the curing of coatings – has especially been employed in conjunction with pulsed UV-laser initiation to obtain propagation and termination rate coefficients via the so-called pulsed laser polymerization – size exclusion chromatography (PLP-SEC) and single pulse – pulsed laser polymerization (SP-PLP) techniques. in the context of these techniques, initiation processes have been studied and the reactivity of the generated initiator radical fragments has been estimated. We employ soft ionization ms techniques to accurately map the groups generated under well-defined UV laser initiated polymerizations; the results support the idea that some initiators generate fragments of very variable reactivity, e.g. an initiator fragment that is mainly responsible for initiation processes and one which is almost exclusively undergoing termination. It is the aim of this research strand to employ SEC-ESI-MS to map UV initiated polymerizations with respect to the generated polymer end groups for a range of initiator systems as well as monomers in solvent and bulk systems. The overall aim is to arrive at a quantitative map of how photolytically generated radical fragments react with specific vinyl double bonds. Molecular weight control in UV-initiated systems (so that molecular weight of the polymers is suitably low for ESI-MS analysis) can be achieved via the RAFT processes (provided the RAFT agent is chosen judiciously to not decompose under UV radiation) as well as via the fast pulsing action of a UV laser. The results from the mass spectrometric investigations are combined with femto-second pump-probe experiments carried out in collaboration with the Physical Chemistry department at the KIT.


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Polymer Characterization

Imaging of Macromolecular Chain Structures via Electrospray Ionization Mass Spectrometry

We employ electrospray ionization (ESI) mass spectrometry (MS) techniques to generate accurate maps of the polymer chain distributions with respect to polymer end groups. Such soft ionization mass spectrometry techniques are powerful tools in providing detailed molecular information instead of giving bulk polymer information (as for example obtained from size exclusion chromatography measurements). Key areas of interest to us are the development of protocols that allow the efficient ionization of variable polymer structures ranging from the polar (such as polyacrylates) to the non-polar (such as polystyrenes), the determination of end group chemistries via ion trapping experiments as well as the increase of both sensitivity and resolution of synthetic polymer MS. We are also interested in the study of complex macromolecular designs (such as star polymers) via innovative ionization protocols. For these purposes, we employ linear, quadrupole ion trap instruments as well as orbitrap analysors.


Hyphenated LACCC-SEC Analysis

The analysis of complex macromolecular architectures is a key activity in synthetic polymer science. in our group, we thus apply and develop methodologies based on 2 dimensional chromatographic techniques for the analysis of advanced polymeric materials that we have synthesized. One of our favorite approaches is liquid adsorption chromatography under critical conditions (LACCC) coupled to size exclusion chromatography (SEC). Via LACCC-SEC, it is possible to image both the chemical and molecular weight heterogeneity of a polymer sample in a precise fashion. Knowledge about both parameters is especially important for the optimization of block copolymer synthesis via modular (ambient temperature) ligation chemistries, yet also in the mechanistic understanding of polymerization processes.


Quantitative Mass Spectrometry via Size Exclusion Chromatography – Electrospray Ionizations Coupling

Analysis of the full molecular weight distribution of polymers generated by kinetic experiments allows access to a number of important kinetic rate coefficients in free radical polymerization. Classical detectors used for the determination of molecular weight distributions by size exclusion chromatography (SEC) yield accurate information about the polymer concentration. The molecular weight axis though is uncertain in SEC and existing calibration procedures may introduce errors of up to 30% in the obtained molecular weights. chromatographic band broadening in SEC imposes further bias on the measured molecular weight distributions. Mass spectrometry has the potential to yield exact molecular weights of individual molecules. However, today highly accurate molecular weight distributions (MWD) with errors of less then 1% of synthetic polymers can only be obtained in very limited cases. This is because synthetic polymers do not exhibit one uniform chain length but rather a distribution of molecular weights. although in mass spectrometry the molecular weight axis is certain, due to instrumental bias and a potential dependence of ionization efficiency on molecular weight and charge-state, abundances of oligomeric ions are not an accurate description of oligomer concentration in the analyzed sample. This research theme aims at deriving accurate molecular weight information on polymers by coupling of size exclusion chromatography with ESI-MS and refractive index (RI) detection. Use is made of the high accuracy of individual molecular weights obtained by mass spectrometry and the possibility of using ESI-MS to depict the concentration profiles of oligomers eluting from the chromatographic column. absolute concentration information is gained solely from a concentration sensitive (RI) detector. A sophisticated deconvolution approach is applied for data processing. During the course of investigations, additionally to accurate molecular weight distributions, valuable information about the electrospray ionization process of polymers are be gained.
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