The advance of click chemistry has facilitated polymer synthesis and modification. This highly efficient and selective reaction toolbox is also very useful for functionalization of polymer assemblies, such as polymer vesicles or polymersomes. In our group we have applied both Cu-assisted (CuAAC) and strain-promoted (SPAAC) azide-alkyne coupling strategies to add novel properties to polymersomes. Functionality can be added both on the polymersome surface or in the bilayer. After showing in the past that CuAAC works well for the peripheral attachment of both small fluorescent probes and large biomolecules such as enzymes, we have recently conducted a comparative study with regard to different types of SPAAC reactions. It was shown that the intrinsically most reactive groups (dibenzocyclooctynes) only show their activity in coupling to azides when they are introduced after polymersome formation had taken place. When these click probes are present in the block copolymer upon formation of the polymersomes, the more hydrophobic nature of these groups results in a shielding in the hydrophobic polymersome bilayer, and therefore diminished accessibility compared to other, more hydrophilic, click probes.
Block copolymers with click moieties in the side chain of the hydrophobic block lead to the formation of polymersomes which can subsequently be stabilized by a click crosslinking reaction. We have taken advantage of this feature by constructing polymersomes which are used for the preparation of Pickering emulsions. As these assemblies are positioned at the interface of water and toluene, crosslinking was necessary to prevent dissolution and destabilization. By loading enzymes either in the water phase or in the aqueous lumen of the polymersome, a highly efficient biocatalytic transformation could be performed, due to the increase in contact area between enzyme and organic substrate. This crosslinking approach could also be used to directly introduce catalysts in the hydrophobic bilayer of the polymersomes, which showed similar performance as if they were not in water but in an organic solution.

Stimuli-sensitive nanoparticles can substantially improve the therapeutic landscape of a drug by enhancing its target-specific accumulation and reducing off-target toxicity. We designed pH responsive nanoparticles based on PEG-poly(propargyl L-glutamate) (PPLG) block copolymers with clicked amino side groups that yield a pH sensitive solubility shift; this shift allows the endosomal/lysosomal pH change to regulate intracellular delivery and reduce extracellular toxicity of the active drug. The base block copolymer, PEG-poly(propargyl L-glutamate) (PEG-PPLG) was prepared by the N-carboxyanhydride (NCA) mediated polymerization of propargyl-L-glutamate, initiated by amine terminated PEG of different molecular weights (5kDa and 10kDa).The pendant alkyne groups of PEG-PPLG copolymer were coupled to a library of azido modified dialkylamines through Cu-mediated 'click' chemistry. The molecular weights of these copolymers were found to be 15 kDa to 20 kDa with maximum polydispersity index (PDI) of ~1.1. The copolymers self-assembled into nanoparticles in pH 8.0 and the size of the nanoparticles was governed by the PEG molecular weight, degree of polymerization, and the structure of amine side chains. Static light scattering and transmission electron microscopy (TEM) suggested that the nanoparticle assemblies were vesicular in nature. The vesicles were found to withstand physiological salt and serum conditions and exhibited substantial buffering capacity from pH 6.0 to 7.2. Fluorescence spectroscopy experiments showed a sharp reduction in the emission intensity of a FRET acceptor located within the nanoparticle interior as the pH was progressively lowered indicating pH-responsiveness of the self-assembly. It was found that the vesicles prepared from PEG5K-PPLG with diisopropyl side chains were able to encapsulate 33% of the added amount of doxorubicin. These nanoparticles were able to release the encapsulated doxorubicin in a pH dependent manner. The copolymers did not show any level of cytotoxicity while doxorubicin loaded copolymer nanoparticles demonstrated an IC50 values higher than that of free doxorubicin. Furthermore, confocal microscopic experiments showed perinuclear accumulation of doxorubicin as punctate structures in chloroquine treated [pH-clamped to 7.4] MDA-MB-468 cells likely due to the presence of intact nanoparticles at this pH. The release of doxorubicin and its trafficking to the nucleus was observed for untreated cells, indicating the dissociation of nanoparticles due to the endosomal acidification. Fluorescence imaging on the basis of FRET revealed that most of the administered nanoparticles were cleared from the animal after 24h. Subsequent use as therapeutic delivery systems was investigated against MDA-MB-468 xenografts in NCR nude mice, whereby repeated administration of doxorubicin-loaded nanoparticles intravenously were found to suppress tumor growth for up to 20 days compared to the rapidly growing untreated control.

Biologically derived materials offer a high degree of complexity that synthetically assembled materials, thus far, have only attempted to mimic. A prime example representing the intricacy presented by biologically derived materials are proteins and their truncated equivalents, peptides. Proteins and peptides have a layered sophistication consisting of their primary structure or amino acid sequence, a secondary structure describing the molecular conformation, the tertiary structure detailing interaction between residues comprising the peptide and a quaternary structure resulting from the ability of multiple molecules to associate with one another. Taking advantage of new theory and mathematical modeling to predict peptide sequences that form desired intra- and intermolecular material structure, coiled-coil bundles have been constructed. Furthermore, through predictive modeling, the influence of the inclusion of non-natural amino acids in the peptide sequence on the stability of the coiled-coils has also been predicted.
Using this de novo approach, reactive functionalities conducive with click chemistry, including thiol and alkynes, were incorporated in peptide sequences. Once synthesized, the peptides decorated with these clickable motifs were placed in the proper solution environments and allowed to self-assemble into coiled-coil constructs. Confirmation of the formation of the assembly of the coiled-coils was attained through CD spectroscopy and dynamic light scattering experiments. After verification of the presence of coiled-coils, click chemistry was employed to link the coiled-coil assemblies together and form a network with predictable, desired dimensionality (i.e. 2-d vs. 3-d) and pore size between coiled-coil bundles. To incite network formation, photo initiated thiol-ene and azide/alkyne Huisgen click reactions between side chains residues on the coiled-coil and suitably functionalized crosslinkers were implemented. The linking of coiled-coils and subsequent material formation was assessed and monitored using dynamic light scattering and cryo-TEM. Reversibility of the material nanostructure with temperature by melting of the coiled-coils will also be discussed.

A new paradigm encompassing several distinct chemical reactions and, more importantly, a generalized approach to molecular design and synthesis has been rapidly adopted in the fields of chemical synthesis, biotechnology, materials science, drug discovery, surface science, and polymer synthesis and modification. The Click Chemistry paradigm focuses on implementation of highly efficient reactions that achieve quantitative conversion under mild conditions. As such, these reactions represent ideal candidates for further development, understanding and implementation. In particular, the synergistic combination of these click chemistries with photochemical initiation and polymer formation has been used to afford 4D control of polymer formation, structure and patterned assembly. Here, we will focus on two vignettes related to our implementation of photoclickable polymer systems. The first of these focuses on the development of covalent adaptable networks (CANs) where the ability to controllably alter the network structure is used to alter topography and other material properties by forming materials which can be switched revesibly from elastic to plastic simply by exposure to light. Secondly, we will focus on the development of approaches to photoinitiate the Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Here, implementation of this reaction in surface modification, hydrogel formation, and lithography as well as in the development of a new class of photopolymerized polymer networks will be presented.

Controlled radical polymerization processes have emerged as one of the most powerful synthetic strategies for the preparation of functional materials. The ability to regulate these processes with an external stimulus would dramatically increase their utility and facilitate an even greater range of applications. This presentation will detail the development and applications of a practical radical polymerization process that affords both spatial and temporal control over the chain growth process through mediation by light. Insight into catalyst structure activity relationships for this reaction, as well as applications that take advantage of the spatial and temporal control allowed by this system will be detailed.

Due to the presence of the thiocarbonylthio end-group, polymers synthesized via RAFT polymerization lend themselves particularly well towards post-polymerization modification through thiol-based “click” chemistries, such as the thiol-Michael reaction.[1] In this context the RAFT end group acts as a masked thiol which can be liberated by treatment with a nucleophile, most commonly an amine.[2]
Recently we have reported new acid/base “switchable” dithiocarbamates that offer a high level of control over polymerization of both “more-activated monomers” (MAMs, i.e. (meth)acrylates, (meth)acrylamides, styrenics) and “less-activated monomers” (LAMs, i.e. vinyl esters, vinyl amides).[3-5] This is accomplished by using the "switchable" RAFT agent in either its protonated (activated to control MAM polymerization) or neutral (deactivated to control LAM polymerization) form. This new class of RAFT agent allows access to polyMAM-block-polyLAM copolymers, with narrow molecular weight distributions, which are unobtainable using standard RAFT techniques.
To date, however, no post-polymerization modifications of the switchable dithiocarbamate group have been reported. In comparison to the facile transformation of dithioester and trithiocarbonate derived polymers to thiols, the reduced reactivity of dithiocarbamates[6] (e.g. towards nucleophiles) has the potential to limit the efficiency of post-polymerization functionalization through the thiol-Michael reaction and related routes. In this presentation the applicability of thiol-based conjugation chemistries on polymers that possess a switchable dithiocarbamate end-group will be discussed.
1. M. A. Harvison and A. B. Lowe, Macromol. Rapid Commun., 2011, 32, 779-800.
2. G. Moad, E. Rizzardo and S. H. Thang, Polym. Int., 2011, 60, 9-25.
3. M. Benaglia, J. Chiefari, Y. K. Chong, G. Moad, E. Rizzardo and S. H. Thang, J. Am. Chem. Soc., 2009, 131, 6914-6915.
4. D. J. Keddie, C. Guerrero-Sanchez, G. Moad, E. Rizzardo and S. H. Thang, Macromolecules, 2011, 44, 6738-6745.
5. D. J. Keddie, C. Guerrero-Sanchez, G. Moad, R. J. Mulder, E. Rizzardo and S. H. Thang, Macromolecules, 2012, 45, 4205-4215.
6. D. J. Keddie, G. Moad, E. Rizzardo and S. H. Thang, Macromolecules, 2012, 45, 5321-5342.

The lecture will present our most recent advances in the development and application of light induced catalyst-free, ambient temperature ligation chemistries for the spatio-temporal controlled encoding of 2- and 3-dimensional scaffolds, including those generated via direct laser writing and click chemistry based variants thereof. The underpinning chemistries include the light triggered formation of precursors for Diels-Alder conjugations, photo-insertions, tetrazole, phencyclone and phenacyl light activated systems as well as photo-triggered oxime ligations. Applications of the photo-patterned surfaces (with synthetic polymer strands and biomarkers) for targeted cell attachment as well as solution based photo-chemically driven polymer designs will be addressed. In addition, the lecture will cover the generation of photo-click-patterned biomimetic and cell directing materials. The structure of the generated surfaces is characterized in detail via photo electron X-ray spectroscopy (XPS) as well as time of flight secondary ion mass spectrometry (ToF-SIMS), while the solution based materials are characterized via hyphenated chromatographic techniques (SEC-ESI-MS, LACCC-SEC).

“Click” and highly efficient reactions have proven useful in almost every step of synthetic polymer chemistry comprising monomer synthesis, functionalization of polymeric building blocks with varying moieties (polymer-analogous reactions), formation of blockcoplymers or surface functionalization using end-functionalzed polymers.
This is extremely important for polymer-analogous reactions because unreacted functionalities will remain “part of the system”. In particular, the copolymerization of double-bond containing monomers can be used to build various kinds of polymers (poly(2-oxazoline)s, poly(ethylene glycol), poly(N-iso-propylacrylamide)) with pendant double bonds that represent suitable building blocks for thiol-ene (TE) reactions with different thiosugars. As an alternative approach, poly(pentafluoro styrene) is prone to undergo nucleophilic substitution in para-position of the aromatic rings when reacted with thiols (sugars and / or suitable terpyridine ligands). Based on the choice of the initial polymer, the resulting glycopolymers exhibit thermo-responsive properties, are bio-compatible or form micelles in aqueous solution while the nature of the chosen carbohydrate triggers the cellular uptake of the entire polymer.
Polymers that contain both reactants for the “click” reaction (furan and maleimide) can be obtained by copolymerization of suitable methacrylate monomers. In this case, a Diels-Alder reaction (DAR) results in crosslinking, whereas a consecutive Retro-Diels-Alder reaction at elevated temperature will open the network. Thus, self-healing materials are obtained. As an alternative, one reactant of the DAR (furane) can be incorporated to a poly(ethylene)oxide-based block copolymer, and the reversible crosslinking is achieved by addition of a bis-maleimide.
In addition, the 1,3-dipolar cycloaddition (CA) “click” chemistry of end-functional polymers has proven useful for the interconnection of different kinds of polymers. As an example, the functionalization of star-shaped poly(capolactone) with water soluble polymers in the shell results in promising materials for drug delivery purposes due to the resulting amphiphilic core / shell structure. Full exploitation of the living cationic ring-opening polymerization of 2-oxazolines even allows the preparation of a universal scaffold that can be functionalized in one pot by three orthogonal “click” reactions (CA, TE, DAR).
Conversely, “click” chemistry is useful already for the easy and straightforward preparation of functional monomers, such as methacrylate-functional metal complexes [10], or glyco-monomers. This represents the route of choice whenever one specific functionality providing the desired properties (such as light emission or cell targeting) has to be incorporated to a range of different polymers.

Microstereolithography (µSL), the fabrication of 3D microstructures through photopolymerization, is an impressive and potent tool used in many emerging technologies, such as photonic crystals, micromachines, and cell scaffolds for tissue engineering. One of the challenges faced by µSL is accurate fabrication of overhanging, high aspect ratio, or freely-moving parts. Feature collapse or sedimentation can occur without the use of temporary support materials, which can be costly or difficult to remove for certain geometries. Here, we demonstrate a dual-cure photoresist for layer-by-layer fabrication of 2D and 3D microstructures, which provides inherent support for all structures being formed, while simultaneously allowing a route for simple removal of unexposed material. The thermoreversible Diels-Alder “click” reaction was used to form polymer networks encapsulating acrylate monomers and photoinitiator. When polymer films were selectively photopatterned, both acrylate and unreacted maleimide polymerized, rendering a permanent network structure. Removal of unexposed material during the development step was achieved at 120°C, where the Diels-Alder equilibrium shifts towards the reactants and the network depolymerizes. Free acrylate and maleimide groups were shown to tolerate these development temperatures, with no evidence of side reactions in unexposed regions. A reliable process was developed for the fabrication of 3D microstructures using a mask alignment system. Finally, in perhaps the clearest sign of the system&’s versatility, mechanical properties were easily tailored by adjusting the choice of monomers and weight percentage of added acrylates.

In the past 20 years, copper, especially Cu(I) species, has been heavily involved in lots of important discoveries, notably copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions and atom transfer radical polymerization (ATRP) reactions. While those two novel approaches provide numerous advantages in polymer and material research areas, however, most of related researches and techniques developed in such area lack 4D spatiotemporal control, which can be readily improved by incorporating photochemistry. Recently, a novel copper containing photoinitiator, copper (II) acylphosphinate, has been proposed and subsequently synthesized in order to solve such problem. Such copper complex not only combine copper, ligands and photoinitiator in a single molecule, which would dramatically simplify the formulation process, but also exhibits great solubility in both aqueous and organic media which most commercially copper complexes lack. Upon light exposure, the anion, which is considered a type of traditional phosphine oxide photoinitiators, can be readily cleaved to generate radicals, which in turn reduce the Cu(II) species to the corresponding Cu(I) species in situ, to kick off either CuAAC or ATRP reactions with great control. Such properties along with the great solubility it exhibits make it a promising reagent in forming hydrogels, functionalizing polymer surface, fabricating particles or other related areas using either CuAAC or ATRP technologies. In addition, it provides a simple route to simultaneously performing CuAAC and ATRP reactions to produce polymers in bulk with interesting mechanical properties.

Global energy and environmental concerns create an urgent need for new functional materials to be used in areas such as energy conversion and generation, carbon capture and storage, catalysis and gas separation. To mitigate energy generation-related CO2 emission, much effort has been devoted to explore suitable materials for selectively capture CO2 in an energy-efficient, environmental-friendly and cost-effective processes. Porous materials relying on physical adsorption of CO2 are potential candidates to accomplish this goal because of their low regeneration energy consumption and high gas sorption capacity. Currently, design and fabrication of porous material with exceptionally high capacity and selectivity toward CO2 adsorption at atmospheric pressure is a great challenge. Microporous polymers are being intensively investigated to address this challenge owing to their intrinsic properties of large specific surface area, narrow pore size distribution, high chemical stability, low skeleton density, and the ability to be fine-tuned in their properties at the molecular level, allowing facile construction of porous materials with desired functionalities by appropriate choice of building block. Such organic porous structure has flexibility of varying in designing organic functional monomers and pendant functional moieties, and can be effectively combine the organic synthetic methodologies with processability of polymer, thus providing a unique opportunity for rational design and development of versatile microporous polymers for targeted applications.
In this study, we report the synthesis of triptycene-based microporous polymer with pending tetrazole moieties for high and selective CO2-capture application. Our design employs triptycene as the building block. This building block is rigid, which enables the preparation of permanently porous material. Furthermore, this building block is rich in aromatic rings and has many potential reaction sites for constructing diversify materials by post-modification. The key to our approach for improving selective CO2-capture is to combine CO2-philic tetrazole moieties into triptycene-based micorporous polymer via ZnCl2-catalyzed post-polymerization modification using the click reaction. Recent research has proven that the incorporation of N-containing organic heterocyclic groups (e.g. pyridine, imidazole and tetrazole) exhibits favorable polymer-CO2 interactions, resulting in polymer with high CO2 adsorption energies. But the post-modification of the microporous polymers is difficult. Our experiments indicate that the triptycene-based micorporous polymer with pending tetrazole moieties possesses high CO2 uptake capacity, reaching 134 cm3 g-1 (26.5 wt%) at 1.0 bar and 273 K, along with high selectivity towards CO2 over N2 and CH4. The micorporous polymer presents a promising potential as efficient adsorbents in clean energy applications.

Intramolecular activation by an internal nucleophile, as observed in anchimeric assistance, has long been employed as a means of increasing the efficiency of nucleophilic substitution reactions. We have prepared a new class of polymeric materials by living radical polymerization techniques that undergo facile nucleophilic substitution as a result of anchimeric assistance using a post-polymerization functionalization strategy. The modularity of this substitution has enabled the preparation of a range of derivatives with properties that vary with the identity of the nucleophile. The presence of an internal nucleophile opens up the possibility for reversible substitution reactions. We are currently exploring this behavior to prepare dynamically substituted and cross-linked polymers. The ability to incorporate this substitution function into random and block co-polymers enables further tuning of bulk properties through careful selection of co-monomers. In this presentation, we will disclose the preparation and properties of these versatile substitutable materials. We acknowledge the NSF and NSF GRFP for support of this work.

This presentation demonstrates that covalently functionalized multiwalled carbon nanotubes (MWCNT) with a silicone copolymer via nitrene chemistry (similar to click chemistry) can be used as efficient conductive fillers for the silicone dielectric elastomer actuators. The MWCNTs were covalently functionalized with poly(azidopropylmethyl)-co-(dimethylsiloxane) (silicone-N3) bearing an azide group through a nitrene addition reaction. The incorporation of a small amount of the uniformly silicone grafted MWCNTs (silicone-g-MWCNTs) in silicone dielectric elastomer strongly enhanced the mechanical, dielectric, and electromechanical properties of the resulting nanocomposites. This reinforcing effect is attributed to the homogeneous dispersion of silicone-g-MWCNTs in the silicone elastomer matrix due to the large degree of compatibility between the matrix and the passivation layers of the functionalized MWCNT.

A series of thiol monomers were shown to copolymerize with two rigid rod vinyl monomers. These thiol-ene polymerizations were performed under 254 nm ultraviolet light, with or without the use of photoinitiators. It was observed that the polymerization proceeds more steadily when the suitable photoinitiators and solvents were chosen. The pre-stressed and as-cast polymeric films were characterized using Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), Polarized Light Scattering (PLS), X-ray Diffraction (XRD) and stress/strain experiments. It is found that, the non-crosslinked polymer samples showed typical thermal characteristics of the main-chain liquid crystalline structure, while the crosslinked samples possessed that of liquid crystalline networks (LCNs). After loading with large stress on the LCN, a phase transition from a polydomain structure to a monodomain structure was observed. The monodomain LCNs show the characteristic anelastic property. Upon heating the largely pre-stressed LCNs from room temperature (which were in monodomain state) recovered to the original film dimensions. The shape recovery is attributed to the structural change from the monodomain to the polydomain state.

Polymerized ionic liquids (PILs) are unique polyelectrolytes with cationic and anionic groups included in the repeating unit. They are extremely attractive in the field of materials science as they combine the properties of ionic liquids (high ionic conductivity, thermal and chemical stabilities) with those of polymers (mechanical stability, processing and tunable macromolecular design). PIL elastomers, networks and gels are particularly used as solid or quasi-solid polyelectrolytes in applications such as dye sensitized solar cells, batteries or membranes for carbon dioxide recovery. In all these applications, imidazolium-based PILs are by far the most widespread and investigated materials. Since the striking development of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) modular ligation, a large variety of materials containing 1,2,3-triazole groups have been reported. We have recently pioneered the synthesis of 1,2,3-triazolium-based PILs, and their synthesis through CuAAC offers unprecedented structural design opportunities. PIL elastomers or networks are generally obtained by curing of charged linear polymers or by simultaneous polymerization and crosslinking reactions. This work describes a novel monotopic approach for the elaboration of PIL elastomers which is solvent- and catalyst-free, easy to process and applicable to a broad range of processing methods and applications.

A thiolactone-based approach for the solid-supported preparation of multi-functionalized, sequence-defined oligomers was successfully developed. The proposed two-step iterative protocol, consisting of an on-resin aminolysis and subsequent chain extension via Michael addition, is protecting group-free, relies on the use of a single, readily available thiolactone-acrylamide building block and several functionalized oligomeric sequences were obtained by consecutive use of a variety of commercially available amines. The obtained short sequence-defined motifs featuring a unique backbone and a pre-programmed organization of functional side chains, could potentially exhibit particular folding and self-association properties, predominantly determined by the nature of the functional amines. In this regard, high-througput automation and control over the stereochemistry, induced by the use of enantiomerically pure building blocks, will be further explored. Moreover, these heterotelechelic oligomeric species could, upon the installation of the appropriate functional end-group, be susceptible to periodic polymerization, affording sequence-controlled polymers. This promising reconstitution approach relies on the efficient application of thiolactones as latent thiol func-tionalities and will be the focus of our future research efforts.

A quantitative, additive free and one-pot reaction cascade involving the ring-opening of a thiolactone by primary amine treatment and subsequent conversion of the released thiol groups via Michael addition to an acrylate has been utilized for the double modifica-tion/functionalization of poly(N-isopropyl acrylamide) yielding tailor-made thermoresponsive polymers. After proving a quantitative double functionalization, different amine/acrylate combinations were employed in order to demonstrate the general applicability of the concept. Cloud points can be tuned by adjusting the amount of ring-opening amine in the reaction mixture, which enables to control the degree of modification. (1)
(1) Reinicke, S.; Espeel, P.; Stamenovicacute;, M.M.; Du Prez, F.E. ACS Macro Letters 2013, 2, 539-543.

The substitution chemistry of 2,6-disubstituted 9-aza- and 9-thiabicyclo[3.3.1]nonanes constitutes a connection reaction of sufficient reliability to be placed in the “click chemistry” class. An unusual feature of these linkages is their reversibility when the entering nucleophile is also a good leaving group. The synthesis, reactivity, and incorporation of these groups as main-chain, side-chain, and surface-displayed connectors will be discussed. In an aside for those who use the copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a brief summary of the mechanistic features of the process and the use of its best catalysts will also be provided.

Tissue engineering represents a promising approach for the treatment of large bone defects, in which biomaterials are seeded with cells that are expected to promote bone reconstruction. Bone cell colonization of the synthetic implant, especially in the inner area, remains a major challenge in bone tissue engineering due to the lack of nutrients and oxygen in the inner area and the accumulation of metabolic wastes, which can induce cell migration to the surface.
After having developed a biocompatible protocol for bone cell surface functionalization by click chemistry [1], multifunctional ligands were designed and synthesized for covalent conjugation of bone progenitor cells to particle-stabilized foams with defined pore structures [2]. This methodology resulted in enhanced and homogeneous colonization of biomaterials of different chemical composition (alumina, tricalcium phosphate and hydroxyapatite). Functionalization of these bioceramics with chemical ligands prefiguring click-reaction to cell surface proteins allowed concentration-dependent increase of both the number of adhered bone progenitor cells and their spreading within the matrix [3]. The methodology reported herein highlight the potential of chemically modified inorganic scaffold for bone implant development.
[1] Borcard, F.; Godinat, A.; Staedler, D.; Comas, H.; Dumont, A.-L.; Chapuis-Bernasconi, C.; Scaletta,C.; Applegate, L.A.; Krauss Juillerat, F.; Gonzenbach, U.T.; Gerber-Lemaire, S.; Juillerat- Jeanneret, L. J. Bioconjugate Chem., 2011, 22, 1422-1432. [2] Krauss Juillerat, F.; Gonzenbach, U.T.; Studart, A.R.; Gauckler, L. J. Mat. Lett. 2010, 64, 1468-1470. [3] Borcard, F.; Krauss Juillerat, F.; Staedler, D., Scaletta, C.; Applegate. L. A.; Comas, H.; Gauckler, L. J.,Gerber-Lemaire, S; Juillerat-Jeanneret, L.; Gonzenbach, U. T. Bioconjugate Chem., 2012, 23, 2278-2290.

Development of sequence-defined or structurally-precise polymers as high-performance materials is a major challenge in materials science. Recent advances in synthetic organic chemistry have provided increasing control over residue profile, chain length, and functional group placement, thereby facilitating the self-assembly of complex synthetic architectures. However, synthetic systems have yet to match the precise three-dimensional assembled architectures achieved by biologically derived polymers. Therefore, there is a strong need to broaden the capabilities of existing biopolymers to supplant “model” synthetic polymers for the production of advanced materials.
In this work, we report a facile synthesis platform to produce monodisperse and stereochemically precise nucleotidomimetic polymers. Based on a top-down approach, we are able to precisely incorporate a wide-variety of functional group modifications in a simple two-step process. First, we utilize the natural ability of DNA polymerase to enzymatically incorporate chemically-modified monomers (e.g., C5-dibenzocyclooctyl dUTP) in a template-directed fashion. Second, we employ copper-free click chemistry to integrate the desired chemical functionality at precise locations along the polymer chain. In this way, we produced a variety of branched DNA homopolymer architectures including 3-arm star, symmetric H, and block-brush. Overall, this synthetic strategy allows for the systematic variation of oligomer length, stoichiometry, concentration, and environmental conditions to rapidly explore nucleotidomimetic polymer phase behavior for materials discovery.

Discussed in this talk will be the development and advancement of trans-cyclooctene as a tool for facilitating bioorthogonal creation of macromolecular structure through reactions with s-tetrazines. While a number of strained alkenes have been shown to combine with tetrazines for applications in bioorthogonal labeling, trans-cyclooctene enables fastest reactivity at low concentration with rate constants in excess of k2 = 105 M-1s-1. Described will be advances in computation and synthesis that have enable application to materials science. Also described will be specific examples of using tetrazine-TCO ligation for surface patterining of expressed proteins, and for the synthesis and patterning of hydrogels for the in vitro culture of cells.

Precisely controlled structures and homologous series of model polymers are elusive when the architectures of interest involve bulky parts, and only become accessible when steric hindrance can be offset by highly active coupling chemistry. Two examples will be used to illustrate how macromolecules at the limits of the envelope of synthetically attainable structures achieve new functions and reveal surprising physics. The advent of robust coupling chemistries that provide essentially complete conversion without damaging essential functional groups (mild reaction conditions and orthogonal to other chemistries) have simplified and accelerated translation of molecular design to physical investigation of model polymers. In one example, precise end group functionalization of unusually long telechelic polymers provides a “drop in solution” for fire-safer fuel by combining two previously incompatible features—mist suppression and resistance to shear degradation. End-association of very long telechelics creates ultralong linear, flexible supramolecular chains the inhibit drop breakup; reversible dissociation into individual telechelics enables them to survive conditions that would cleave ultralong chains. The polymerization route to very long telechelics is incompatible with some of the key associative groups. Post-polymerization modification of chains having 10,000 repeat units (500kg/mol) must be achieved with high fidelity or the ultralong supramolecules will not form (monotelechelic chains act as caps that limit the length of supramolecules). The second example deals with bottlebrush polymers, molecules of intense interest for applications ranging from drug delivery to photonic structures. Theoretical predictions regarding the physics of bottlebrushes have outstripped the synthesis of molecules to test competing ideas. Ring-opening metathesis is a powerful methods to produce model bottle-brushes by “grafting through” macromonomers. Azide alkyne coupling enables high-yield, high-purity synthesis of macromonomers by coupling various side-chain structures to identical, polymerizable end groups. The resulting polymers have sidechains at every backbone repeat unit and have the same backbone structure across the set of model polymers. Thus, in the hands of non-expert chemists, click and ROMP have given access to model pairs of deuterium-labelled and hydrogenous bottlebrushes that clarify the random-walk character of the backbone, and pairs of neutral and polyelectrolyte polymers that expose the effects of electrostatic repulsion on the stretching of the backbone.

Chemical reactions fulfilling the click criteria[1, 2] are often promising candidates for applications in various scientific fields due to their high efficiency and facile handling. Herein, a range of ligation reactions, in particular radical and Michael type thiol-ene chemistry and the Diels-Alder reaction have been employed for fabrication and modification purposes in true 3D lithographic processes, specifically in direct laser writing (DLW).[3] In DLW, femtosecond pulses from a laser are focused into a photoresin. At the focal point insoluble polymer is generated for negative photoresins via two-photon induced photopolymerization. By moving the substrate accordingly, almost any 3D structure can be created. Whereas polymer generation proceeds via a chain polymerization mechanism in conventional DLW, a corresponding click chemistry approach proceeds via a step polymerization mechanism, opening an entirely new dimension to photoresin design.
As test structures for radical thiol-ene mediated DLW, we have fabricated woodpile photonic crystals with a footprint of 20 µm × 20 µm, a rod distance of 2 µm and a total number of 22 layers with a spacing of 700 nm for each consecutive layer. Via a subsequent thiol-Michael addition reaction, the surface of the fabricated structures can be covalently modified by reacting different functional maleimides with residual thiol units such as bromine- or fluorescein-containing maleimides.[4] Additionally, thiol-ene mediated DLW allows for the incorporation of new fabrication components such as functional polycarbonates for written structures. The resulting structures are then degradable under mild conditions and can be used, e.g., for lithographic inversion procedures.
Light-induced Diels-Alder processes can also be employed for DLW. By combining a tetrafunctional photoenol precursor molecule and a multiple maleimide containing polymer in one photoresin, we have fabricated highly resolved structures. Reactive dienes are generated in situ throughout the exposed polymerization volume, which subsequently react in a Diels-Alder reaction with the maleimide polymer, inducing crosslinked material. The Diels-Alder-based DLW allows for improved structural resolution in comparison to thiol-ene mediated DLW. The best we have achieved to date are woodpile photonic crystals with rod distances of 800 nm, a consecutive layer distance of 280 nm and a total of 10 layers.
[1] H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004-2021.
[2] C. Barner-Kowollik, F. E. Du Prez, P. Espeel, C. J. Hawker, T. Junkers, H. Schlaad, W. Van Camp, Angew. Chem. Int. Ed. 2011, 50, 60-62.
[3] S. Maruo, J. T. Fourkas, Laser & Photon. Rev. 2008, 2, 100-111.
[4] A. S. Quick, J. Fischer, B. Richter, T. Pauloehrl, V. Trouillet, M. Wegener, C. Barner-Kowollik, Macromol. Rapid Commun. 2013, 34, 335-340.

The reactivity features of thiolactones as functional handles for the synthesis and modification of various polymeric systems will be highlighted. The in situ generation of thiols by aminolysis of a thiolactone, followed by a UV-initiated radical thiolminus;ene reaction in a one-pot fashion, has been evaluated as an accelerated and versatile protocol for the synthesis of linear polymers and networks via a radical photopolymerization process (1). Recently, an additive free, nucleophilic amine-thiol-ene reaction cascade was employed as a extremely convenient one-pot method for the preparation of functionalized poly(urethanes) (2). Narrow polydisperse poly(thiolactones) have been synthesized via controlled copolymerization of functionalized vinyl monomers with a thiolactone containing monomer. Subsequently, a double modular modification (aminolysis and thiol-X) yields well-defined, multi-functional polymers (3, 4). Finally, an efficient synthetic pathway towards cylic polymers based on the combination of thiolactone and disulfide chemistry will be discussed (5).
(1) Espeel, P.; Goethals, F.; Du Prez, F.E. J. Am. Chem. Soc. 2011, 133 (6), 1678 - 1681.
(2) Espeel, P.; Goethals, F.; Driessen, F.; Nguyen, L.T.T.; Du Prez, F. E. Polym. Chem. 2013, 4, 2449-2456.
(3) Espeel, P.; Goethals, F.; Stamenovic, M. M.; Petton, L.; Du Prez, F. E. Polym. Chem. 2012, 3, 1007-1015.
(4) Reinicke, S.; Espeel, P.; Stamenovicacute;, M.M.; Du Prez, F.E. ACS Macro Letters 2013, 2, 539-543.
(5) Stamenovicacute;, M.M.; Espeel, P.; Baba, E.; Yamamoto, T.; Tezuka, Y.; Du Prez, F. E. Polym. Chem. 2013, 4, 184-193.

Radical addition of thiols to alkynes has been widely applied in polymer chemistry for the synthesis, functionalization and crosslinking of polymer networks. While both radical and nucleophilic thil-ene additions to carbon-carbon double bonds are well explored, the nucleophilic addition of thiols across triple bonds has received significantly less attention. We demonstrate that the base-catalyzed addition of alkyl thiols to electron-deficient alkynes with high levels of regioselectivity that can be directed based on the choice of catalyst and solvent (i.e. the polarity of the solvent mixture). Both thioalkenes and dithianes can be prepared in a rapid reaction that generates no by-products and thiol scrambling. In turn the utility of this reaction for efficient polymer material synthesis, functionalization and coupling is shown.

A better understanding of the physical and biomolecular cues in the stem cell niche has led to a growing interest in the development of material systems for improved 3D culture environments, as well as delivery vehicles to promote cell survival and differentiation. As a result, hydrogels based on both protein components (e.g., collagen and Matrigel) and highly-tunable synthetic chemistries (e.g., PEG) have evolved to address many of these needs. However, as advances in real-time tracking of dynamic cellular functions have emerged, complementary approaches to alter the surrounding extracellular environment in a user-defined and highly-controlled fashion are needed. Such materials systems have the potential to significantly improve our understanding of how cells receive information from their microenvironment and the role that these dynamic processes may play in biological questions related to their differentiation. Towards the goal of developing dynamically tunable scaffolds, this talk will highlight several approaches for in situ hydrogel property manipulation with light, allowing intimate control of a cell&’s microenvironment in both time and space. The synthesis and characterization of gels with photolabile linkers (e.g., nitrobenzyl ether) and photoconjugation reactions (e.g., thiol-ene) will be discussed, along with more recent developments in photoreversible reactions (e.g., addition fragmentation chain transfer reactions). These photoactive hydrogels afford unique user-defined manipulation of the biochemical and biomechanical nature of the extracellular microenvironment. This talk will present several examples where user-triggered changes in the material environment can be used to study study and direct human mesenchymcal stem cell function and by modifying the local hydrogel environment.

Spatiotemporal control over the formation of network cross-links afforded by photopolymerization is a strategy which has proven effective in the development of bioresponsive synthetic polymer hydrogels. This work describes a chemically modified recombinant protein polymer based upon the elastomeric structural protein, resilin, capable of photoinitiated thiol-ene cross-linking. This norbornene-functionalized resilin-like polypeptide (RLP) is cross-linked with a multi-arm PEG thiol to form a covalent network hydrogel. Equipped with a library of RLPs, which incorporate biological domains including MMP degradation sequences as well as cell adhesion sequences, these scaffolds may be adapted to a variety of tissue engineering applications. Expression and purification of the RLP is confirmed via SDS-PAGE and amino acid analysis. 1H-NMR spectroscopy confirmed the chemical modification lysine residues on the RLP with norbornene acid. Oscillatory photorheometry and tensile testing confirm that the mechanical properties of the hydrogels can be tuned upon photo-initiated cross-linking. This RLP-PEG hydrogel harnesses advantages of both synthetic and biosynthetic strategies for the development of hydrogel biomaterials.

Biomimetic materials - man-made materials inspired by natural processes and phenomena - have caught the attention of scientists in many research areas. Specifically, mimicking the adhesives used by maritime mussels to attach to virtually any surfaces are envisaged by us as the base for environmental friendly (photo-)click-able (bio)functional coatings for the attachment of any polymer chain or bioreceptor. In the current work, we fuse poly(dopamine) - a biomimetic polymer and highly versatile coating base - with advanced polymer chemistry able to provide the reversible attachment and detachment of polymer strands to surfaces. Our approaches include the preparation of tailor-made functional surfaces via mild thermally driven cycloaddition as well as photo-triggered reactions as a way to switchable universal surface chemistries and spatially functionalized surfaces for controlled cell adhesion. The described concept offers vast possibilities for the modification of surface properties on demand by both thermal and light triggered signals.
We prepared a dopamine-maleimide derivative which was, initially, conjugated (Diels-Alder reaction (DA)) with a cyclopentadiene-carrying PEG-chain and, secondly, attached to gold and other surfaces via an autopolymerization reaction of the compound itself under maritime conditions (Tris-buffer solution at pH = 8.5). Subsequently, several retro-DA (rDA) and DA sequences, where the PEG-chain was detached and re-attached, were executed on the surface. Thus, we generated a versatile DA-switching system, which possesses the ability to adhere to virtually any kind of surface in a biomimetic fashion and which permits engineering the surfaces chemistry and properties by the attachment and detachment of polymer chains on demand.
One of our most recent studies addresses controlled cell-adhesion on bio-inspired surfaces. In a grafting-from approach, polydopamine (PDA) surfaces were reacted with a photo-click-able group and a maleimide-carrying ATRP-Initiator was attached under UV irradiation. During the irradiation, parts of the surface were covered to achieve a regio-selective attachment of the initiator. In an ATRP-polymerization, MeOEGMA was grown from the surface. Subsequently, cell adhesion studies evidenced the attachment of the cells only in regions where no polymer had been grafted. Thus, we prepared a regio-selective photo-click-system to grow polymer chains in specific areas, which allows controlled and defined cell adhesion.

Short peptides N-protected with hydrophobic moieties have been repeatedly demonstrated to self-assemble into nanofibrillar structures to form gels within aqueous environments upon triggering by a change in pH, temperature, or addition of salts. This mild gelation process makes these materials ideal candidates for injectable biomaterials, and, as the substituents are short peptides of low molecular weight, these materials are potentially bioactive and amenable to renal clearance. However, as these materials are peptide-based, their in situ degradability is likely determined by the protease content of the particular tissue in which they might be injected; peptide bonds are resistant to non-enzyme mediated hydrolysis over the weeks-to-months time scale of wound healing and tissue regeneration. For this reason, our group has sought to develop similar self-assembling materials from depsipeptides, which contain ester substitutions in the backbone. Esters are much more susceptible to hydrolysis than are peptide bonds, and therefore ester-containing materials are able to degrade without the need for tissue specific protease enzymes.
Depsipeptides are synthesized by substituting into synthetic peptides alpha-hydroxy acids with side chain groups identical to those of natural amino acids. Our group recently published a general method for synthesizing di-depsipeptide units that could be further reacted on solid phase using standard solid phase peptide synthesis chemistries. We also found that the di-depsipeptide analog of a simple dipeptide conjugate hydrogelator was also able to form a hydrogel with similar morphological properties. Longer, zwitterionic depsipeptide conjugates were also able to self-assemble into hydrogels. With these results suggesting that the ester substitution may not disrupt the self-assembly process, we focused next on synthesizing a depsipeptide analog of the cell-binding motif, Arginine-Glycine-Aspartic acid (RGD), to investigate the effects of the ester substitution on an important and well-characterized protein-ligand system.
In this work, we describe the synthesis of fluorenxylmethoxycarbonyl (Fmoc)-protected R-Glc-D and several variants with additional residues or alternate hydrophobic N-terminal groups, all of which have the glycolic acid (Glc)-containing sequence analogous to RGD. We demonstrate the conditions under which each variant is able to self-assemble into a hydrogel, and we characterize the degradation rate of the molecules relative to that of the native peptide conjugate, Fmoc-RGD, both in solution and in gel form at physiological temperature. Finally, we show the results of integrin binding assays based on surface plasmon resonance (SPR), in order to compare the integrin binding ability of R-Glc-D variants relative to Fmoc-RGD. Future work will include in vitro studies to quantify any reduction or increase in cell binding to R-Glc-D variants, as well as cytotoxicity and cell proliferation studies.

Although the primary focus to enhance transgene expression in vivo has been the design of the delivery vector, the matrix itself can provide alternative approaches to enhance transfection efficiency as well as promote tissue formation. However, it first needs to be recognized that gene transfer to cells seeded in a three dimensional environment occurs through different mechanisms to cells seeded in a two dimensional environment. Utilizing synthetic hydrogel scaffolds as in vitro gene transfer platforms we were able to elucidate significant differences in the mechanism of gene transfer when cells are seeded inside hydrogel scaffolds than when they are seeded on tissue culture plastic, the traditional surface used to assess the efficiency of gene transfection vectors.

Successful islet transplantation has the potential to cure type 1 diabetes. However, unprotected islet grafts are prone to immune rejection, which leads to the eventual failure of the grafts. To this end, various immunoisolation barriers have been proposed for islet encapsulation to prolong the survival and function of the transplanted islets. We have recently developed a visible light mediated interfacial thiol-ene reaction to form multilayer hydrogels. In this highly efficient visible light photocrosslinking reaction, eosin-Y is used as the single initiator. Using a similar coating technique, we have successfully prepared conformal coating on the surface of beta-cell aggregates and isolated islets. Multi-arm poly(ethylene glycol) norbornene (PEGNB) and dithiol-containing molecules (e.g., dithiothreitol) were used for forming an idealized hydrogel network. Owing to the highly controllable thiol-ene reactions, thickness of the gel coating could be readily tuned via controlling light exposure time and macromer compositions. This unique and simple photochemistry also overcomes major shortcomings associated with prior conformal coating technique using visible light-mediated chain-growth polymerization. First, rapid thiol-ene gelation is maintained without the use of cytotoxic co-initiator (TEOA) or co-monomer (NVP). Second, this reaction is more cytocompatible than the conventional PEG diacrylate (PEGDA) conformal coating. Finally, the step-growth thiol-ene network provides an idealized and homogeneous structure that does not hinder insulin transport. Compared to unprotected islets, the thiol-ene coated islets successfully suppressed high glucose levels in diabetic NOD/scid mice. The thiol-ene conformal gel coating serves as a biomimetic culture platform to preserve the viability of artificial or isolated islets and prevent them from losing islet cell characteristics. Additionally, various photo-conjugation techniques for functionalizing PEG gels are compatible with the thiol-ene reactions for creating biomimetic coating.

Synthetic analogs of the extracellular microenvironment pose as an attractive platform to elucidate complex cellular interactions and potentially guide cellular responses. Although such systems reported thus far are often oversimplified, substantial insight on the effect of extrinsic cues originating from the extracellular matrix, soluble factors, or neighboring cells are paving the way towards directing cell fate. In particular, geometric cues, such as patterns in both the nanoscale and microscale regime, have been demonstrated as a powerful tool to elicit different responses ranging from cell adhesion, migration, differentiation, and morphology. Moreover, hierarchical patterns are emerging as a route to study cell behavior. Approaches that have been pursued for hierarchical patterning of biomolecules include block copolymer (BCP) micelle lithography coupled with photo- or electron-beam lithography, scanning probe BCP lithography, and specialized microfabrication techniques. However, techniques based on BCP micelle lithography are limited to inorganic dot arrays and specialized microfabrication techniques entail expensive equipment and expertise not readily available by many groups. Here, we present a high-throughput method for achieving hierarchical patterns of biomolecules through the self-assembly of a functionalized BCPs coupled with photolithography. The system is based on a BCP of poly(ethylene oxide) end-functionalized with biotin and poly(styrene-co-4-bromostyrene) where the addition of 4-bromostyrene serves as a cross-linking unit upon UV irradiation. Through facile processing, hierarchical patterns were observed by optical microscopy, where post-biofunctionalization was demonstrated through the ubiquitous biotin-streptavidin handle. Two morphologies—lines and dots of biomolecules, are readily accessed with the single BCP by simply altering annealing conditions. Moreover, mixed morphologies on a single substrate may be obtained, where a combination of dots, lines, as an as-cast morphology is achieved by modifying irradiation dose and the order of processing steps. These substrates serve as a straightforward material for investigating the effects of hierarchical patterning of biomolecules on mesenchymal stem cell differentiation.

Research in both the physical and biological sciences chronically suffers from the low productivity and reproducibility of experimental studies. This is due in part because the traditional text-based format of science journals cannot provide an adequate description of complex research procedures. This creates a critical “bottleneck” problem of knowledge transfer for research and education. Addressing this challenge, a new generation of science journals employs online video to provide a systematic visualized publication of experimental studies. This presentation will provide an overview of the growing field of video publication and discuss its technical challenges, implications for scholarly communication and acceptance in the academic and library community. Results and recently conducted case studies will be shown in support of video publications as a valid communication venue in scientific publishing.

Polymerized ionic liquids (PILs) are unique polyelectrolytes with cationic and anionic groups included in the repeating unit. They are extremely attractive in the field of materials science as they combine the properties of ionic liquids (high ionic conductivity, thermal and chemical stabilities) with those of polymers (mechanical stability, processing and tunable macromolecular design). Many examples have demonstrated their potential in applications such as dye sensitized solar cells, fuel cells, batteries, permselective membranes for CO2 recovery or catalysis. In all these applications, imidazolium-based PILs are by far the most widespread and investigated materials. Since the striking development of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) modular ligation, a large variety of materials containing 1,2,3-triazole groups have been reported. However, applications of 1,2,3-triazoliums as anion recognition structures, organocatalysts, metal ligands and precursors of N-heterocyclic carbenes has only been explored lately. We have recently pioneered the synthesis of 1,2,3-triazolium-based PILs. The tuning of structural parameters has a tremendous effect on ionic conductivity and thermal stability, crucial properties in most applications of PILs. The first generation TPILs not only demonstrates ionic conduction similar to that of PILs with comparable structure, pendant substituent and anion, but their synthesis also benefits from the robust and orthogonal nature of CuAAC. This oral communication is an attempt to demonstrate the potential of 1,2,3-triazolium chemistry to tackle new synthetic challenges using unexplored approaches competent to broaden the current structural variety of PILs.

Poly(propargyl-L-glutamate) (PPLG) has recently been developed as an N-carboxy anhidride polymerized polypeptide with high grafting efficiency, a wide range of available functional groups, and ability to incorporate into hydrogels with tunable mechanical properties. PPLG is thus an attractive macromere for a range of biological material applications, particularly in creation of smart hydrogels. A wide variety of functional groups can be grafted to the PPLG alpha helical backbone through copper-catalyzed 1,3-cycloaddition reaction between the polymer alkyne and an azide. A previously published synthesis of PPLG hydrogels established Michael-type addition crosslinking of thiol terminated poly(ethylene glycol) (PEG) and maleimide grafted PPLG. However, this published approach grafted maleimide to the PPLG via non-specific in situ crosslinking, incompatible with grafting of peptides and proteins, and crosslinked the gels in DMSO, incompatible with cell encapsulation. Here, we introduce a new approach to PPLG hydrogels based on forming PPLG macromonomers pre-grafted with one of two orthogonal chemistries, maleimides and norbornenes. Functionalized PPLG was incorporated with PEG-thiols to form hydrogels using protocols suitable for cell encapsulation and capable of incorporating bioactive proteins. We grafted PPLG macromolecules with a degree of polymerization greater than 50 with short ethylene glycol side chains, and between 1 and 10 crosslinking maleimide or norbornene-terminated PEG crosslinkers per PPLG molecule. The grafted PPLG was then crosslinked with 4 arm PEG thiol to form a stable hydrogel. In solution phase and in the crosslinked hydrogel, degradation studies indicate slow hydrolysis of the PPLG ester side groups at pH 7.4. Swelling and mechanical properties of PPLG-PEG hydrogels demonstrate a strong dependence of bulk hydrogel properties on the average number of crosslinking sidechains on each PPLG polymer. Finally, the biocompatibility of this modified PPLG hydrogel system was demonstrated in both 2D and 3D cell culture.

A highly reliable and practical reaction, click reaction was employed as a coupling protocol which was structurally integrated into reactive energetic plasticizers (REP) for use in glycidyl azido polymer (GAP) based energetic polyurethane (PU) binders. Two classes of REPs with either ether linkage or ester linkage adjacent to terminal alkyne group as well as nitro group were successfully synthesized and characterized by 1H NMR and 13C NMR. REPs are believed to improve the processibility of GAP-based formulation system and complete the chemical incorporation with GAP-based polymer matrix via Cu-free click reaction during curing process. Plasticization effect of those structurally diversified REPs on uncured GAP prepolymer were evaluated by viscosity and glass transition temperature (Tg). Both activation energy (Ea) measured by differential scanning calorimetry (DSC) and click reaction in bulk condition evaluated by 1H NMR between REP and GAP were simultaneously verified that clickable reactivities of REPs were controllable by altering the distance between electron-withdrawing group (EWG) and terminal alkyne. This was attributed to EWG adjacent to alkyne could accelerate the click reaction due to the decrease of energy level between LUMO of alkyne and HOMO of azide by utilizing EWG to decrease the electron density of alkyne which could be directly observable from 1H NMR of pure REPs. Mechanical properties and thermal stabilities of REPs incorporated GAP-based polyurethanes (PUs) binders were also studied.

This talk will describe our efforts to apply efficient organic transformations in the context of polymer network synthesis to ultimately yield novel functional materials. In particular, new concepts for preparation of materials that report their network connectivity, including dangling chain and loop fractions, will be discussed. These concepts rely on orthogonal, efficient network formation (click) and disassembly (clip) reactions.

Functional materials are predicted to have an enormous impact on many aspects of society, including next generation health care and energy-related technologies. Bottom-up approaches, using self-assembly principles, are increasingly considered to be the most appropriate routes for their synthesis. Almost all self-assembled structures obtained by mixing molecules were realized in solution. Molecular architectures that spontaneously grow exclusively near a surface are rare. Inspiration often comes from the biological world where many outstanding examples of highly complex functional nanoscale architectures have been discovered. Self-organizations resulting in complex biological tissue morphologies are driven by morphogens gradients, specific molecules to which cells respond in a concentration dependent manner.
Recently, we extended this definition to self-constructing films, whose buildups are triggered by the presence of ions, the morphogens, generated at the substrate. The electro-triggered film construction is obtained through the formation of covalent bonds between polymers present simultaneously in solution. This was done by using the Huisgens "click" reaction catalyzed by Cu(I) ions. We used two polymers bearing complementary groups, one with azide and the other with alkyne groups grafted onto their backbone. The Cu(I) ions, which play here the role of morphogens, are produced electrochemically in a continuous way through cyclic voltammetry by reduction of Cu(II) ions present in the solution. The Cu(I) ions then diffuse from the surface to the solution and catalyze the click reaction leading to the formation of triazoles by reaction between the azides and the alkynes. Because the reaction between the azides and alkynes takes only place in the presence of Cu(I) generated exclusively at the substrate, one can mix all the constituent protagonists (polymer-azide, polymer-alkyne, Cu(II)) in a single solution and induce the film formation by the simple application of a reduction potential through cyclic voltammetry, to form the morphogen. The one-pot morphogen film buildup was applied to polycationic, polyanionic and neutral polymer systems. Films whose integrity relies on host-guest interactions were also developed using clickable cyclodextrins and ferrocenes in combination with an azide-bearing PAA.

The attractiveness of conjugated polymers (CPs) as highly processable semiconducting materials for light-emitting, solar energy harvesting, and electronic applications largely stems from their solution processibility. This property allows for easy spin-coating, spraying, and inking of films directly onto a variety of rigid and flexible substrates. However, the same ease of solution processing leads to difficulties in building multilayer and patterned devices, which can greatly improve device performance. Covalent cross-linking of CP films offers one solution to this problem. By making the semiconducting layers robust and solvent-resistant after processing, a path is opened for more complicated fabrication processing. Additionally, the “locking” of polymer chains into position has been shown to improve certain electronic characteristics by significantly reducing their tendency to re-align during device operation. Cross-linking also enables the incorporation of a wide range of chemical functionality that can be imbedded in the polymer during curing. In recent work, we aim to investigate thiol-ene cross-linked CPs. Thiol-ene click chemistry has grown tremendously in popularity over the past few years and has been shown to possess numerous processing advantages such as rapid reaction rates, minimal oxygen inhibition, and high reaction yields in direct contrast to the required high temperatures, long reaction times, and oxygen-free environments needed for the thermal initiation of 4-phenylethenyl cross-linking groups previously popular with CPs. UV-initiated thiol-ene chemistry also requires no added initiator, mitigating potential issues with residual photo-acid and photo-radical generators used in the UV-initiated cross-linking of oxetane and acrylate functionalized CPs. Furthermore, thiol-ene chemistry is well-suited to lithographic patterning.

Designing conjugated polymers (CPs) conventionally takes place either at the fundamental synthetic level where targeted chemical synthesis anticipates electronic function, or at the supramolecular level where control over the architecture can impact bulk properties. Post-chemical modifications directly to the CP are avoided due to uncontrolled reactivity under harsh conditions required in several reactions, however, they are possible. Exploiting robust, efficient, and orthogonal chemistry to change the electronic properties of macromolecules having well-defined architecture and chemical functionality broadens the scope of CPs in modern technological applications. This talk describes a method to change the band gap of thiophene-containing CPs based on the use of hypofluorous acid (HOF), an unprecedentedly fierce, yet selective oxidizing agent.