Vinylogous Urea-Urethane Vitrimers: Accelerating and Inhibiting Network Dynamics through Hydrogen Bonding.

Vinylogous urethane (VUO ) based polymer networks are widely used as catalyst-free vitrimers that show rapid covalent bond exchange at elevated temperatures. In solution, vinylogous ureas (VUN ) undergo much faster bond exchange than VUO and are highly dynamic at room temperature. However, this difference in reactivity is not observed in their respective dynamic polymer networks, as VUO and VUN vitrimers prepared herein with very similar macromolecular architectures show comparable stress relaxation and creep behavior. However, by using mixtures of VUO and VUN linkages within the same network, the dynamic reactions can be accelerated by an order of magnitude. The results can be rationalized by the effect of intermolecular hydrogen bonding, which is absent in VUO vitrimers, but is very pronounced for vinylogous urea moieties. At low concentrations of VUN , these hydrogen bonds act as catalysts for covalent bond exchange, while at high concentration, they provide a pervasive vinylogous urea - urethane (VU) network of strong non-covalent interactions, giving rise to phase separation and inhibiting polymer chain dynamics. This offers a straightforward design principle for dynamic polymer materials, showing at the same time the possible additive and synergistic effects of supramolecular and dynamic covalent polymer networks.

Resorcinol-Derived Vitrimers and Their Flax Fiber-Reinforced Composites Based on Fast Siloxane Exchange.

Natural fiber-reinforced composites are gaining increased interest for their significantly reduced carbon footprint compared to conventional glass or carbon fiber-based counterparts. In this study, natural fibers are used in a resorcinol-based epoxy resin that is thermally reshapable at higher temperatures (>180 °C) by using fast exchanging siloxane bonds, catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene. Stress relaxation times of only about 6 s at 220 °C can be reached. A resorcinol-based epoxy compound is selected because it can be derived from cellulose, opening ways for more sustainable and reshapable composite materials. In a last step of the research, the low viscosity vitrimer formulation (<200 mPa s) is applied to make a flax fiber-reinforced composite using an industrially relevant vacuum-assisted resin infusion process. A section of this composite is successfully reshaped, which allows for envisioning a second life for natural fiber-reinforced composites.

The Power of Action Plots: Unveiling Reaction Selectivity of Light-Stabilized Dynamic Covalent Chemistry.

Exploiting the optimum wavelength of reactivity for efficient photochemical reactions has been well-established based on the development of photochemical action plots. We herein demonstrate the power of such action plots by a remarkable example of the wavelength-resolved photochemistry of two triazolinedione (TAD) substrates, i.e., aliphatic and aromatic substituted, that exhibit near identical absorption spectra yet possess vastly disparate photoreactivity. We present our findings in carefully recorded action plots, from which reaction selectivity is identified. The profound difference in photoreactivity is exploited by designing a 'hybrid' bisfunctional TAD molecule, enabling the formation of a dual-gated reaction manifold that demonstrates the exceptional and site-selective (photo)chemical behavior of both TAD substrates within a single small molecule.

Visible Light Conjugation with Triazolinediones as a Route to Degradable Poly(ethylene glycol)-Lipids for mRNA Lipid Nanoparticle Formulation.

Polyethylene glycol (PEG) is considered as the gold standard for colloidal stabilization of nanomedicines, yet PEG is non-degradable and lacks functionality on the backbone. Herein, we introduce concomitantly PEG backbone functionality and degradability via a one-step modification with 1,2,4-triazoline-3,5-diones (TAD) under green light. The TAD-PEG conjugates are degradable in aqueous medium under physiological conditions, with the rate of hydrolysis depending on pH and temperature. Subsequently, a PEG-lipid is modified with TAD-derivatives and successfully used for messenger RNA (mRNA) lipid nanoparticle (LNP) delivery, thereby improving mRNA transfection efficiency on multiple cell cultures in vitro. In vivo, in mice, mRNA LNP formulation exhibited a similar tissue distribution as common LNPs, with a slight decrease in transfection efficiency. Our findings pave the road towards the design of degradable, backbone-functionalized PEG for applications in nanomedicine and beyond.

Reading Information Stored in Synthetic Macromolecules.

The storage of information in synthetic (macro)molecules provides an attractive alternative for current archival storage media, and the advancements made within this area have prompted the investigation of such molecules for numerous other applications (e.g., anti-counterfeiting tags, steganography). While different strategies have been described for storing information at the molecular level, this Perspective aims to provide a critical overview of the most prominent approaches that can be utilized for retrieving the encoded information. The major part will focus on the sequence determination of synthetic macromolecules, wherein information is stored by the precise arrangement of constituting monomers, with an emphasis on chemically aided strategies, (tandem) mass spectrometry, and nanopore sensing. In addition, recent progress in utilizing (mixtures of) small molecules for information storage will be discussed. Finally, the closing remarks aim to highlight which strategy we believe is the most suitable for a series of specific applications, and will also touch upon the future research avenues that can be pursued for reading (macro)molecular information.

Reversible Transformations of Polymer Topologies through Visible Light and Darkness.

A fundamentally important characteristic of a macromolecule is its shape. Herein, visible light and darkness are used as the only stimuli to reversibly alter the topology of well-defined polymers in a one-pot procedure. For this, linear naphthalene-containing polyacrylates are used as scaffolds for the visible light-induced cycloaddition with various substituted triazolinediones (i.e., butyl, stearyl, perfluoro, and polymeric), resulting in differently shaped graft polymers, including brushes and combs. The thus-formed cycloadduct linkages dissociate in the dark, resulting in the regeneration of the parent linear polymer at ambient temperature, establishing a dual-topology transformation by only switching green light on and off. By applying different temperatures during the cycloreversion process, the dissociation rate of the cycloadducts can be tuned in a facile manner, thus allowing for time control over the regeneration of the parent polymer. By engineering a polymer that consists of differently substituted naphthalenes at the chain ends and on the side chains, the inherently different cycloreversion rates of the formed cycloadducts are leveraged to achieve in situ multi-topology transformations without external stimuli. The shape transformations have been repeated up to 4 times sequentially in one pot without the need of any purification. The topological alterations are microscopically depicted through reversible self-assembly, with the polymers adopting different morphologies upon visible light or darkness. The versatile yet practical nature of this polymer "reshaping" strategy provides facile access to multifaceted polymer systems and, consequently, to a plethora of potential applications thereof.

Sequence-Defined Mikto-Arm Star-Shaped Macromolecules.

The synthesis of sequence-defined, discrete star-shaped macromolecules is a major challenge due to the lack of straightforward and versatile approaches. Here, a robust strategy is proposed that allows not only the preparation of sequence-defined mikto-arm star-shaped macromolecules but also the synthesis of a series of unprecedented discrete, multifunctional complex architectures with molar masses above 11 kDa. The iterative approach reported makes use of readily available building blocks and results in asymmetrically branched macromolecules with high purity and yields, which is showcased with monodisperse mikto-arm three-, four-, and five-arm star-shaped structures that were all characterized via LC-MS, MALDI-ToF, and NMR. This effective strategy drastically improves upon synthetic abilities of polymer chemists by enabling simultaneously sequence definition, precision insertion of branching points, as well as the orthogonal end-group functionalization of complex polymeric architectures. The presented approach, which can be translated to different platforms such as peptides and peptoids, is therefore particularly interesting in biomedical applications for which multiple different functional moieties on a single discrete macromolecule are needed.

Fast Dynamic Siloxane Exchange Mechanism for Reshapable Vitrimer Composites.

To develop siloxane-containing vitrimers with fast dynamic characteristics, different mechanistic pathways have been investigated using a range of catalysts. In particular, one siloxane exchange pathway has been found to show a fast dynamic behavior in a useful temperature range (180-220 °C) for its application in vitrimers. The mechanism is found to involve 1,5,7-triazabicyclo [4.4.0] dec-5-ene (TBD) as an organic catalyst in the presence of hydroxyl groups. Using this new mechanistic approach, vitrimers with ultrafast stress-relaxation characteristics (relaxation times below 10 s) have been prepared with a readily available epoxy resin and siloxane-amine hardener. Subsequently, the low viscosity siloxane-containing vitrimer resin enabled the preparation of glass fiber-reinforced vitrimer composites using an industrially relevant vacuum-assisted resin infusion technique. The resulting composite was successfully thermoformed into a new shape, which makes it possible to envision a second life for such highly engineered materials.

Sequencing of Uniform Multifunctional Oligoesters via Random Chain Cleavages.

Sequence-defined polymers have been the object of many fascinating studies that focus on their implementation in both material and life science applications. In parallel, iterative synthetic methodologies have become more efficient, whereas the structure elucidation of these molecules is generally dependent on MS/MS analysis. Here, we report an alternative, simple strategy for the determination of the monomer order of uniform oligo(thioether ester)s. This approach, which relies on random cleavages of ester units within the macromolecular backbone via a basic treatment, enables the swift characterization of these macromolecules without the need for MS/MS. Consequently, this method can be used for decoding any information stored within the primary structure of oligoesters by means of ESI- or LC-MS. Finally, we speculate that a range of structurally diverse backbones could be susceptible towards this approach, which could promptly expand the library of chemically sequenceable macromolecules.

Rewritable Macromolecular Data Storage with Automated Read-out.

Rewriting data stored on synthetic macromolecules is an interesting feature, even though it is considered as being quite challenging within the area of digital macromolecules. In this context, we initially studied a strategy for modifying the position tag of sequence-encoded macromolecules in a reversible manner. The efficiency of this method, which relies on the orthogonal cleavage of a thioester moiety via aminolysis, was demonstrated by modifying parts of an exemplary sentence. Simultaneously, a novel algorithm was developed to ease the read-out of macromolecular information by means of MS/MS techniques. This program, Oligoreader, can identify potential information-containing macromolecules from a series of MS1 spectra, analyze the corresponding MS2 spectra, and finally decode the data. Consequently, the algorithm simplifies the entire read-out process by avoiding any interference from the operator, which increases the potential for blind sequencing of uniform macromolecules.

A Highly Dynamic Covalent Polymer Network without Creep: Mission Impossible?

Dynamic covalent polymer networks provide an interesting solution to the challenging recyclability of thermosets and elastomers. One of the remaining design constraints, however, is balancing thermal reprocessability in the form of material flow with dimensional stability during use. As a result, many chemistries are being investigated in order to improve bond reactivity control and material robustness. This Minireview highlights a number of promising concepts, with a particular emphasis on disconnecting chemical reactivity in low and high temperature regimes to obtain creep resistant, yet highly dynamic polymer networks. In addition, we will highlight the impact of sharp reactivity changes when applying extrapolation-based approaches during rheological analysis. As a result, we are confident that abandoning the myth of "permanent" reactivity will aid in the development of sustainable polymeric materials that can truly combine the benefits of thermoplastic and thermoset behaviour.

Suppressing Creep and Promoting Fast Reprocessing of Vitrimers with Reversibly Trapped Amines.

We report a straightforward chemical strategy to tackle current challenges of irreversible deformation in low Tg vitrimers at operating temperature. In particular, vinylogous urethane (VU) vitrimers were prepared where reactive free amines, necessary for material flow, were temporarily shielded inside the network backbone, by adding a small amount of dibasic ester to the curing mixture. The amines could be released as reactive chain ends from the resulting dicarboxamide bonds via thermally reversible cyclisation to an imide moiety. Indeed, (re)generation of the required nucleophilic amines as network defects ensured reprocessing and rapid material flow at higher temperature, where exchange dynamics are (re)activated. As a result, VU vitrimers were obtained with limited creep at service temperature, yet with good reprocessability at elevated temperatures. Thus, by exerting strong control on the molecular level over the availability of exchangeable functional groups, a remarkable improvement of VU properties was obtained.

Covalent Adaptable Networks Using ß-Amino Esters as Thermally Reversible Building Blocks.

In this study, ß-amino esters, prepared by the aza-Michael addition of an amine to an acrylate moiety, are investigated as building blocks for the formation of dynamic covalent networks. While such amino esters are usually considered as thermally nondynamic adducts, the kinetic model studies presented here show that dynamic covalent exchange occurs via both dynamic aza-Michael reaction and catalyst-free transesterification. This knowledge is transferred to create ß-amino ester-based covalent adaptable networks (CANs) with coexisting dissociative and associative covalent dynamic exchange reactions. The ease, robustness, and versatility of this chemistry are demonstrated by using a variety of readily available multifunctional acrylates and amines. The presented CANs are reprocessed via either a dynamic aza-Michael reaction or a catalyst-free transesterification in the presence of hydroxyl moieties. This results in reprocessable, densely cross-linked materials with a glass transition temperature (Tg) ranging from -60 to 90 °C. Moreover, even for the low Tg materials, a high creep resistance was demonstrated at elevated temperatures up to 80 °C. When additional ß-hydroxyl group-containing building blocks are applied during the network design, an enhanced neighboring group participation effect allows reprocessing of materials up to 10 times at 150 °C within 30 min while maintaining their material properties.

Reprocessing of Covalent Adaptable Polyamide Networks through Internal Catalysis and Ring-Size Effects.

Here, we report the introduction of internally catalyzed amide bonds to obtain covalent adaptable polyamide networks that rely on the dissociation equilibrium between dicarboxamides and imides. While amide bonds are usually considered to be robust and thermally stable, the present study shows that their dynamic character can be activated by a smart choice of available building blocks without the addition of any external catalyst or other additives. Hence, a range of polyamide-based dynamic networks with variable mechanical and viscoelastic properties have been obtained in a systematic study, using a straightforward curing process of dibasic ester and amine compounds. Since the dissociation process involves a cyclic imide formation, the correlation between ring size and the thermomechanical viscosity profile was studied for five- to seven-membered ring intermediates, depending on the chosen dibasic ester monomer. This resulted in a marked temperature response with activation energies in the range of 116-197 kJ mol-1, yielding a sharp transition between elastic and viscous behavior. Moreover, the ease and versatility of this chemistry platform were demonstrated by selecting a variety of amines, resulting in densely cross-linked dynamic networks with Tg values ranging from -20 to 110 °C. With this approach, it is possible to design amorphous polyamide networks with an acute temperature response, allowing for good reprocessability and, simultaneously, high resistance to irreversible deformation at elevated temperatures.

Surface Modification of (Non)-Fluorinated Vitrimers through Dynamic Transamination.

Surface modifications are typically permanent in shape and chemistry. Herein, vinylogous urethane (VU) chemistry is presented as an easily accessible and versatile platform for rapid, facile, and reworkable surface modification. It is demonstrated that both physical and chemical post-modification of permanent, yet dynamic elastic polymer networks are achieved. Surface patterns with high regularity are created, both via a straightforward replication process using a polydimethylsiloxane stamp (resolution ca. 10-100 µm) as well as using thermally activated nano-imprint lithography (NIL) to form hole, pillar, or line patterns (ca. 300 nm) in elastic VU-based vitrimers. The tunable, rapid exchange allows patterning at 130 °C in less than 15 min, resulting in an increased water contact angle and surface-structure induced light reflection. Moreover, it is also demonstrated that the use of a single dynamic covalent chemistry makes it possible to strongly adhere to fluorinated and non-fluorinated materials based on incompatible matrices, causing cohesive failure in a peel test. In a topography scan, the visibly transparent interface is shown to possess a continuous phase without a gap, while maintaining distinctively separated (non)-fluorinated domains. Finally, this approach allowed for a straightforward coating of a non-fluorinated material with a fluorinated monomer to minimize the overall fluorinated content.

Substituent effect on the thermophysical properties and thermal dissociation behaviour of 9-substituted anthracene derivatives.

The chemical structure and location of substituents on anthracene derivatives influence the electron balance of the aromatic system, thus determining the wavelengths at which light is absorbed, which results in the photochemically induced dimerization or monomerization. Here, the thermal dissociation kinetics of 7 photodimers of 9-substituted anthracene derivatives are studied using a combination of spectroscopic and calorimetric techniques in the condensed state and compared to scarce literature data on thermal dissociation of other anthracene derivatives. The length and chemical structure of the substituent chains have a clear impact on the melting temperatures of the anthracene derivatives and corresponding photodimers. The crystallinity of the photodimers and monomers in turn influences the thermal dissociation kinetics. The thermal dissociation behaviour and previously published photochemistry data are related to the electronic effects of the substituents by means of the Hammett parameters. Stronger electron-withdrawing effects result in larger red shifts of the maximum wavelength λmax for the photodimerization of the anthracene derivatives. It is also shown that for the studied substitutions on the 9-position of anthracene, the higher the magnitude of the electronic effect - both electron-donating and electron-withdrawing - the faster the thermal dissociation kinetics and thus the lower the thermal stability. The strong electronic effects of the substituents on the thermal and photochemical reactivity of the anthracene derivatives and their photodimers allow tuning of the thermal or photochemical responsiveness, e.g. for polymer networks.

Internal catalysis for dynamic covalent chemistry applications and polymer science.

Strong covalent chemical bonds that can also be reversed, cleaved or exchanged are the subject of so-called dynamic covalent chemistry (DCC). Applications range from classical protective groups in organic chemistry and cleavable linkers for solid phase synthesis, to more modern applications in dynamic compound libraries and adaptive materials. Interest in dynamic, reversible or responsive chemistries has risen in particular in the last few decades for the design and synthesis of new DCC-based polymer materials. Implementation of DCC in polymers yields materials with unique combinations of properties and in some cases even unprecedented properties for covalent materials, such as self-healing materials, covalent adaptable networks (CANs) and vitrimers. In particular, the incorporation of DCC in polymer materials aims to find a balance between a swift and triggerable reactivity, combined with a high degree of intrinsic robustness and stability. Applying harsh conditions, highly active catalysts or highly reactive bonding groups, as is done in classical DCC, is often not feasible or desirable, as it can damage the polymer's integrity, leading to loss of function and properties. In this context, so-called internally catalysed DCC platforms have started to receive more interest in this area. This approach relies on the relative proximity and orientation of common functional groups, which can influence a chemical exchange reaction in a subtle but significant way. This approach mimicks the strategies found in enzymic reactions, and is known in classical organic chemistry as neighbouring group participation (NGP). The use of internal catalysis or NGP within polymer material science has proven to be a highly attractive strategy. This tutorial review will outline examples showing the scope, advantages and pitfalls of using internal catalysis within different DCC applications, ranging from small molecules to dynamic polymer materials.

On-Demand Dissoluble Diselenide-Containing Hydrogel.

On-demand dissolution of hydrogels is being increasingly studied for their potential use in burn wound dressing applications. Herein, a dynamic diselenide-containing hydrogel is developed through a very simple one-pot and two-step process starting from the selenol functionalization of a partially hydrolyzed poly(2-ethyl-2-oxazoline) with γ-butyroselenolactone. The hydrogel spontaneously cross-links via an in situ oxidation of the selenol functionalities in air. The gelation process and the final viscoelastic properties of the gel are characterized by rheological experiments. The mechanical properties of those new diselenide-containing hydrogels are easily tuned by varying the concentration of γ-butyroselenolactone. The materials also show good skin adhesion and UV light responsiveness. A unique feature of the hydrogel is its capability to be fully and rapidly dissolved on-demand, via oxidation or reduction of the diselenide cross-links, making them particularly attractive for burn wound dressing applications.

Thermal dissociation of anthracene photodimers in the condensed state: kinetic evaluation and complex phase behaviour.

Thermally and photochemically reversible functional groups, such as photodimers of anthracene derivatives, offer interesting stimuli-responsive behaviour. To evaluate their potential for application in reversible polymer networks, accurate kinetic parameters and knowledge of their thermophysical behaviour are required. Accurate kinetic studies of the thermal dissociation of the photodimers in the condensed state, thus without the influence of solvents on their reactivity, is still lacking. A methodology was set up to accurately evaluate the chemical reaction kinetics and complex phase behaviour during the thermal dissociation of photodimers into their corresponding monomers. Temperature-controlled time-resolved FTIR spectroscopy was used to determine the reaction progress, while non-isothermal DSC measurements were used to study the thermophysical changes, resulting from the thermal dissociation reaction. The thermal dissociation behaviour in the condensed state is more challenging than in the solution state due to the crystallinity of the dimers, stabilizing the dimers and thus slowing down the initial dissociation rates. Distinctly different sets of kinetic parameters were found for the dissociation from the molten and the crystalline state. For experiments performed below the melting temperature of the photodimer, the reaction rate changes abruptly as the dimer is partly dissociated and partly dissolved into the formed monomer. This methodology provides an accurate assessment of the reaction kinetics with detailed knowledge about the complex phase behaviour of the mixture of the anthracene photodimer and monomer during thermal dissociation.

Covalent Adaptable Networks with Tunable Exchange Rates Based on Reversible Thiol-yne Cross-Linking.

The design of covalent adaptable networks (CANs) relies on the ability to trigger the rearrangement of bonds within a polymer network. Simple activated alkynes are now used as versatile reversible cross-linkers for thiols. The click-like thiol-yne cross-linking reaction readily enables network synthesis from polythiols through a double Michael addition with a reversible and tunable second addition step. The resulting thioacetal cross-linking moieties are robust but dynamic linkages. A series of different activated alkynes have been synthesized and systematically probed for their ability to produce dynamic thioacetal linkages, both in kinetic studies of small molecule models, as well as in stress relaxation and creep measurements on thiol-yne-based CANs. The results are further rationalized by DFT calculations, showing that the bond exchange rates can be significantly influenced by the choice of the activated alkyne cross-linker.