Polymers without Petrochemicals: Sustainable Routes to Conventional Monomers.

Access to a wide range of plastic materials has been rationalized by the increased demand from growing populations and the development of high-throughput production systems. Plastic materials at low costs with reliable properties have been utilized in many everyday products. Multibillion-dollar companies are established around these plastic materials, and each polymer takes years to optimize, secure intellectual property, comply with the regulatory bodies such as the Registration, Evaluation, Authorisation and Restriction of Chemicals and the Environmental Protection Agency and develop consumer confidence. Therefore, developing a fully sustainable new plastic material with even a slightly different chemical structure is a costly and long process. Hence, the production of the common plastic materials with exactly the same chemical structures that does not require any new registration processes better reflects the reality of how to address the critical future of sustainable plastics. In this review, we have highlighted the very recent examples on the synthesis of common monomers using chemicals from sustainable feedstocks that can be used as a like-for-like substitute to prepare conventional petrochemical-free thermoplastics.

Thermoreversible [2 + 2] Photodimers of Monothiomaleimides and Intrinsically Recyclable Covalent Networks Thereof.

The development of intrinsically recyclable cross-linked materials remains challenged by the inherently unfavorable chemical equilibrium that dictates the efficiency of the reversible covalent bonding/debonding chemistry. Rather than having to (externally) manipulate the bonding equilibrium, we here introduce a new reversible chemistry platform based on monosubstituted thiomaleimides that can undergo complete and independent light-activated covalent bonding and on-demand thermal debonding above 120 °C. Specifically, repeated bonding/debonding of a small-molecule thiomaleimide [2 + 2] photodimer is demonstrated over five heat/light cycles with full conversion in both directions, thereby regenerating its initial monothiomaleimide constituents. This motivated the synthesis of multifunctional thiomaleimide reagents as precursors for the design of covalently cross-linked networks that display intrinsic switching between a monomeric and polymeric state. The resulting materials are shown to covalently dissociate and depolymerize upon heating both in solution and in bulk, thus transforming the densely photo-cross-linked material back into a viscous liquid. Temperature-regulated photorheology evidenced the intrinsic recyclability of the thiomaleimide-based thermosets during multiple cycles of UV cross-linking and thermal de-cross-linking. The thermally reversible photodimerization of thiomaleimides presents a new addition to the designer playground of dynamic polymer networks, providing interesting opportunities for the reprocessing and closed-loop recycling of covalently cross-linked materials.

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.

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.

Light-Stabilized Dynamic Materials.

The light-responsive adaptation of polymer materials typically requires different wavelengths or additional heat to induce reversible covalent bond formation and dissociation. Here, we bypass the use of invasive triggers by introducing light-stabilized dynamic materials that can undergo a repeatable change in topology from a covalently cross-linked material into a liquid polymer formulation by switching one visible light source on-and-off without the need for any additional triggers. Specifically, we exploit the photo-Diels-Alder reaction of triazolinediones with naphthalenes as a dynamic covalent cross-linking platform that enables green light-induced network formation, while the cross-linked material collapses through spontaneous cycloreversion upon standing in the dark at ambient temperature. Importantly, the covalent cross-links remain stabilized for as long as visible light is present, thereby retaining the material's structural integrity. This enables their potential use in an array of light-directed applications whereby network properties such as stiffness can be tuned by the mildest trigger of all: darkness.

Triazolinediones as Highly Enabling Synthetic Tools.

Triazolinediones (TADs) are unique reagents in organic synthesis that have also found wide applications in different research disciplines, in spite of their somewhat "exotic" reputation. In this review, we offer two case studies that demonstrate the possibilities of these versatile and reliable synthetic tools, namely, in the field of polymer science as well as in more recently emerging applications in the field of click chemistry. As the general use of triazolinediones has always been hampered by the limited commercial and synthetic availability of such reagents, we also offer a review of the available TAD reagents, together with a detailed discussion of their synthesis and reactivity. This review thus aims to serve as a practical guide for researchers that are interested in exploiting and further developing the exceptional click-like reactivity of triazolinediones in various applications.

Two Functions from a Single Photoresist: Tuning Microstructure Degradability from Light-Stabilized Dynamic Materials.

A photoresist-based on a light-stabilized dynamic material driven by an out-of-equilibrium photo-Diels-Alder reaction of triazolinediones with naphthalenes-whose ability to intrinsically degrade postprinting can be tuned by a simple adjustment of laser intensity during 3D laser lithography is introduced. The resist's ability to form stable networks under green light irradiation that degrade in the dark is transformed into a tunable degradable 3D printing material platform. In-depth characterization of the printed microstructures via atomic force microscopy before and during degradation reveals the high dependency of the final structures' properties on the writing parameters. Upon identifying the ideal writing parameters and their effect on the network structure, it is possible to selectively toggle between stable and fully degradable structures. This simplifies the direct laser writing manufacturing process of multifunctional materials significantly, which typically requires the use of separate resists and consecutive writing efforts to achieve degradable and nondegradable material sections.

Photocrosslinking of Polyacrylamides Using [2 + 2] Photodimerisation of Monothiomaleimides.

The [2 + 2] photocycloaddition of monothiomaleimides (MTMs) has been exploited for the photocrosslinking of polyacrylamides. Polymer scaffolds composed of dimethylacrylamide and varying amounts of d,l-homocysteine thiolactone acrylamide (5, 10, and 20 mol %) were synthesized via free-radical polymerization, whereby the latent thiol functionality was exploited to incorporate MTM motifs. Subsequent exposure to UV light (λ = 365 nm, 15 mW cm-2) triggered intermolecular crosslinking via the photodimerization of MTM side chains, thus resulting in the formation of polyacrylamide gels. The polymer scaffolds were characterized using Fourier transform infrared spectroscopy, UV-visible spectroscopy, 1H NMR spectroscopy, and size exclusion chromatography, confirming the occurrence of the [2 + 2] photocycloaddition between the MTM moieties. The mechanical and physical properties of the resulting gels containing various MTM mol % were evaluated by rheology, compression testing, and swelling experiments. In addition, scanning electron microscopy was used to characterize the xerogel morphology of 5 and 10 mol % MTM hydro- and organo-gels. The macro-porous morphology obtained for the hydrogels was attributed to phase separation due to the difference in solubility of the PDMA modified with thiolactone side chains, provided that a more homogeneous morphology was obtained when the photo-gels were prepared in DMF as the solvent.

Aggregation-Induced Emission Poly(meth)acrylates for Photopatterning via Wavelength-Dependent Visible-Light-Regulated Controlled Radical Polymerization in Batch and Flow Conditions.

A robust wavelength-dependent visible-light-regulated reversible-deactivation radical polymerization protocol is first reported for the batch preparation of >20 aggregation-induced emission (AIE)-active polyacrylates and polymethacrylates. The resulting polymers possess narrow molar mass distributions (D ≈ 1.09-1.25) and high end-group fidelity at high monomer conversions (mostly >95%). This demonstrated control provides facile access to the in situ generation of complex sequence-defined tetrablock copolymers in one reactor, even while chain extending from less reactive monomers. Polymerizations can be successfully carried out under various irradiation conditions, including using UV, blue, green, and red LED light with more disperse polymers obtained at the longer, less energetic, wavelengths. We observe a red shift and wavelength dependence for the most efficient polymerization using LED illumination in a polymerization reaction. We find that the absorption of the copper(II) complex is not a reliable guide to reaction conditions. Moreover, the reported protocol is readily translated to a flow setup. The prepared AIE-active polymers are demonstrated to exhibit good photopatterning, making them promising materials for applications in advanced optoelectronic devices.

Force-reversible chemical reaction at ambient temperature for designing toughened dynamic covalent polymer networks.

Force-reversible C-N bonds, resulting from the click chemistry reaction between triazolinedione (TAD) and indole derivatives, offer exciting opportunities for molecular-level engineering to design materials that respond to mechanical loads. Here, we displayed that TAD-indole adducts, acting as crosslink points in dry-state covalently crosslinked polymers, enable materials to display reversible stress-responsiveness in real time already at ambient temperature. Whereas the exergonic TAD-indole reaction results in the formation of bench-stable adducts, they were shown to dissociate at ambient temperature when embedded in a polymer network and subjected to a stretching force to recover the original products. Moreover, the nascent TAD moiety can spontaneously and immediately be recombined after dissociation with an indole reaction partners at ambient temperature, thus allowing for the adjustment of the polymer segment conformation and the maintenance of the network integrity by force-reversible behaviors. Overall, our strategy represents a general method to create toughened covalently crosslinked polymer materials with simultaneous enhancement of mechanical strength and ductility, which is quite challenging to achieve by conventional chemical methods.

Light-fueled dynamic covalent crosslinking of single polymer chains in non-equilibrium states.

While polymer synthesis proceeds predominantly towards the thermodynamic minimum, living systems operate on the reverse principle - consuming fuel to maintain a non-equilibrium state. Herein, we report the controlled formation of 3D macromolecular architectures based on light-fueled covalent non-equilibrium chemistry. In the presence of green light (525 nm) and a bivalent triazolinedione (TAD) crosslinker, naphthalene-containing polymers can be folded into single chain nanoparticles (SCNPs). At ambient temperature, the cycloaddition product of TAD with naphthalene reverts and the SCNP unfolds into its linear parent polymer. The reported SCNP is the first example of a reversible light triggered folding of single polymer chains and can readily be repeated for several cycles. The folded state of the SCNP can either be preserved through a constant supply of light fuel, kinetic trapping or through a chemical modification that makes the folded state thermodynamically favored. Whereas small molecule bivalent TAD/naphthalene cycloaddition products largely degraded after 3 days in solution, even in the presence of fuel, the SCNP entities were found to remain intact, thereby indicating the light-fueled stabilization of the SCNP to be an inherent feature of the confined macromolecular environment.

Shining Light on Poly(ethylene glycol): From Polymer Modification to 3D Laser Printing of Water Erasable Microstructures.

The implementation of stimuli-responsive bonds into 3D network assemblies is a key concept to design adaptive materials that can reshape and degrade. Here, a straightforward but unique photoresist is introduced for the tailored fabrication of poly(ethylene glycol) (PEG) materials that can be readily erased by water, even without the need for acidic or basic additives. Specifically, a new class of photoresist is developed that operates through the backbone crosslinking of PEG when irradiated in the presence of a bivalent triazolinedione. Hence, macroscopic gels are obtained upon visible light-emitting diode irradiation (λ > 515 nm) that are stable in organic media but rapidly degrade upon the addition of water. Photoinduced curing is also applicable to multiphoton laser lithography (λ > 700 nm), hence providing access to 3D printed microstructures that vanish when immersed in water at 37 °C. Materials with varying crosslinking densities are accessed by adapting the applied laser writing power, thereby allowing for tunable hydrolytic erasing timescales. A new platform technology is thus presented that enables the crosslinking and 3D laser printing of PEG-based materials, which can be cleaved and erased in water, and additionally holds potential for the facile modification and backbone degradation of polyether-containing materials in general.

From Sequence-Defined Macromolecules to Macromolecular Pin Codes.

Dynamic sequence-defined oligomers carrying a chemically written pin code are obtained through a strategy combining multicomponent reactions with the thermoreversible addition of 1,2,4-triazoline-3,5-diones (TADs) to indole substrates. The precision oligomers are specifically designed to be encrypted upon heating as a result of the random reshuffling of the TAD-indole covalent bonds within the backbone, thereby resulting in the scrambling of the encoded information. The encrypted pin code can eventually be decrypted following a second heating step that enables the macromolecular pin code to be deciphered using 1D electrospray ionization-mass spectrometry (ESI-MS). The herein introduced concept of encryption/decryption represents a key advancement compared with current strategies that typically use uncontrolled degradation to erase and tandem mass spectrometry (MS/MS) to analyze, decipher, and read-out chemically encrypted information. Additionally, the synthesized macromolecules are coated onto a high-value polymer material, which demonstrates their potential application as coded product tags for anti-counterfeiting purposes.

Controlling thermal reactivity with different colors of light.

The ability to switch between thermally and photochemically activated reaction channels with an external stimulus constitutes a key frontier within the realm of chemical reaction control. Here, we demonstrate that the reactivity of triazolinediones, powerful coupling agents in biomedical and polymer research, can be effectively modulated by an external photonic field. Specifically, we show that their visible light-induced photopolymerization leads to a quantitative photodeactivation, thereby providing a well-defined off-switch of their thermal reactivity. Based on this photodeactivation, we pioneer a reaction manifold using light as a gate to switch between a UV-induced Diels-Alder reaction with photocaged dienes and a thermal addition reaction with alkenes. Critically, the modulation of the reactivity by light is reversible and the individually addressable reaction pathways can be repeatedly accessed. Our approach thus enables a step change in photochemically controlled reactivity, not only in small molecule ligations, yet importantly in controlled surface and photoresist design.

Design of a thermally controlled sequence of triazolinedione-based click and transclick reactions.

The reaction of triazolinediones (TADs) and indoles is of particular interest for polymer chemistry applications, as it is a very fast and irreversible additive-free process at room temperature, but can be turned into a dynamic covalent bond forming process at elevated temperatures, giving a reliable bond exchange or 'transclick' reaction. In this paper, we report an in-depth study aimed at controlling the TAD-indole reversible click reactions through rational design of modified indole reaction partners. This has resulted in the identification of a novel class of easily accessible indole derivatives that give dynamic TAD-adduct formation at significantly lower temperatures. We further demonstrate that these new substrates can be used to design a directed cascade of click reactions of a functionalized TAD moiety from an initial indole reaction partner to a second indole, and finally to an irreversible reaction partner. This controlled sequence of click and transclick reactions of a single TAD reagent between three different substrates has been demonstrated both on small molecule and macromolecular level, and the factors that control the reversibility profiles have been rationalized and guided by mechanistic considerations supported by theoretical calculations.