Macromolecular Function Emerging from Intramolecular Peptide Stapling of Synthetic Polymers.

Protein function results from the precise folding of polypeptides into bespoke architectures. Taking inspiration from nature, the field of single-chain nanoparticles (SCNPs), intramolecularly crosslinked synthetic polymers, emerged. In contrast to nature, the function of SCNPs is generally defined by the parent polymer or the applied crosslinker, rather than by the crosslinking process itself.

Visible light photoflow synthesis of a Cu(ii) single-chain polymer nanoparticle catalyst.

We herein pioneer the visible light ( = 410 nm) mediated flow synthesis of catalytically active single-chain nanoparticles (SCNPs). Our design approach is based on a copolymer of poly(ethylene glycol) methyl ether methacrylate and a photocleavable 2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate monomer which can liberate amine groups upon visible light irradiation, allowing for single-chain collapse the complexation of Cu(ii) ions. We initially demonstrate the successful applicability of our design approach for the batch photochemical synthesis of Cu(ii) SCNPs and transfer the concept to photoflow conditions, enabling, for the first time, the continuous production of functional SCNPs.

Main chain selective polymer degradation: controlled by the wavelength and assembly.

The advent of reversible deactivation radical polymerization (RDRP) revolutionized polymer chemistry and paved the way for accessing synthetic polymers with controlled sequences based on vinylic monomers. An inherent limitation of vinylic polymers stems from their all-carbon backbone, which limits both function and degradability. Herein, we report a synthetic strategy utilizing radical ring-opening polymerization (rROP) of complementary photoreactive cyclic monomers in combination with RDRP to embed photoresponsive functionality into desired blocks of polyvinyl polymers.

How molecular architecture defines quantum yields.

Understanding the intricate relationship between molecular architecture and function underpins most challenges at the forefront of chemical innovation. Bond-forming reactions are particularly influenced by the topology of a chemical structure, both on small molecule scale and in larger macromolecular frameworks. Herein, we elucidate the impact that molecular architecture has on the photo-induced cyclisations of a series of monodisperse macromolecules with defined spacers between photodimerisable moieties, and examine the relationship between propensity for intramolecular cyclisation and intermolecular network formation.

Plenty of Space in the Backbone: Radical Ring-Opening Polymerization.

Radical polymerization is the most widely applied technique in both industry and fundamental science. However, its major drawback is that it typically yields polymers with non-functional, non-degradable all-carbon backbones-a limitation that radical ring-opening polymerization (rROP) allows to overcome. The last decade has seen a surge in rROP, primarily focused on creating degradable polymers.

Förster resonance energy transfer within single chain nanoparticles.

Single chain nanoparticles (SCNPs) are a highly versatile polymer architecture consisting of single polymer chains that are intramolecularly crosslinked. Currently, SCNPs are discussed as powerful macromolecular architectures for catalysis, delivery and sensors. Herein, we introduce a methodology based on Förster Resonance Energy Transfer (FRET) to evidence the folding of single polymer chains into SCNPs fluorescence readout.

Photochemical Action Plots Reveal Red-shifted Wavelength-dependent Photoproduct Distributions.

Photochemical action plots are a powerful tool for mapping photochemical reaction outcomes wavelength-by-wavelength. Typically, they map either the depletion of a reactant or the formation of a specific product as a function of wavelength. Herein, we exploit action plots to simultaneously map the formation of several photochemical products from a single chromophore.

pH-Controlled Reversible Folding of Copolymers via Formation of β-sheet Secondary Structures.

Protein functions are enabled by their perfectly arranged 3D structure, which is the result of a hierarchical intramolecular folding process. Sequence-defined polypeptide chains form locally ordered secondary structures (i.e.

Simultaneously recorded photochemical action plots reveal orthogonal reactivity.

We map the photochemical reactivity of two chromophores-a pyrene-chalcone and a methylene blue protected amine-from a one-pot reaction mixture based on their dynamic absorptivity changes upon light exposure, constructing a dual action plot. We employ the action plot data to determine a pathlength-independent λ-orthogonality window, allowing the orthogonal folding of distinct polymer chains into single chain nano-particles (SCNPs) from the same reaction mixture.

Visible-Light-Induced Control over Reversible Single-Chain Nanoparticle Folding.

We introduce a class of single-chain nanoparticles (SCNPs) that respond to visible light (λ =415 nm) with complete unfolding from their compact structure into linear chain analogues. The initial folding is achieved by a simple esterification reaction of the polymer backbone constituted of acrylic acid and polyethylene glycol carrying monomer units, introducing bimane moieties, which allow for the photochemical unfolding, reversing the ester-bond formation. The compaction and the light driven unfolding proceed cleanly and are readily followed by size exclusion chromatography (SEC) and diffusion ordered NMR spectroscopy (DOSY), monitoring the change in the hydrodynamic radius (R ).

Peptide Self-Assembly Controlled Photoligation of Polymers.

Highly efficient chemical ligations that operate in water under mild conditions are the foundation of bioorthogonal chemistry. However, the toolbox of suitable reactions is limited. Conventional approaches to expand this toolbox aim at altering the inherent reactivity of functional groups to design new reactions that meet the required benchmarks.

Simulation of a Compton-based detector for low-dose high-resolution time-of-flight positron emission tomography.

Two major challenges in time-of-flight positron emission tomography (TOF-PET) are low spatial resolution and high radioactive dose to the patient, both of which result from limitations in detection technology rather than fundamental physics. A new type of TOF-PET detector employing low-atomic number (low-Z) scintillation media and large-area, high-resolution photodetectors to record Compton scattering locations in the detector has been proposed as a promising alternative, but the minimum technical requirements for such a system have not yet been established. Here we present a simulation study evaluating the potential of a proposed low-Z detection medium, linear alkylbenzene (LAB) doped with a switchable molecular recorder, for next-generation TOF-PET detection.

Ferrocene-driven single-chain polymer compaction.

We introduce single-chain nanoparticles (SCNPs) exclusively folded by covalently bonded ferrocene units. Specifially, we demonstrate the ability of 2-ferrocenyl-1,10-phenanthroline to fuse single-chain collapse with the concomitant introduction of a donor functionality allowing the installation of a Pd-catalytic site, affording the first heterobimetallic ferrocene-functionalized SCNP.

Embedding Peptides into Synthetic Polymers: Radical Ring-Opening Copolymerization of Cyclic Peptides.

Biopolymers such as proteins and nucleic acids are the key building blocks of life. Synthetic polymers have nevertheless revolutionized our everyday life through their robust synthetic accessibility. Combining the unmatched functionality of biopolymers with the robustness of tailorable synthetic polymers holds the promise to create materials that can be designed ad hoc for a wide array of 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.

Programming Photodegradability into Vinylic Polymers via Radical Ring-Opening Polymerization.

Incorporation of photolabile moieties into the polymer backbone holds promise to remotely-control polymer degradation. However, suitable synthetic avenues are limited, especially for radical polymerizations. Here we report a strategy to program photodegradability into vinylic polymers by exploiting the wavelength selectivity of photocycloadditions for radical ring-opening polymerization (rROP).

Red light induced folding of single polymer chains.

We pioneer the photochemical generation of single chain nanoparticles (SCNPs) at the to-date mildest reported wavelength of 625 nm by exploiting the photochemical uncaging of methylene blue protected amines. The protected amines are tethered to polymers prepared reversible addition-fragmentation chain transfer (RAFT) polymerisation, and subsequently undergo intrachain crosslinking by amide formation.

High-risk ankle fractures in high-risk older patients: to fix or nail?

Introduction: Optimal treatment of high-risk ankle fractures in older, comorbid patients is unknown. Results of open reduction internal fixation (ORIF) versus tibiotalocalcaneal (TTC) fusion nailing for the treatment of high-risk geriatric ankle fractures were investigated.

Materials And Methods: Results of ORIF versus TTC fusion nailing were evaluated via retrospective case-control cohort study of 60 patients over age 50 with an open ankle fracture or one with at least 50% talar subluxation and at least 1 high-risk comorbidity: diabetes mellitus (DM), peripheral vascular disease, immunosuppression, active smoking, or a BMI > 35.

Photostationary State in Dynamic Covalent Networks.

We explore a cross-linked polymer network based on a visible light photodynamic [2 + 2] cycloaddition driven by styrylpyrene chemistry. Based on a polymer backbone with pendent styrylpyrene units, the network can be formed by using λ = 450 nm irradiation. Upon irradiation with λ = 340 nm, a photostationary state is generated within the network with ∼17% of the styrylpyrene units open compared to close to 2% in the visible light cured state.

Green light enabled Staudinger-Bertozzi ligation.

We introduce a visible light-induced Staudinger-Bertozzi ligation photo-uncaging of a triphenylphosphine moiety with a photolabile coumarin derivative. Our action plot study examines the conversion as the function of wavelength, revealing that the uncaging process and Staudinger reaction can be triggered by green light ( < 550 nm). We further demonstrate the applicability of our approach in materials science endgroup modification of water soluble poly(ethylene glycol) and green light-induced patterning of a solid substrate.

Orange-Light-Induced Photochemistry Gated by pH and Confined Environments.

We introduce a new photochemically active compound, i.e., pyridinepyrene (PyPy), entailing a pH-active moiety that effects a significant halochromic shift into orange-light (λ = 590 nm) activatable photoreactivity while concomitantly exerting control over its reaction pathways.

Action Plots in Action: In-Depth Insights into Photochemical Reactivity.

Predicting wavelength-dependent photochemical reactivity is challenging. Herein, we revive the well-established tool of measuring action spectra and adapt the technique to map wavelength-resolved covalent bond formation and cleavage in what we term "photochemical action plots". Underpinned by tunable lasers, which allow excitation of molecules with near-perfect wavelength precision, the photoinduced reactivity of several reaction classes have been mapped in detail.

Low-Dose High-Resolution TOF-PET Using Ionization-activated Multi-State Low-Z Detector Media.

We propose PET scanners using low atomic number media that undergo a persistent local change of state along the paths of the Compton recoil electrons. Measurement of the individual scattering locations and angles, deposited energies, and recoil electron directions allows using the kinematical constraints of the 2-body Compton scattering process to perform a statistical time-ordering of the scatterings, with a high probability of precisely identifying where the gamma first interacted in the detector. In these cases the Line-of-Response is measured with high resolution, determined by the underlying physics processes and not the detector segmentation.

Wavelength-Selective Softening of Hydrogel Networks.

Photoresponsive hydrogels hold key potential in advanced biomedical applications including tissue engineering, regenerative medicine, and drug delivery, as well as intricately engineered functions such as biosensing, soft robotics, and bioelectronics. Herein, the wavelength-dependent degradation of bio-orthogonal poly(ethylene glycol) hydrogels is reported, using three selective activation levels. Specifically, three chromophores are exploited, that is, ortho-nitrobenzene, dimethyl aminobenzene, and bimane, each absorbing light at different wavelengths.