Dihedral angles and photoluminescence quantum yields: an NMR analysis.

The synthesis of two different series of donor-acceptor (D-A) molecules is reported, consisting of a series of four structurally related donors and two different acceptors. The subtle differences in the electron density of these D-A-D and D-A compounds are clearly reflected in the different chemical shifts of certain donor protons in the 1H NMR spectra. These shifts show a cosine squared correlation of the dihedral angle between the donor units and the neighbouring phenyl unit of the acceptor. This correlation is also related to optical properties such as the photoluminescence quantum yield, which shows a similar trend due to the different degree of charge transfer during excitation and relaxation processes. In this way, it is possible to directly correlate a molecular structural parameter with a material property on a purely experimental basis, which should be applicable to many donor-acceptor systems.

A Phosphoramidate Prodrug Platform: One-Pot Amine Functionalization of Kinase Inhibitors with Oligoethylene Glycol for Improved Water-Solubility.

Small molecular kinase inhibitors play a key role in modern cancer therapy. Protein kinases are essential mediators in the growth and progression of cancerous tumors, rendering involved kinases an increasingly important target for therapy. However, kinase inhibitors are almost insoluble in water because of their hydrophobic aromatic nature, often lowering their availability and pharmacological efficacy. Direct drug functionalization with polar groups represents a simple strategy to improve the drug solubility, availability, and performance. Here, we present a strategy to functionalize secondary amines with oligoethylene glycol (OEG) phosphate using a one-step synthesis in three exemplary kinase inhibiting drugs Ceritinib, Crizotinib, and Palbociclib. These OEG-prodrug conjugates demonstrate superior solubility in water compared to the native drugs, with the solubility increasing up to 190-fold. The kinase inhibition potential is only slightly decreased for the conjugates compared to the native drugs. We further show pH dependent hydrolysis of the OEG-prodrugs which releases the native drug. We observe a slow release at pH 3, while the conjugates remain stable over 96 h under physiological conditions (pH 7.4). Using confocal microscopy, we verify improved cell uptake of the drug-OEG conjugates into the cytoplasm of HeLa cells, further supporting our universal solubility approach.

A Stable Chichibabin Diradicaloid with Near-Infrared Emission.

Conjugated molecules with multiple radical centers such as the iconic Chichibabin diradicaloid hold promise as building blocks in materials for quantum sensing and quantum information processing. However, it is a considerable challenge to design simple analogues of the Chichibabin hydrocarbon that are chemically inert, exhibit high diradical character and emit light at a distinct wavelength that may offer an optical readout of the spin state in functional ensembles. Here we describe the serendipitous discovery of the stable TTM-TTM diradicaloid, which exhibits high diradical character, a striking sky-blue color and near-infrared (NIR) emission (in solution). This combination of properties is unique among related diradicaloids and is due to the presence of hydrogen and chlorine atoms in "just the right positions", allowing a perfectly planar, yet predominantly benzenoid bridge to connect the two sterically stabilized radical centers. In-depth studies of the optical and magnetic properties suggest that this structural motif could become a mainstay building block of organic spin materials.

Water-Soluble Trityl Radicals for Fluorescence Imaging.

Stable tris(trichlorophenyl)methyl radicals have gained interest as all-organic bioimaging agents combining fluorescent and paramagnetic properties. However, cellular uptake has so far only been reported for nanoparticles, because molecular hydrophobic trityl radicals are not soluble in aqueous media. Here, we report the synthesis and characterization of new water-soluble tris(trichlorophenyl)methyl radical derivatives exhibiting red doublet emission. Solubility in water is achieved through functionalization with oligoethylene glycol (OEG) chains. The emission behavior of OEG functionalized trityl radicals is studied in polar environments. Donor-functionalization with carbazole evokes a charge-transfer excited state that is efficiently quenched in polar solvents. In contrast, click-reaction mediated attachment of OEG-azide and trityl acetylene furnishes a triazole functionalized radical with locally excited states and emission in water. Confocal fluorescence microscopy proves successful uptake of the material by macrophages in cell culture, showing the potential of our water soluble trityl radical for fluorescence bioimaging.

All-Organic Battery Based on Deep Eutectic Solvent and Redox-Active Polymers.

Sustainable battery concepts are of great importance for the energy storage demands of the future. Organic batteries based on redox-active polymers are one class of promising storage systems to meet these demands, in particular when combined with environmentally friendly and safe electrolytes. Deep Eutectic Solvents (DESs) represent a class of electrolytes that can be produced from sustainable sources and exhibit in most cases no or only a small environmental impact. Because of their non-flammability, DESs are safe, while providing an electrochemical stability window almost comparable to established battery electrolytes and much broader than typical aqueous electrolytes. Here, we report the first all-organic battery cell based on a DES electrolyte, which in this case is composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N-methylacetamide (NMA) alongside the electrode active materials poly(2,2,6,6-tetramethylpiperidin-1-yl-oxyl methacrylate) (PTMA) and crosslinked poly(vinylbenzylviologen) (X-PVBV2+ ). The resulting cell shows two voltage plateaus at 1.07 V and 1.58 V and achieves Coulombic efficiencies of 98 %. Surprisingly, the X-PVBV/X-PVBV+ redox couple turned out to be much more stable in NaTFSI : NMA 1 : 6 than the X-PVBV+ /X-PVBV2+ couple, leading to asymmetric capacity fading during cycling tests.

Deferral of Estimated Glomerular Filtration Rate Testing Before Contrast-Enhanced CT in Low-Risk Emergency Department Patients: Assessment of Safety and Impact on Throughput.

OBJECTIVE: To assess the safety and utility of deferring estimated glomerular filtration rate (eGFR) testing before contrast-enhanced CT (CECT) in low-risk emergency department (ED) patients. METHODS: A new question was added to CECT order screens, allowing ordering ED providers to defer eGFR testing in patients deemed low risk for contrast-induced acute kidney injury (AKI). Low risk was defined as no known chronic kidney disease (CKD) or risk factors for AKI or CKD. Patients on chronic dialysis were deemed low risk. The project included three phases: baseline, pilot (optional order question), and full implementation (required order question). Outcomes were operational throughput metrics of CECT order to protocol (O to P) and order to begin (O to B) times. As a balancing safety measure, the proportion of patients deemed to be "low risk" and subsequently found to have eGFR value less than 30 mL/min/1.73 m2 was reported. RESULTS: A total of 16,446 CECT studies were included from four EDs. In the pilot phase, provider engagement rates with the question were low (5%-14%). After full implementation, median O to P time improved from 23.93 min at baseline to 13.02 (P < .0001) and median O to B time improved from 80.34 min to 76.48 (P = .0002). In 0.3% (2 of 646) studies, CECT was completed in patients categorized as low risk by the ED provider with subsequently resulted eGFR <30 mL/min/1.73 m2. DISCUSSION: Upfront clinical risk assessment for AKI and CKD by ED providers can be used to safely defer eGFR testing and improve operational performance for patients requiring CECT.

Revealing the Origin of Fast Delayed Fluorescence in a Donor Functionalized Bisterpyridine.

A new carbazole-substituted bisterpyridine with pronounced delayed fluorescence is presented. While the molecular donor-acceptor-donor design suggests the origin of this to be thermally activated delayed fluorescence (TADF), results from various photophysical characterizations, OLED characteristics, temperature-dependent NMR spectroscopy, and DFT calculations all point against the involvement of triplet states. The molecule exhibits blue emission at about 440 nm with two or more fast decay channels in the lower nanosecond range in both solution and thin films. The delayed emission is proposed to be caused by rotational vibrational modes. We suggest that these results are generally applicable, especially for more complex molecules, and should be considered as alternative or competitive emissive relaxation pathways in the field of organic light emitting materials.

Varying the Stiffness and Diffusivity of Rod-Shaped Microgels Independently through Their Molecular Building Blocks.

Microgels are water-swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method-all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications. In this report, we systematically vary the architecture and molar mass of polyethylene glycol-acrylate (PEG-Ac) precursors, as well as their concentration and combination, to gain insight in the different parameters that affect the internal structure of rod-shaped microgels. We characterize the mechanical properties and diffusivity, as well as the conversion of acrylate groups during photopolymerization, in both bulk hydrogels and microgels produced from the PEG-Ac precursors. Furthermore, we investigate cell-microgel interaction, and we observe improved cell spreading on microgels with more accessible RGD peptide and with a stiffness in a range of 20 kPa to 50 kPa lead to better cell growth.

Utility of Gadolinium-Based Contrast in Initial Evaluation of Seizures in Children Presenting Emergently.

BACKGROUND AND PURPOSE: The frequency and utility of gadolinium in evaluation of acute pediatric seizure presentation is not well known. The purpose of this study was to assess the utility of gadolinium-based contrast agents in MR imaging performed for the evaluation of acute pediatric seizure presentation. MATERIALS AND METHODS: We identified consecutive pediatric patients with new-onset seizures from October 1, 2016, to September 30, 2021, who presented to the emergency department and/or were admitted to the inpatient unit and had an MR imaging of the brain for the evaluation of seizures. The clinical and imaging data were recorded, including the patient's age and sex, the use of IV gadolinium, and the underlying cause of epilepsy when available. RESULTS: A total of 1884 patients were identified for inclusion. Five hundred twenty-four (28%) patients had potential epileptogenic findings on brain MR imaging, while 1153 (61%) patients had studies with normal findings and 207 (11%) patients had nonspecific signal changes. Epileptogenic findings were subclassified as the following: neurodevelopmental lesions, 142 (27%); intracranial hemorrhage (traumatic or germinal matrix), 89 (17%); ischemic/hypoxic, 62 (12%); hippocampal sclerosis, 44 (8%); neoplastic, 38 (7%); immune/infectious, 20 (4%); phakomatoses, 19 (4%); vascular anomalies, 17 (3%); metabolic, 3 (<1%); and other, 90 (17%). Eight hundred seventy-four (46%) patients received IV gadolinium. Of those, only 48 (5%) cases were retrospectively deemed to have necessitated the use of IV gadolinium: Fifteen of 48 (31%) cases were subclassified as immune/infectious, while 33 (69%) were neoplastic. Of the 1010 patients with an initial noncontrast study, 15 (1.5%) required repeat MR imaging with IV contrast to further evaluate the findings. CONCLUSIONS: Gadolinium contrast is of limited additive benefit in the imaging of patients with an acute onset of pediatric seizures in most instances.

Microgels as Platforms for Antibody-Mediated Cytokine Scavenging.

Therapeutic antibodies are the key treatment option for various cytokine-mediated diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, systemic injection of these antibodies can cause side effects and suppress the immune system. Moreover, clearance of therapeutic antibodies from the blood is limiting their efficacy. Here, water-swollen microgels are produced with a size of 25 µm using droplet-based microfluidics. The microgels are functionalized with TNFα antibodies to locally scavenge the pro-inflammatory cytokine TNFα. Homogeneous distribution of TNFα-antibodies is shown throughout the microgel network and demonstrates specific antibody-antigen binding using confocal microscopy and FLIM-FRET measurements. Due to the large internal accessibility of the microgel network, its capacity to bind TNFα is extremely high. At a TNFα concentration of 2.5 µg mL-1 , the microgels are able to scavenge 88% of the cytokine. Cell culture experiments reveal the therapeutic potential of these microgels by protecting HT29 colorectal adenocarcinoma cells from TNFα toxicity and resulting in a significant reduction of COX II and IL8 production of the cells. When the microgels are incubated with stimulated human macrophages, to mimic the in vivo situation of inflammatory bowel disease, the microgels scavenge almost all TNFα that is produced by the cells.

A Photopatternable Conjugated Polymer with Thermal-Annealing-Promoted Interchain Stacking for Highly Stable Anti-Counterfeiting Materials.

Photoresponsive polymers can be conveniently used to fabricate anti-counterfeiting materials through photopatterning. However, an unsolved problem is that ambient light and heat can damage anti-counterfeiting patterns on photoresponsive polymers. Herein, photo- and thermostable anti-counterfeiting materials are developed by photopatterning and thermal annealing of a photoresponsive conjugated polymer (MC-Azo). MC-Azo contains alternating azobenzene and fluorene units in the polymer backbone. To prepare an anti-counterfeiting material, an MC-Azo film is irradiated with polarized blue light through a photomask, and then thermally annealed under the pressure of a photonic stamp. This strategy generates a highly secure anti-counterfeiting material with dual patterns, which is stable to sunlight and heat over 200 °C. A key for the stability is that thermal annealing promotes interchain stacking, which converts photoresponsive MC-Azo to a photostable material. Another key for the stability is that the conjugated structure endows MC-Azo with desirable thermal properties. This study shows that the design of photopatternable conjugated polymers with thermal-annealing-promoted interchain stacking provides a new strategy for the development of highly stable and secure anti-counterfeiting materials.

Switchable Polyacrylonitrile-Copolymer for Melt-Processing and Thermal Carbonization-3D Printing of Carbon Supercapacitor Electrodes with High Capacitance.

Polyacrylonitrile (PAN) represents the most widely used precursor for carbon fibers and carbon materials. Carbon materials stand out with their high mechanical performance, but they also show excellent electrical conductivity and high surface area. These properties render carbon materials suitable as electrode material for fuel cells, batteries, and supercapacitors. However, PAN has to be processed from solution before being thermally converted to carbon, limiting its final format to fibers, films, and non-wovens. Here, a PAN-copolymer with an intrinsic plasticizer is presented to reduce the melting temperature and avoid undesired entering of the thermal carbonization regime. This plasticizer enables melt extrusion-based additive manufacturing (EAM). The plasticizer in the PAN-copolymer can be switched to increase the melting temperature after processing, allowing the 3D-melt-printed workpiece to be thermally carbonized after EAM. Melt-processing of the PAN copolymer extends the freedom-in-design of carbon materials to mold-free rapid prototyping, in the absence of solvents, which enables more economic and sustainable manufacturing processes. As an example for the capability of this material system, open meshed carbon electrodes are printed for supercapacitors that are metal- and binder-free with an optimized thickness of 1.5 mm and a capacitance of up to 387 mF cm-2 .

Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients.

OBJECTIVE: There is a lack of data supporting cancer surveillance in pediatric Fanconi Anemia patients. We sought to describe the rates of upper aerodigestive lesions and malignancy in this population to augment current management guidelines. METHODS: A retrospective cohort study of patients with Fanconi Anemia from a quaternary referral center between 2007-2021 was completed for head and neck cancer risk. RESULTS: One hundred and five FA patients were reviewed. Average age at presentation was 11.3 years old and 90.5% of patients underwent hematopoietic stem cell transplant (HSCT). A total of 8.6% of patients had leukoplakia or erythroplakia and 3.8% developed malignancy. The standardized incidence ratio of head and neck malignancy was 483.8. Patients presented with leukoplakia and malignancy at an average age of 14.6 and 25.1 years old, respectively. Malignancies were aggressive and marked by recurrence. There were no premalignant or malignant lesions found on flexible laryngoscopy. This series represents the largest longitudinal series of pediatric FA head and neck lesions. CONCLUSIONS: Fanconi Anemia patients should begin screening for head and neck cancer at age 10 or after HSCT. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 133:1745-1748, 2023.

Combining Deep Eutectic Solvents with TEMPO-based Polymer Electrodes: Influence of Molar Ratio on Electrode Performance.

For sustainable energy storage, all-organic batteries based on redox-active polymers promise to become an alternative to lithium ion batteries. Yet, polymers contribute to the goal of an all-organic cell as electrodes or as solid electrolytes. Here, we replace the electrolyte with a deep eutectic solvent (DES) composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N-methylacetamide (NMA), while using poly(2,2,6,6-tetramethylpiperidin-1-yl-oxyl methacrylate) (PTMA) as cathode. The successful combination of a DES with a polymer electrode is reported here for the first time. The electrochemical stability of PTMA electrodes in the DES at the eutectic molar ratio of 1 : 6 is comparable to conventional battery electrolytes. More viscous electrolytes with higher salt concentration can hinder cycling at high rates. Lower salt concentration leads to decreasing capacities and faster decomposition. The eutectic mixture of 1 : 6 is best suited uniting high stability and moderate viscosity.

Enhanced Stable Cavitation and Nonlinear Acoustic Properties of Poly(butyl cyanoacrylate) Polymeric Microbubbles after Bioconjugation.

Microbubbles (MB) are used as ultrasound (US) contrast agents in clinical settings because of their ability to oscillate upon exposure to acoustic pulses and generate nonlinear responses with a stable cavitation profile. Polymeric MB have recently attracted increasing attention as molecular imaging probes and drug delivery agents based on their tailorable acoustic responses, high drug loading capacity, and surface functionalization capabilities. While many of these applications require MB to be functionalized with biological ligands, the impact of bioconjugation on polymeric MB cavitation and acoustic properties remains poorly understood. Hence, we here evaluated the effects of MB shell hydrolysis and subsequent streptavidin conjugation on the acoustic behavior of poly(butyl cyanoacrylate) (PBCA) MB. We show that upon biofunctionalization, MB display higher acoustic stability, stronger stable cavitation, and enhanced second harmonic generation. Furthermore, functionalized MB preserve the binding capabilities of streptavidin conjugated on their surface. These findings provide insights into the effects of bioconjugation chemistry on polymeric MB acoustic properties, and they contribute to improving the performance of polymer-based US imaging and theranostic agents.

Carbodiimide-Driven Dimerization and Self-Assembly of Artificial, Ribose-Based Amphiphiles.

The aqueous self-assembly of amphiphiles into aggregates such as micelles and vesicles has been widely investigated over the past decades with applications ranging from materials science to drug delivery. The combination of characteristic properties of nucleic acids and amphiphiles is of substantial interest to mimic biological self-organization and compartmentalization. Herein, we present ribose- and ribonucleotide-based amphiphiles and investigate their self-assembly as well as their fundamental reactivity. We found that various types of aggregates are formed, ranging in size from nanometers to micrometers and all amphiphiles exhibit aggregation-induced emission (AIE) in solution as well as in the solid state. We also observed that the addition of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) leads to rapid and selective dimerization of the amphiphiles into pyrophosphates, which decreases the critical aggregation concentration (CAC) by a factor of 25 when compared to the monomers. Since the propensity for amphiphile dimerization is correlated with their tendency to self-assemble, our results may be relevant for the formation of rudimentary compartments under prebiotic conditions.

On-Chip Direct Laser Writing of PAN-Based Carbon Supercapacitor Electrodes.

The carbonization of polyacrylonitrile (PAN) by direct laser writing to produce microsupercapacitors directly on-chip is reported. The process is demonstrated by producing interdigitated carbon finger electrodes directly on a printed circuit board (PCB), which is then employed to characterize the supercapacitor electrodes. By varying the laser power, the process can be tuned from carbonization to material ablation. This allows to not only convert pristine PAN films into carbon electrodes, but also to pattern and cut away non-carbonized material to produce completely freestanding carbon electrodes. While the carbon electrodes adhere well to the printed circuit board, non-carbonized PAN is peeled off the substrate. Specific capacities as high as 260 µF cm⁻2 are achieved in a supercapacitor with 16 fingers.

Translating Therapeutic Microgels into Clinical Applications.

Microgels are crosslinked, water-swollen networks with a 10 nm to 100 µm diameter and can be modified chemically or biologically to render them biocompatible for advanced clinical applications. Depending on their intended use, microgels require different mechanical and structural properties, which can be engineered on demand by altering the biochemical composition, crosslink density of the polymer network, and the fabrication method. Here, the fundamental aspects of microgel research and development, as well as their specific applications for theranostics and therapy in the clinic, are discussed. A detailed overview of microgel fabrication techniques with regards to their intended clinical application is presented, while focusing on how microgels can be employed as local drug delivery materials, scavengers, and contrast agents. Moreover, microgels can act as scaffolds for tissue engineering and regeneration application. Finally, an overview of microgels is given, which already made it into pre-clinical and clinical trials, while future challenges and chances are discussed. This review presents an instructive guideline for chemists, material scientists, and researchers in the biomedical field to introduce them to the fundamental physicochemical properties of microgels and guide them from fabrication methods via characterization techniques and functionalization of microgels toward specific applications in the clinic.

Biodegradable Polyimidazole Particles as Contrast Agents Produced by Direct Arylation Polymerization.

Conjugated polymer particles provide an important platform for the development of theranostic nanoagents. However, the number of biocompatible and foremost biodegradable π-conjugated polymers is limited. Imidazole is a π-conjugated motif that is abundant in biological systems. Oxidative degradation of imidazole is present in nature via enzymatic or free radical processes. In this work, we introduce polymer particles consisting purely of polyimidazole. We employ direct arylation polymerization and adapt it to a dispersion polymerization protocol to yield uniform and narrowly dispersed nanoparticles. We employ this mechanism to produce linear and cross-linked polymer particles to tune the optical properties from fluorescent to photoacoustically active. We show that the particles can be degraded by H2O2 as well as by reactive oxygen species produced by cells and we detect the degradation products. Altogether, our results suggest that polyimidazole particles represent ideal candidates for theranostic applications.

Understanding hierarchical spheres-in-grating assembly for bio-inspired colouration.

The vivid iridescent response from particular butterflies is as an excellent example of how micro-engineered hierarchical architectures that combine physical structures and pigmentary inclusions create unique colouration. To date, however, detailed knowledge is missing to replicate such sophisticated structures in a robust, reliable manner. Here, we deliver spheres-in-grating assemblies with colouration effects as found in nature, exploiting embossed polymer gratings and self-assembled light-absorbing micro-spheres.