Going with the Flow : Tunable Flow-Induced Polymer Mechanochemistry

Mechanical forces can drive chemical transformations in polymers, directing reactions along otherwise inaccessible pathways, providing exciting possibilities for developing smart, responsive materials. The state-of-the-art test for solution-based polymer mechanochemistry development is ultrasonication. However, this does not accurately model the forces that will be applied during device fabrication using processes such as 3D printing or spray coating. Here, a step is taken toward predictably translating mechanochemistry from molecular design to manufacturing by demonstrating a highly controlled nozzle flow setup in which the shear forces being delivered are precisely tuned. The results show that solvent viscosity, fluid strain rate, and the nature of the breaking bond can be individually studied. Importantly, it is shown that the influence of each is different to that suggested by ultrasonication (altered quantity of chain breakage and critical polymer chain length). Significant development is presented in the understanding of polymer bond breakage during manufacturing flows to help guide design of active components that trigger on demand. Using an anthracene-based mechanophore, the triggering of a fluorescence turn-on is demonstrated through careful selection of the flow parameters. This work opens the avenue for programmed chemical transformations during inline manufacturing processes leading to tunable, heterogeneous final products from a single source material. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Synergistic photoluminescence enhancement in conjugated polymer-di-ureasil organic-inorganic composites.

Poly(fluorene) conjugated polyelectrolyte (CPE)-di-ureasil organic-inorganic composites have been prepared using a versatile sol-gel processing method, which enables selective localisation of the CPE within the di-ureasil matrix. Introduction of the CPE during the sol-gel reaction leads to a homogeneous distribution of the CPE throughout the di-ureasil, whereas a post-synthesis solvent permeation route leads to the formation of a confined layer of the CPE at the di-ureasil surface. The CPE and the di-ureasil both function as photoactive components, contributing directly to, and enhancing the optical properties of their composite material. The bright blue photoluminescence exhibited by CPE-di-ureasils is reminiscent of the parent CPE; however the distinct contribution of the di-ureasil to the steady-state emission profile is also apparent. This is accompanied by a dramatic increase in the photoluminescence quantum yield to >50%, which is a direct consequence of the synergy between the two components. Picosecond time-correlated single photon counting measurements reveal that the di-ureasil effectively isolates the CPE chains, leading to emissive trap sites which have a high radiative probability. Moreover, intimate mixing of the CPE and the di-ureasil, coupled with their strong spectral overlap, results in efficient excitation energy transfer from the di-ureasil to these emissive traps. Given the simple, solution-based fabrication method and the structural tunability of the two components, this approach presents an efficient route to highly desirable CPE-hybrid materials whose optoelectronic properties may be enhanced and tailored for a targeted application

A single-component photorheological fluid with light-responsive viscosity.

Viscoelastic fluids whose rheological properties are tunable with light have the potential to deliver significant impact in fields relying on a change in flow behavior, such as in-use tuning of combined efficient heat-transfer and drag-reduction agents, microfluidic flow and controlled encapsulation and release. However, simple, single-component systems must be developed to allow integration with these applications. Here, we report a single-component viscoelastic fluid, capable of a dramatic light-sensitive rheological response, from a neutral azobenzene photosurfactant, 4-hexyl-4'butyloxymonotetraethylene glycol (C6AzoOC4E4) in water. From cryo-transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS) and rheology measurements, we observe that the photosurfactant forms an entangled network of wormlike micelles in water, with a high viscosity (28 Pa s) and viscoelastic behaviour. UV irradiation of the surfactant solution creates a less dense micellar network, with some vesicle formation. As a result, the solution viscosity is reduced by four orders of magnitude (to 1.2 × 10-3 Pa s). This process is reversible and the high and low viscosity states can be cycled several times, through alternating UV and blue light irradiation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Strategic design of conjugated polymer materials for sensors and solid-state lighting

THESIS 10936Conjugated polymers (CPs) have shown extreme promise in a range of applications such as optical sensors and light-emitting devices due to their exceptional optoelectronic properties, low cost and solution processability. CPs are particularly sought after as sensory materials due to their property of amplified quenching, which can facilitate analyte detection at nanomolar concentrations. This work begins by examining the use of a polyfluorene (blue-emitting)- polythiophene (red-emitting) diblock CP with complementary optoelectronic properties attributed to both blocks, which enables fluorimetric and colorimetric detection of biologically important nucleotides. The magnitude of the optical response is sensitive to both nucleotide geometry and charge. The proposed mechanism behind this process involves electron transfer from the nucleobase to the polythiophene block, mediated by the CP triplet state. Although the vast majority of CP-based sensing schemes involve the detection of electronpoor analytes by electron-rich polymers, there are relatively few examples describing the contrary scenario, electron-rich analyte detection by electron-poor polymers. In Chapter 4, the possibility of increasing the discriminatory action of such electron-poor CP sensor systems through the creation of polyrotaxane species is investigated, whereby macrocycles of differing sizes are exploited to control the effective volume in which the CP and analytes interact. This system may be deposited into the solid-state, whilst retaining its sensing properties to gas phase analytes. The lifetime of any solid-state CP-based device is limited by the photo- and thermal instability of the CP. Incorporation of CPs into an inorganic host allows modulation of the optical properties and aggregation state of the CP, whilst simultaneously improving the environmental stability. However, due to the chemical incompatibility of the two components, inhibiting phase separation across all length scales can be challenging. In Chapters 5-7, the potential of di-ureasil hybrids, comprised of an organic polyether grafted onto a siliceous network via urea linkages, as host materials for CPs is investigated. Firstly, blue-emitting polyfluorene-phenylene CPs were physically immobilised into the di-ureasil to form a Class I hybrid. Examination of the optical properties indicated that both the CPs and the di-ureasil host contribute to the photoluminescence properties giving rise to a dramatic enhancement of the photoluminescence quantum yield (PLQY) to ~60%. This is due to effective prevention of CP aggregation by the di-ureasil host and efficient energy transfer between the two components. Subsequent inclusion of the red-emitting CPs, MEHPPV and P3TMAHT, was carried out in an effort to extend the emission colour from the inherent blue emission of the di-ureasil host across the visible spectrum. The emission colour of these samples was found to be tunable across the blue-white-yellow spectral region due to incomplete F?rster resonance energy transfer from the di-ureasil to the CP. Finally, as the properties of such organic-inorganic hybrid materials depend on the interface between the two phases, a polyfluorene was covalently-grafted directly to the siliceous network of a di-ureasil. Energy transfer between the di-ureasil and the CP was observed leading to an improved PLQY when compared to a thin film of the pure CP. On comparison with the physically immobilized samples previously discussed, the magnitude of energy transfer was found to be reduced for the grafted species. This suggests a reduced interaction between the CP and organic component of the di-ureasil, highlighting the ability to further control the interactions between the CP and di-ureasil through careful selection of the incorporation method. The power of the approach presented in this thesis lies in both its simplicity and versatility. Incorporation within a di-ureasil host has showed improved thermal and photostability for each of the CPs investigated. The electronic coupling between the CPs and the di-ureasil suggests that CPdi-ureasils also offer a wealth of potential applications from composite photovoltaics, to luminescent solar concentrators and optical sensors. While the confinement of the CP within a specific region of an active layer offers the potential to reduce the complexity of multi-layer device architectures and may yield improved device performance

Quantitative monitoring and modelling of retrodialysis drug delivery in a brain phantom

AbstractA vast number of drug molecules are unable to cross the blood-brain barrier, which results in a loss of therapeutic opportunities when these molecules are administered by intravenous infusion. To circumvent the blood-brain barrier, local drug delivery devices have been developed over the past few decades such as reverse microdialysis. Reverse microdialysis (or retrodialysis) offers many advantages, such as a lack of net volume influx to the intracranial cavity and the ability to sample the tumour’s micro-environment. However, the translation of this technique to efficient drug delivery has not been systematically studied. In this work, we present an experimental platform to evaluate the performance of microdialysis devices in reverse mode in a brain tissue phantom. The mass of model drug delivered is measured by computing absorbance fields from optical images. Concentration maps are reconstructed using a modern and open-source implementation of the inverse Abel transform. To illustrate our method, we assess the capability of a commercial probe in delivering methylene blue to a gel phantom. We find that the delivery rate can be described by classical microdialysis theory, except at low dialysate flow rates where it is impacted by gravity, and high flow rates where significant convection to the gel occurs. We also show that the flow rate has an important impact not only on the overall size of the drug plume, but also on its shape. The numerical tools developed for this study have been made freely available to ensure that the method presented can be used to rapidly and inexpensively optimise probe design and protocol parameters before proceeding to more in-depth studies.</jats:p

Theory of flow-induced covalent polymer mechanochemistry in dilute solutions

Acknowledgements: This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), grant no. EP/S009000/1.It is crucial to consider both solvent strain and strain rate when predicting mechanochemistry of polymer solutions in arbitrary flows.EP/S009000/

A Single-Component Photorheological Fluid with Light-Responsive Viscosity

Manuscript and supporting information detailing characterisation of photoresponsive viscoelastic fluids prepared from wormlike micelles composed of azobenzene surfactants. Data includes results from rheology, UV/vis absorption, transmission electron microscopy and small-angle X-ray scattering measurements

A Single-Component Photorheological Fluid with Light-Responsive Viscosity

Manuscript and supporting information detailing characterisation of photoresponsive viscoelastic fluids prepared from wormlike micelles composed of azobenzene surfactants. Data includes results from rheology, UV/vis absorption, transmission electron microscopy and small-angle X-ray scattering measurements.</jats:p