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Abstract The spread of Plasmodium falciparum parasites resistant to most first-line antimalarials creates an imperative to enrich the drug discovery pipeline, preferably with curative compounds that can also act prophylactically. We report a phenotypic quantitative high-throughput screen (qHTS), based on concentration–response curves, which was designed to identify compounds active against Plasmodium liver and asexual blood stage parasites. Our qHTS screened over 450,000 compounds, tested across a range of 5 to 11 concentrations, for activity against Plasmodium falciparum asexual blood stages. Active compounds were then filtered for unique structures and drug-like properties and subsequently screened in a P. berghei liver stage assay to identify novel dual-active antiplasmodial chemotypes. Hits from thiadiazine and pyrimidine azepine chemotypes were subsequently prioritized for resistance selection studies, yielding distinct mutations in P. falciparum cytochrome b, a validated antimalarial drug target. The thiadiazine chemotype was subjected to an initial medicinal chemistry campaign, yielding a metabolically stable analog with sub-micromolar potency. Our qHTS methodology and resulting dataset provides a large-scale resource to investigate Plasmodium liver and asexual blood stage parasite biology and inform further research to develop novel chemotypes as causal prophylactic antimalarials.

This study focuses on the fabrication and characterisation of single-walled carbon nanotube (SWCNT) buckypapers and polyethersulfone (PES) flat-sheet membranes using Cyrene, aiming toevaluate its efficacy as a green solvent for these applications. Pristine SWCNTs were dispersed inCyrene without surfactants and compared to N-Methyl-2-pyrrolidone (NMP) dispersions. Buckypapers were fabricated from these dispersions and characterised using Scanning ElectronMicroscopy (SEM), Atomic Force Microscopy (AFM), and infrared spectroscopy. Their performancewas tested in wastewater and oil-water emulsion filtrations and antimicrobial activity. PESmembranes incorporating SWCNTs were prepared using phase inversion and analysed via SEM,optical microscopy, and contact angle. Membrane properties and water permeability were assessed,and bacterial challenge tests evaluated antimicrobial activity. Cyrene enabled the dispersion ofSWCNTs at higher concentrations (0.038 mg mL⁻1) compared to NMP (0.013 mg mL⁻1). Transmission Electron Microscopy (TEM) analysis revealed that Cyrene effectively debundles SWCNTs, yielding better dispersion. Buckypapers fabricated with Cyrene demonstrated dense, uniform networks with enhanced surface smoothness and promising filtration performance for wastewater treatment and oil-water separation. PES membranes made with Cyrene exhibited well-organised finger-like structures, interconnected pores, superior porosity, and higher water permeability than NMP-based membranes. Incorporating SWCNTs further improved membrane performance. However, bacterial challenge tests indicated no significant antimicrobial activity. The findings highlight Cyrene’s potential as a sustainable alternative to traditional solvents, offering improved material properties and filtration performance. Despite these advantages, further studies are necessary to address solvent residuals and long-term safety considerations, ensuring its suitability for broader applications.

A more sustainable dialysis and water filtration membrane has been developed, by using the new, safer, bio-based solvent Cyrene® in place of N-methyl pyrrolidinone (NMP). The effects of solvent choice, solvent evaporation time, the temperature of casting gel, and coagulation bath together with the additive concentration on porosity and pore size distribution were studied. The results, combined with infrared spectra, SEM images, porosity results, water contact angle (WCA), and water permeation, confirm that Cyrene® is better media to produce polyethersulfone (PES) membranes. New methods, Mercury Intrusion Porosimetry (MIP) and NMR-based pore structure model, were applied to estimate the porosity and pore size distribution of the new membranes produced for the first time with Cyrene® and PVP as additive. Hansen Solubility Parameters in Practice (HSPiP) was used to predict polymer-solvent interactions. The use of Cyrene® resulted in reduced polyvinylpyrrolidone (PVP) loading than required when using NMP and gave materials with larger pores and overall porosity. Two different conditions of casting gel were applied in this study: a hot (70°C) and cold gel (17°C) were cast to obtain membranes with different morphologies and water filtration behaviours.

This work reports on the use of a bench-scale chemostat (CSTR) in continuous mode and of a pilot-scale membrane bioreactor (MBR) in fed-batch mode to intensively produce acetic and butyric acids using C. butyricum grown on synthetic media. These studies were then used to perform a cost estimation study of the MBR system to assess the potential economic impact of this proposed methodology, regarding the production of carboxylic acids. The MBR system was found to be highly productive, reaching 37.88 g L−1 h−1 of acetic and 14.44 g L−1 h−1 of volumetric cell productivity, favoring acetic acid production over butyric acid at a ratio of 3 moles to 1. The cost of preparation and production of carboxylic acid using this system was found to be 0.0062 £PS/kg with up to 99% carbon recovery.