London Biofoundry

This article presents an advanced iteration of the polyoxometalate (POM)‐Ionosolv concept to generate biobased methyl formate in high yield and a bleached cellulose pulp from lignocellulosic biomass in a single‐step operation by using redox‐balanced POM catalysts and molecular oxygen in alcoholic ionic liquid (IL) mixtures. The performance of the three Ionosolv‐ILs triethylammonium hydrogen sulfate ([TEA][HSO4]), N,N‐dimethylbutylammonium hydrogen sulfate ([DMBA][HSO4]), and tributylmethylphosphonium methyl sulfate ([TBMP][MeSO4]), mixed with methanol (MeOH) (30/70 wt%), is evaluated by methyl formate yield from extracted hemicellulose and lignin as well as purity of the bleached cellulose pulp in the presence of various Keggin‐type POMs. The redox‐balanced H8PVMnMo10O40 POM catalyst in [TBMP][MeSO4]/MeOH emerge as the most effective combination, achieving 20% methyl formate yield from commercial beech wood. The glucan content in the bleached cellulose‐enriched solid consisted is over 90%, demonstrating that the use of MeOH drastically improved lignin extraction in parallel with full hemicellulose extraction. The cellulose is highly susceptible to enzymatic hydrolysis, generating a pure and concentrated cellulosic glucose stream. The formed solid catalyst complex is examined in detail to reveal its chemical nature as POM‐IL‐complex. The approach is applicable to disparate types of lignocellulosic biomass, including hardwood, softwood, and grass.

Abstract AIMS Gliomas and other primary brain tumours remain a significant cause of cancer-related mortality, with lim- ited predictive biomarkers to guide therapy selection. The PEAR-GLIO trial investigates Pear Bio’s AI-driven ex vivo platform to evaluate the therapeutic sensitivity of FDA-approved and experimental treatments on patient- derived 3D immune-microtumours. This observational study aims to validate the platform’s ability to provide actionable insights for patient stratification and treatment optimisation. The trial also integrates patient and public involvement (PPIE) to improve study design and accessibility. METHODS PEAR-GLIO (NCT06038760) is a UK-based observational study enrolling 50 patients with operable primary brain tumours, including grades 2-4 gliomas. Inclusion criteria include histologically confirmed malignancy, avail- ability of ≥0.4g of tumour tissue and 40mL of whole blood, and consent for sample and data use. Patients re- ceiving pre-surgical chemotherapy or radiotherapy within 30 days or with inoperable disease are excluded. Tumour-derived and immune cells are co-cultured as physiologically relevant 3D immune-microtumours and exposed to FDA-approved and experimental treatments. Phenotypic and molecular responses, including changes in tumour viability, cell death, migration, and immune cell infiltration, are assessed using live imag- ing and computer vision. Real-time confocal imaging and omics analyses evaluate drug mechanisms of action, correlating responses with biomarkers like MGMT methylation, IDH mutation, and 1p/19q co-deletion. RESULTS Recruitment began in October 2023, with 12 patients enrolled to date. Data from the first cohort will guide plat- form optimization and scalability. All samples are anonymised, with outcomes monitored per RANO guidelines. CONCLUSION Early PPIE efforts have enhanced trial design. The platform is concurrently being validated in other high- unmet-need indications, including early-stage breast cancer (NCT05435352) and metastatic kidney cancer (NCT06264479), aiming to advance precision treatment selection and transform clinical oncology.

Metal‐organic cages (MOCs) are a class of self‐assembled materials with promising applications in chemical purifications, sensing, and catalysis. Their potential is, however, hampered by challenges in the targeted design of MOCs with desirable properties. MOC discovery is thus often reliant on trial‐and‐error approaches and brute‐force manual screening, which are time‐consuming, costly, and material‐intensive. Translating the synthesis and property screening of MOCs to an automated workflow is therefore attractive, to both accelerate discovery and provide the datasets crucial for data‐led approaches to accelerate MOC discovery and to realize their targeted properties for specific applications. Here, an automated workflow for the streamlined assembly and property screening of MOCs was developed, incorporating automated high‐throughput screening of variables pertinent to MOC synthesis, data curation and automated analysis, and development of a host–guest assay to rapidly assess binding behavior. Computational modelling supplemented this automated experimental workflow for post priori rationalization of experimental outcomes. This study lays the groundwork for future large‐scale MOC screening: from a relatively modest screen of 24 precursor combinations under one set of reaction conditions, 3 clean MOC species were identified, and subsequent screening of their host–guest behavior highlighted trends in binding and the identification of potential applications in molecular separations.

Antimicrobial resistance is one of the biggest globalhealthcarechallenges. Therefore, there is an urgent need to develop new moleculesthat display distinct antibacterial properties to overcome resistance.With this aim, we have developed a combinatorial and semiautomatedplatform to synthesize and screen a library of 78 compounds againstGram-positive and Gram-negative bacteria. This library is based onoctahedral iridium(III) complexes with general formula [Ir(CN)2(NN)]Cl (where CN are cyclometallatingpolyaromatic ligands and NN are phenanthroline-imidazoleor dipyridophenazine derivatives) which are known to generate reactiveoxygen species (ROS) upon light irradiation. From the initial screenof the entire library (in the dark and under light irradiation) against Escherichia coli and Staphylococcusaureus, we show that this scaffold is highly effectiveat inhibiting growth of Gram-positive bacteria at an intermediatedose (16 μg/mL), displaying a hit rate of >30% in the darkandrising to 56% under light irradiation. Six complexes were selectedfor further studies against a panel of five Gram-positive strains,allowing us to identify two lead complexes with MICs as low as 2 μg/mL.These complexes were studied in more detail to establish their modeof action using a time-kill study against the S. aureus USA300 strain.

Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0] butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one-pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N-modification instills a broad range of strain-release reactivity; ii) sp2-cross-coupling reactions on aryl-BCB-sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine-labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.

Fossil fuel combustion generates nitrogen oxides (NO + NO2 = NOx), which pose threats to the environment and human health. Although commercial products containing titanium dioxide (TiO2) can remedy NOx pollution by photocatalysis, they only function in the ultraviolet (UV). On the other hand, bismuth oxybromide (BiOBr) is active in the visible. BiOBr is stable, affordable, and non-toxic, making it an appealing alternative. In addition, nanoparticulate Bi metal can further enhance visible light absorption through its surface plasmon properties and charge carrier lifetime by spatially separating charge. In this study, to enhance the visible-light activity of TiO2-based photocatalysts for NOx pollution, a composite of Bi-decorated BiOBr/TiO2 was synthesised using a solvothermal method across varying the Ti/Bi atomic ratio (0.2, 2.2, 4.4, and 6.6), and synthesis duration (6h, 12h, and 18h). The photocatalytic performance of the synthesised composites for NO gas removal was investigated using an adapted ISO method (22197–1:2016). Analysis showed that the preferential growth of the (010) crystal facet in BiOBr and the presence of Bi metal both play an important role in the superior photocatalytic activity seen in our Bi-decorated BiOBr/TiO2 composite. The composites were characterised using X-ray diffraction (XRD), attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR), high-resolution scanning electron microscopy (HR-SEM), UV–Vis diffuse reflectance (DRS) spectroscopy, transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, Brunauer-Emmett-Teller (BET) analysis, thermogravimetric analysis (TGA), and diffuse reflectance transient absorption spectroscopy (DR-TAS). Our research shows that the Bi/BiOBr–TiO2 composite synthesised through a 12h solvothermal method with a Ti/Bi atomic ratio of 4.4 exhibits the highest photocatalytic performance towards both NO and NO2 oxidation; with 32.8% and 54.9% NO removal and 15.1% and 29.5% NO2 under visible and UV lamps, respectively.

The oxetane ring is an emergent, underexplored motifin drug discoverythat shows attractive properties such as low molecular weight, highpolarity, and marked three-dimensionality. Oxetanes have garneredfurther interest as isosteres of carbonyl groups and as moleculartools to fine-tune physicochemical properties of drug compounds suchas pKa, LogD, aqueous solubility, andmetabolic clearance. This perspective highlights recent applicationsof oxetane motifs in drug discovery campaigns (2017–2022),with emphasis on the effect of the oxetane on medicinally relevantproperties and on the building blocks used to incorporate the oxetanering. Based on this analysis, we provide an overview of the potentialbenefits of appending an oxetane to a drug compound, as well as potentialpitfalls, challenges, and future directions.

Porous graphdiynes are a new class of porous two-dimensional materials with tunable electronic structures and various pore structures. They have potential applications as well-defined nanostructured electrodes and could provide ideal platforms for understanding energy storage mechanisms underlying supercapacitors. Herein, we investigate the effect of stacking structure and metallicity on energy storage with such electrodes. Simulations revealed that supercapacitors based on porous graphdiynes of AB stacking structure could achieve both higher double-layer capacitance and ionic conductivity than AA stacking. This phenomenon is ascribed to more intense image forces in AB stacking, leading to a breakdown of ionic ordering and the formation of effective "free ions". Macroscale analysis shows that doped porous graphdiynes could deliver both outstanding gravimetric and volumetric energy and power densities due to their enhanced quantum capacitance. These findings pave the way for designing high-performance supercapacitors by regulating pore topology and metallicity of electrode materials. This article is protected by copyright. All rights reserved.

A general approach to 3-azabicyclo[3.1.1]heptanes by reduction of spirocyclic oxetanyl nitriles was developed. The mechanism, scope, and scalability of this transformation were studied. The core was incorporated into the structure of the antihistamine drug Rupatidine instead of the pyridine ring, which led to a dramatic improvement in physicochemical properties.