Merck (Germany)

Fluorosurfactants are an integral part of many industrial processes due to their unparalleled surface activity and high water and oil repellency and can be found in a wide range of consumer products. However, their lack of biodegradability causes great environmental concern and has led to increased regulatory action in recent years. In the search for alternatives, perfluoropropyl vinyl ether was recently identified as a promising building block with an improved ecological profile regarding degradation and accumulation. Here, we utilized short-chain perfluoropropyl vinyl ether (PPVE) or perfluoromethyl vinyl ether (PMVE) as precursors to construct polyether-based fluorosurfactants through copolymerization with hydrophilic comonomers. Surfactant properties and overall fluorine content per molecule could be easily adjusted by changing the comonomer feed. The surface activity was investigated in aqueous solution via tensiometry and was found to be competitive with both legacy PFAS such as perfluorooctanesulfonic acid and current state-of-the-art small molecule fluorosurfactants (γstat ≥ 20.35 mN m–1). These findings illustrate the potential of amphiphilic copolymers as a modular, straightforward, and versatile platform for next-generation fluorosurfactants as an alternative to long-chain legacy PFAS.

Ionic liquids (ILs) composed of the 1-ethyl-3-methylimidazolium [EMIm]+, 1-butyl-3-methylimidazolium [BMIm]+, or butylmethylpyrrolidinium [Pyr14]+ cation and fluorophosphate anions with three, two, or one pentafluorethyl substituents bonded to phosphorus [mer-(C2F5)3PF3]- (FAP3), [trans-(C2F5)2PF4]- (FAP2), and [(C2F5)PF5]- (FAP1) were synthesized from tris(pentafluorethyl)difluorophosphorane. The FAP ILs were characterized by NMR, IR, and Raman spectroscopy and elemental analysis and the single crystal structures of [EMIm]+ ILs with the anions FAP3, FAP2, and FAP1 and of [BMIm]FAP1 were elucidated. The thermal, physicochemical, and electrochemical properties of the ionic liquids were investigated. [BMIm]FAP2 has the lowest dynamic viscosity and the highest specific conductivity among the series of [BMIm]+ ILs making it a promising IL for different applications. The interpretation of the data was aided by results from density functional theory (DFT) calculations. Evaluation of structural, spectroscopic, and theoretical data showed the weakly coordinating nature of the series of phosphate anions to increase in the order of [PF6]- < FAP1 < FAP2 < FAP3. The influence of the size, shape, flexibility and the coordinative behavior of the three FAP anions and the hexafluorophosphate anion on the ionic liquid properties was assessed.

The use of additive manufacturing for rapid prototyping of near-infrared and terahertz components provides seamless and error-free production. This article discusses the additive manufacturing and post-processing of axicons and their performance evaluation using attenuation and near-field-measurements based fundamental techniques. The axicons are manufactured using the materials cyclic olefin copolymer (TOPAS) and polymethyl methacrylate (PMMA), for their respective use in terahertz and near-infrared applications. The optical and terahertz components manufactured using traditional 3D-printing processes, e.g., fused filament fabrication or stereolithography apparatus exhibit high surface roughness in the range of 15 ± 2.5 µm, resulting in undesired propagation and scattering in the near infrared wavelengths. This research work proposes an economical post-processing technique for additively manufactured terahertz and near-infrared axicons for applications in multispectral characterization, e.g., bio-sensing. The authors used an enhanced method of dip-coating, which involves interval dipping and intermittent hardening to achieve better surface finish. An emphasis is placed on interval dipping and intermittent hardening, which lead to excellent transparency in case of additively-manufactured near-infrared axicons. The dip-coated samples exhibit surface roughness below 10 nm. With the use of heated resin material as the coating layer, due to reduced viscosity, the resin material distributes uniformly over the surface of the 3D-printed terahertz and near-infrared axicons. The authors also observed that the DOF length deviation between unprocessed and enhanced dip-coated axicons remains within the measurement error estimation from analytical calculations. In addition to the improved surface finish and transparency, the coatings are also closely matched in refractive index to the axicon material. Such post-processed axicons pave the way for producing a wide array of systems in the fields of communication, imaging, and bio-sensing.

A new one-pot synthesis of 1,3-divinylimidazolidin-2-one (DVI) starting from cheap and commercially available substances, i.e., di(chloroethyl)amine and phosgene or triphosgene was developed. The two-step procedure provides a convenient access to DVI in high purity and good yield without the application of any catalytic system. Additionally, an alternative route that relies on the utilization of carbon dioxide for the preparation of DVI was assessed.

A focus group organised by the Drug Safety Research Unit (DSRU) International Working Group (IWG) on New Developments in Pharmacovigilance discussed current challenges and opportunities in pharmacovigilance (PV), emphasising the need for a multimodal approach in data analysis and accessibility of diverse data sources for drug safety surveillance. Nine participants, selected purposefully for their multisectoral expertise in PV, discussed the value of various data types, including data from clinical trials and real-world data (RWD), each offering distinct strengths and limitations. Key challenges identified included data standardisation, quality variability, technological barriers and ethical concerns, particularly with data derived from social media. Emerging tools such as knowledge graphs were highlighted for their potential to enhance data integration and signal detection, however further research is required. The group also addressed disparities in data access, with particular attention to regulatory restrictions, limited infrastructure in low-resource settings and restricted access to industry-held data. Proposed solutions included fostering greater data transparency, establishing secure data-sharing platforms and forming collaborative consortia to facilitate responsible and ethical data use. Overall, the discussion underscored the need for improved integration, access and methodological rigour to strengthen PV practices and enhance global drug safety monitoring.

Characterization of protein-ligand interactions is essential for the pre-clinical development of drug candidates and Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) has emerged as a valuable tool in this process. HDX-MS has predominantly been employed with high affinity compounds with only a few examples of its application for weaker binders such as fragments. Nevertheless, HDX-MS usage could be instrumental in Fragment-Based Drug Discovery (FBDD) programs. In this work, the drug-target protein Cyclophilin D (CypD) was used as a model to explore the boundaries of fragments binding characterization by HDX-MS (fHDX-MS). We performed a systematic study on the optimal conditions for fHDX-MS execution and found that fragments with binding affinities in the double-digit mM range are still amenable to fHDX-MS. We observed that, despite the intrinsic low resolution of HDX-MS, fragments binding sites that partially overlap can still be distinguished. Overall, this study shows that fHDX-MS can be a useful method for FBDD.

We report here the upcycling of PET (polyethylene terephthalate) waste via semihydrogenation to make ethyl 4‐(hydroxymethyl)benzoate. The reaction is catalyzed by a ruthenium pincer catalyst at 80 °C in bioderived solvents – a combination of 2‐methyl THF and ethanol. A detailed mechanistic investigation through organometallic and kinetic studies, as well as chemical exchange saturation transfer (CEST) NMR spectroscopy, provides insights into the nature of active species and factors that promote and inhibit the catalytic hydrogenation of PET. Using this mechanistic knowledge, a record high turnover number of >30 000 was achieved for the hydrogenative depolymerization of end‐of‐life PET waste (e.g., bottles and textiles). The semihydrogenation product, ethyl 4‐(hydroxymethyl)benzoate, was utilized to make precursors of various known pharmaceutical drugs, an agrochemical, as well as a new and recyclable polyester. A cradle‐to‐gate life cycle assessment demonstrated that using PET waste as a feedstock for EHMB production significantly reduces the environmental footprint compared to the conventional route from p‐toluic acid.

Accurately measuring compound binding affinities is key to driving the pharmaceutical development process. Rigorous physics-based in silico approaches, particularly alchemical free energy methods, have become a gold standard tool for estimating compound affinity changes. Here we present the results of a large-scale pre-competitive collaborative assessment of relative binding free energy (RBFE) calculations generated by 15 pharmaceutical companies. We evaluate an open-source and MIT licensed RBFE Protocol from the Open Free Energy (OpenFE) ecosystem across both public and blinded private datasets, encompassing over 1,700 ligands in total. For the public dataset, the weighted RMSE across the 58 systems was 1.73 [1.53, 1.96] kcal/mol, with 10 of the systems reaching sub-kcal/mol accuracy. For the private dataset, the weighted RMSE across the 37 systems was 2.44 [1.94, 3.06] kcal/mol, with only 2 of the systems reaching sub-kcal/mol accuracy, reflecting the increased complexity of real-world drug discovery. The protocols performance was system-dependent, with no single dominant error source, indicating that accuracy is primarily influenced by input quality and transformation type. Overall, these benchmark results are encouraging and indicate that OpenFE is ready for large-scale industrial applications, with an "out-of-the-box" accuracy that approaches that of commercial solutions. While comparison against published FEP+ results, which were obtained after manual parameter optimization, shows comparable ranking statistics, a gap remains in error statistics, for which we outline possible paths toward improvement. The protocol meets key criteria required for production use in an industrial setting: it shows robust performance, generates reproducible results, and achieves both sufficient throughput and rapid convergence.