The covalent engineering of cellular surfaces with synthetic polymers can introduce abiotic functionality, deliver cargoes to cell surfaces and modulate cell-cell interactions. Metabolic oligosaccharide engineering (MOE) has emerged as a particularly versatile and powerful tool to install chemo-selective handles onto the cell-surface glycocalyx to capture macromolecular ligands. Here we explore the impact of both polymer molecular weight and the specific glycan label on the efficiency of the grafting-to reaction of alkyne-terminated polymers to azidolabelled glycans. Azido,N-acetyl -glucosamine/-galactosamine and -mannosamine were used to label both adherent and suspension mammalian cells, to vary the glycan-location of the azide handle at the cellular surface. Using flow cytometry we show that the location of the azide within the glycan impacts the extent of polymer capture, with the more exposed sialic-acid azide labels giving the highest grafting. Higher molecular weight polymers showed less glycan-dependant capture than smaller, suggesting the polymer steric constraints, rather than glycan location, was the limiting factor for larger cargoes. These results will guide the development of cell/ polymer hybrids with tuneable function and potentially tuneable lifetimes, unlocking opportunities in cell-based therapies.

An important property of the compounds comprising organic aerosol is volatility, typically described in terms of saturation vapor pressure or saturation concentration (measured in µg/m3). The volatility of aerosol constituents can be estimated based on their molecular formula using different parametrizations or measured experimentally by using a chemical ionization mass spectrometer (CIMS) coupled to a filter inlet for gases and aerosols (FIGAERO). In this technique, aerosol sample is collected semi-online and evaporated via gradually heated nitrogen flow desorbing organic constituents to be measured by CIMS. From the temperature at which detected chemical species reach their maximum signal, it is possible to determine the respective compositions’ volatility.In 2024, the FIGAERO-CIMS was deployed at the CHANEL (household chemicals amplifying urban aerosol pollution) measurement campaign at the SAPHIR chamber at Jülich Research Centre, Germany. During the campaign, complex reactive mixtures representing urban air scenarios were injected into the chamber, and exposed to both day- and night-time oxidation via opening or closing the roof to natural sunlight. We developed a multi-peak fitting algorithm to fully fit each composition’s thermogram (signal vs. desorption temperature), resulting in multiple nominal saturation concentrations per detected composition. We interpret these as combinations of simple volatility-driven desorption and decomposition (typically at higher temperatures) of larger compounds, such as accretion products.We tracked the chemical composition and volatility of secondary organic aerosol throughout its formation and subsequent aging in the chamber over several hours. The chemical composition measured by FIGAERO-CIMS was compared with other co-located online mass spectrometric techniques, e.g., CIMS following online aerosol evaporation by a heated sheath flow (WALL-E). Our initial results show how aerosol volatilities typically decreased with age, as more oxygen was incorporated. Further, night-time conditions resulted in both increased organonitrate formation and lower product volatility relative to day-time conditions.

As the global rise in antimicrobial resistance calls for new therapeutic strategies, synthetic antimicrobial polymers (SAMPs) have emerged as promising alternatives to host-defense peptides, offering tunable structures and reduced limitations. In this work, we employed machine learning (ML) approaches to elucidate the structure-activity relationships of a library of polyacrylamides systematically varied in (1) amine side-chain chemistry, (2) chain length, (3) cationic amine ratio, and (4) polymer architecture. The library consisted of 23 different polymer designs, 3 of which exhibited low minimum inhibitory concentrations (MIC) against different bacterial strains, and 5 of which caused low red blood cells agglutination. Among the evaluated ML algorithms, regression random forest and gradient boosting regression consistently reproduced feature importance and maintained stable decision-tree structures, with gradient boosting outperforming random forest in predictive power. Gradient boosting achieved RSME values of 20, 6, 13 and 12 μg/ml, respectively, for each modelled MIC of 4 bacterial strains: Pseudomonas aeruginosa PA14, Pseudomonas aeruginosa LESB58, Staphylococcus aureus USA300 and Staphylococcus aureus Newman (total data range 64-513 μg/ml). RSME for modelled hemagglutination was 1 μg/ml. Calculation of feature importances and visualisation with beeswarm and waterfall plots highlighted the contribution of individual polymer features through Shapley additive explanations (SHAP). All bacteria strains considered, the type and percentage of cationic monomer are the most important features determining best-performing SAMP designs. Collectively, our findings demonstrate that boosting-ensemble methods offer consistent robust predictive capability and can serve as effective tools for forecasting the potency and toxicity of future SAMP designs, with potential for application in larger, multi-sourced libraries.

Abstract Reversible addition–fragmentation chain transfer (RAFT) polymerization is a key tool in modern macromolecular design. Central to its success is the availability of versatile chain transfer agents (CTAs), typically based on thiocarbonylthio compounds. Herein, we report a refined, scalable, and high-yield synthesis of a family of trithiocarbonate RAFT agents based on a propanoic acid leaving group, mimicking the propagating radical of acrylic acid, which permits efficient mediation of the polymerization of a wide range of monomers. We report the synthesis of 2-{[(butylsulfanyl)carbonothioyl]sulfanyl}propanoic acid (BPTC), commonly known as (Propanoic Acid)yl Butyl TrithioCarbonate (PABTC), a highly oil-soluble derivative, 2-{[(dodecylsulfanyl)carbonothioyl]sulfanyl}propanoic acid (DoPAT), and a highly water-soluble derivative, 3-[[[(1-carboxyethyl)thio]carbonothioyl]thio]propanoic acid (CETCP). By optimizing the aqueous-based reaction conditions, we achieved yields of 80% or higher of high-purity products across all three derivatives on a tens of grams scale, without the necessity of intensive organic solvent extraction or multiple recrystallization steps.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), remains a significant global health challenge. Currently treatment of drug-sensitive TB, involves a six-month regimen consisting of a combination of four anti-TB drugs, with drug-resistant TB requiring over two years of treatment and additional drugs. As toxicity of anti-TB drugs often leads to poor compliance, disease relapse and the emergence of drug-resistant strains, new strategies to reduce drug toxicity and shorten treatment duration are critical. We report nanocarrier-based drug delivery systems targeting macrophages, which primarily support replication and survival of Mtb . We have developed mannose-functionalized nanoparticles that bind to mannose receptors on macrophages and feature a pH-sensitive core which releases an encapsulated drug in the acidic lysosomal environment of macrophages. Rifampicin (RIF), a main anti-TB drug currently in use clinically, was encapsulated within the nanoparticles. We demonstrate that antibiotic-containing nanocarriers efficiently accumulated in macrophages without causing toxicity. Encapsulated RIF showed enhanced efficacy against both BCG and Mtb in primary macrophages. Biodistribution studies in mice revealed that the nanoparticles have extended circulation time and do not induce toxicity. In addition, the encapsulated RIF showed better targeting of mycobacteria when compared to free RIF in a murine model of mycobacterial infection. Such an enhanced bacterial killing using mannose-functionalised nanocarriers loaded with the key anti-TB drug rifampicin offers excellent potential for TB therapy.

Online chemical characterization of atmospheric particles is often challenged by thermal decomposition, fragmentation, wall losses, ionization selectivity, and rapid changes in particle concentration and composition. To resolve these current limitations, we developed the Wall-Free Particle Evaporator (WALL-E) coupled to a chemical ionization mass spectrometer - model Vocus B4 (Bansal et al., 2025). WALL-E enables continuous evaporation of particles to detectable vapors using flash evaporation utilizing a mixture of heated sheath flow as well as a compact thermal desorption region, aiming to preserve fast atmospheric variability while reducing artefacts and decomposition linked to surface interactions by minimizing residence time (Gao et al., 2025). In this work, we present the first ambient field deployment of the WALL-E - Vocus B4 chemical ionization mass spectrometer equipped with an Aim reactor (Riva et al., 2024). Field measurements were conducted from mid-September to mid-October 2025 at the AIRPARIF background supersite named Paris 1er – Les Halles in France.Figure 1: Temporal evolution of the some of the trace gasesThe campaign provides a real-world test of WALL-E performance under highly variable urban conditions. The resulting particle-phase molecular time series captures short-timescale variability alongside sustained background changes. To further identify the main aerosol sources, we applied matrix factorization to the WALL-E–Vocus B4 dataset to resolve distinct composition modes with characteristic temporal signatures. A key outcome is the prominent role of cooking-related emissions, which emerge as a robust factor with clear diurnal structure (enhanced during meal-time periods) and diagnostic molecular features in the particle-phase spectra. The analysis also separates recurring daily patterns from more persistent background/regional influences. Overall, this work provides a compact, interpretable description of urban particle-phase variability in central Paris based directly on online molecular composition.This work was supported by the CLOUD-DOC project (Grant Agreement No. 101073026) under HORIZON-MSCA-2021-DN-01. This work was also supported by the European Research Council (ERC) under the European Union’s Horizon Europe research and innovation program through the Starting Grant CHANEL (Grant Agreement No. 101076276).Bansal, P., et al. “Comprehensive airborne molecular contamination monitoring with single-digit parts-per-trillion sensitivity.” Journal of Micro/Nanopatterning, Materials, and Metrology 24(4), 044003 (30 December 2025). https://doi.org/10.1117/1.JMM.24.4.044003.Gao, L., Zgheib, I., Stergiou, E., Carstens, C., Sari Doré, F., Dupanloup, M., Bourgain, F., Perrier, S., and Riva, M.: Characterization of the newly designed wall-free particle evaporator (WALL-E) for online measurements of atmospheric particles, Atmos. Meas. Tech., 18, 5087–5101, https://doi.org/10.5194/amt-18-5087-2025, 2025.Riva, M., Pospisilova, V., Frege, C., Perrier, S., Bansal, P., Jorga, S., Sturm, P., Thornton, J. A., Rohner, U., and Lopez-Hilfiker, F.: Evaluation of a reduced-pressure chemical ion reactor utilizing adduct ionization for the detection of gaseous organic and inorganic species, Atmos. Meas. Tech., 17, 5887–5901, https://doi.org/10.5194/ , amt-17-5887-2024, 2024.

Liquid crystals (LCs) are a class of materials that combine molecular order and fluidity, making them crucial for technologies from displays to sensors. However, polymeric LC materials typically lack molecular precision, limiting systematic control over their phase behavior. Here, we report a modular synthetic strategy to prepare amphiphilic columnar liquid crystals based on hydrophobic di- and trialkylated galloyl cores attached to a sequence-defined polar oligomer grown by a thiolactone-based iterative protocol. This approach enables independent variation of (i) polar monomer type (e.g., hydroxyethyl acrylate and N,N-dimethylacrylamide), (ii) oligomer length (from 1-mer to tetramer), and (iii) core topology (two or three C18 chains). Differential scanning calorimetry, polarized optical microscopy, and X-ray scattering show that the number of hydrophobic C18 chains on the aromatic core is the dominant parameter governing mesophase stability. Derivatives with three C18 chains exhibit higher melting and isotropization temperatures and more pronounced transitions from lamellar crystals to hexagonally packed columnar mesophases than their two C18 analogues. The chemistry and length of the sequence-defined polar block further tune crystallization and mesophase behavior, i.e. hydrogen-bonding heads increase thermal stability, whereas bulkier PEG-like heads reduce crystallinity and can destabilize mesophases. Increasing oligomer length reduces crystallization enthalpies and can introduce competing liquid-crystalline states. These results demonstrate that the liquid crystalline behavior can be encoded at the molecular level, providing a basis for designing responsive and sequence-programmed LC materials.

Cyclic peptide-polymer conjugates offer a unique biocompatible system with many advantages but come at the cost of being analytically challenging. Developing further analytical techniques of complex polymer-conjugate systems is key to understanding synthetic and medicinal properties. In this contribution, a synthetic cyclic peptide-polymer conjugate is analyzed using electron capture dissociation (ECD), infrared multiphoton absorption dissociation (IRMPD), and 193 nm ultraviolet photodissociation (UVPD) on the same mass spectrometry system. IRMPD and UVPD were shown to effectively characterize unconjugated cyclic peptide species. ECD was less informative during cyclic peptide analysis due to the production of multiple sequence scrambling fragments and radical side chain losses. ECD was shown to produce extensive fragmentation and enable the characterization of conjugated side chains of cyclic species. ECD and IRMPD thus provided complementary data, enabling the target analysis of conjugated systems. UVPD effectively characterized both the cyclic peptide and the conjugating polymer in one experiment, being able to produce complete cyclic peptide fragmentation via b/y fragment pathways and polymer fragmentation via a/x poly(2-ethyl-2-oxazoline) fragment pathways.

The lack of appropriate antimicrobials to tackle multidrug-resistant Gram-negative bacteria poses an escalating threat to modern medicine. Addressing this urgent issue, we have recently developed synthetic nanoengineered antimicrobial polymers (SNAPs), inspired by the physicochemical properties of antimicrobial peptides. Our findings have demonstrated that SNAPs are potent antimicrobial agents characterized by low toxicity and cost-effective large-scale production. In this study, we elucidate the mechanism of action of two distinct SNAPs, which vary in length and charge distribution. Focusing on the Gram-negative pathogen Pseudomonas aeruginosa LESB58, a hypervirulent strain prevalent in cystic fibrosis patients, we employ advanced high-resolution imaging techniques and neutron reflectometry to uncover the precise interactions between SNAPs and the bacterial cell envelope. Our research identifies lipopolysaccharide as a critical target, detailing architecture-specific envelope disruptions, such as asymmetry loss, pore formation, and membrane dissolution. These insights into the structure-function relationships of SNAPs pave the way for the rational design of tailored antimicrobial polymers with specific targeted mechanisms of action.

Self-assembling cyclic peptide nanotubes are fascinating supramolecular systems with promising potential for various applications, such as drug delivery, transmembrane ionic channels, and artificial light-harvesting systems. In this study, we present novel pH-responsive nanotubes based on asymmetric cyclic peptide-polymer conjugates. The pH response is introduced by a tertiary amine-based polymer, poly(dimethylamino ethyl methacrylate) (pDMAEMA) or poly(diethylamino ethyl methacrylate) (pDEAEMA) which is protonated at low pH. The self-assembling behaviour of their corresponding conjugates is investigated using different scattering and spectroscopy techniques. Compared to conjugates with hydrophilic polymeric corona, the introduction of hydrophobic polymer chains on the periphery of the cyclic peptides can prevent water molecules from penetrating through to the peptide rings, allowing the construction of hydrogen bonding interactions between cyclic peptides to form longer nanotubes. The switching between assembly and non-assembly is triggered by the change in the surrounding environmental pH, which process is controlled by the coordination between hydrophobic interactions and electrostatic repulsions. Due to the different hydrophobicity of these two polymers, the self-assembly of their corresponding conjugates varies extensively. We first demonstrate this evolution in detail and describe the relationship between the self-assembly and the inherent properties of grafted polymers, such as polymer compositions, the protonation degree of the responsive polymers and the polymer molecular weight in solutions.

Cyclic peptide-polymer conjugate nanotubes have been shown to be powerful drug delivery vectors, due to their propensity for dynamic self-assembly, high aspect ratio morphology and structural interchangeability. Building upon previous studies that demonstrate the shielding abilities of the polymeric corona of nanotubes to enhance pro-drug bond stabilities and modulate hydrolysis, here the concept of a hydrophobic core building block with multiple drug units to improve drug loading capacity and overall efficiency of the nanotube carriers is utilized. By leveraging the intermolecular features of the drug core to strengthen assembly, it is hypothesized that these nanotubes have the potential as a responsive supramolecular delivery system whereby upon full hydrolysis of the labile drug, these core forming interactions disappear, and nanotubes can fall apart and undergo clearance. Herein, the self-assembly, in vitro efficacy and in vivo pharmacokinetic and anti-tumor pharmacodynamics of these nanotubes in colorectal cancer models, comparing the potent topoisomerase inhibitor SN-38 with its clinically-used parent pro-drug irinotecan, is explored.

The growing drive for sustainable materials has pushed the development of degradable polymers. This work explores the incorporation of alpha-lipoic acid (LA), a commercially available monomer capable of radical ring-opening polymerization (rROP), into polymer backbones using macroRAFT-mediated emulsion polymerization. A series of poly(butyl acrylate) (PBA) seed latexes with increasing LA content (up to 40 mol%) were synthesized and subsequently chain extended with tert-butyl acrylate (tBA) with up to 40 mol% LA and styrene (St) with up to 10 mol% LA to form diblock copolymers. Degradation studies revealed that thermolysis in DMF to cleave the C-S and S-S bonds was significantly more effective than using tris(2-carboxyethyl)phosphine (TCEP) to selectively target the S-S bonds. Substantial molecular weight reduction was observed from low LA mol% incorporation (<10 mol% LA), with minimal additional reduction with increasing mol% LA. Mechanical testing of PBA-b-PSt films demonstrated that at 5 mol% LA incorporation, minimal impact on mechanical properties was observed, while still enabling effective degradation. These findings highlight the potential of LA-based emulsion polymerization systems for producing scalable, degradable polymeric materials suitable for industrial applications such as coatings and adhesives.

Antimicrobial polymers, which have emerged as a promising alternative to antibiotics in the fight against antimicrobial resistance, are based on the design of cationic host defense peptides (CHDPs). Being part of the mammalian innate immune system, CHDPs possess both antimicrobial and immunoregulatory effects to manage bacterial infections. However, the immunomodulatory effects of antimicrobial polymers remain largely unexplored. Within this work, a library of 15 copolymers was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and their abilities to modulate pro-inflammatory pathways in lipopolysaccharide (LPS)-activated murine and human macrophages were investigated. We found that two diblock copolymers with cationic units copolymerized with either apolar or hydrophilic comonomers appeared to have anti-inflammatory activity through suppression of the activation of the nuclear factor kappa-light-chain enhancer of the activated B cell (NF-κB) signaling pathway, scavenging of reactive oxygen species, and reduced production of the pro-inflammatory cytokine interleukin-6 (IL-6). Furthermore, the cationic-apolar copolymer exhibits significant antimicrobial activity against P. aeruginosa. Thus, this promising copolymer holds potential as a dual-action therapeutic, effectively combating bacterial infections while curbing prolonged inflammation and thereby preventing sepsis at the site of infection.

Sébastian Perrier, Youqing Shen, Zhuxian Zhou, Todd Emrick and Marxa L. Figueiredo introduce the Polymer Chemistry themed issue on polymers for gene delivery.

While photochemical aging is known to alter secondary organic aerosol (SOA) properties, this process remains poorly constrained for anthropogenic SOA. This study investigates the photodegradation of SOA produced from the hydroxyl radical-initiated oxidation of naphthalene under low- and high-NOx conditions. We used state-of-the-art mass spectrometry (MS) techniques, including extractive electrospray ionization and chemical ionization MS, for the in-depth molecular characterization of gas and particulate phases. SOA were exposed to simulated irradiation at different stages, i.e., during formation and growth. We found a rapid (i.e. >30 min) photodegradation of high-molecular-weight compounds in the particle-phase. Notably, species with 20 carbon atoms (C20) decreased by 2/3 in the low-NOx experiment which was associated with particle mass loss (∼12%). Concurrently, the formation of oligomers with shorter carbon skeletons in the particle-phase was identified along with the release of volatile products such as formic acid and formaldehyde in the gas-phase. These reactions are linked to photolabile functional groups within the naphthalene-derived SOA products, which increases their likelihood of being degraded under UV light. Overall, photodegradation caused a notable change in the molecular composition altering the physical properties (e.g., volatility) of naphthalene-derived SOA.

Secondary organic aerosols (SOA) have significant effects on visibility1, human health2, and climate3. They are formed from the oxidation of volatile organic compounds (VOCs) in the atmosphere, leading to less volatile oxidation products that can subsequently partition into, or react with existing, aerosol particles.4-5 Biomass burning (BB) is estimated to be the second-largest source of VOCs and the largest source of fine OA globally.6 Extreme fires have been estimated to increase by 30% by 2050, which will greatly increase the concentration of BB VOCs and OA in the atmosphere. While photochemistry and humidity are known to influence SOA formation and aging,7–10 their impacts on BB-SOA remain poorly constrained and should be addressed to better capture the evolution of BB-SOA in the atmosphere.In this work, an oxygenated aromatic BB-marker, i.e., o-cresol (C7H8O), and two types of fuels (South African grass and chaparral from California) were used to study the chemical processes leading to the formation and aging of BB-SOA. The experiments were conducted in simulation chambers at PSI and LISA, respectively. Various oxidants (OH, O3, NO3) and humidity levels were used for these experiments, to explore gas- and particle-oxidation processes. A fast-switching chemical-ionization Orbitrap mass spectrometer, and a Vocus proton-transfer-reaction mass spectrometer were used to characterize gaseous species, while BB-SOA were characterized using an extractive electrospray ionization mass spectrometer, and a newly developed Vocus wall-less aerosol load - evaporator (WALL-E) AIM mass spectrometer. 1 Finlayson-Pitts, B. J. et al. Chemistry of the upper and lower atmosphere: theory, experiments, and applications; Academic Press: San Diego, 2000.2 Nel, A. Science 2005, 308, 804–805.3 Boucher, O. et al. IPCC Report 2013, 571–657.4 Ziemann, P. J. et al. Chem. Soc. Rev. 2012, 41, 6582.5 Srivastava, D. et al. NPJ Clim. Atmos. Sci. 2022, 5, 22.6Akagi, S. K. et al. Atmos. Chem. Phys. 2011, 11, 4039–4072.7 McNeill, V. F. Environ. Sci. & Technol. 2015, 49, 1237–1244.8 Xu, W. et al. Environ. Sci. & Technol. 2017, 51, 762–7709 Kuang, Y. et al. Environ. Sci. & Technol. 2020, 54, 3849–3860.10 Wang, J. et al. Proc. Natl. Acad. Sci. (PNAS), 2021, 118.