Journal: ChemRxiv

Abbreviation

Publisher

Cambridge University Press

Journal Volumes

ISSN

2573-2293

Description

Filters

2021 - 202627
Reset filters

Search Results

Publications1 - 10 of 27
  • Room temperature NO2 chemiresistive sensing with porous WS2 films
    Item type: Working Paper
    Hersberger, Simone; Pereira Martins, Michael; Fassbind, Selina; et al. (2025)
    ChemRxiv
    Nitrogen dioxide (NO2) is a hazardous air pollutant with a lowered annual mean exposure limit from 40 to 10 µg/m3 (~5 parts-per-billion by volume, ppb) by the World Health Organization in 2021. This motivates the exploration of low-power and cost-efficient sensors that can detect such low concentrations of NO2, exhibit high selectivity against interfering analytes and resilience to humidity fluctuations. Here, a selective, stable and humidity-robust sensor for NO2 sensing at room temperature is presented. Flame-aerosol deposition followed by dry sulfidation results in highly porous (98%) and nanostructured WS2 films. These films exhibit a fivefold increase in response and over an order-of-magnitude reduction in response time, compared to conventional spin-coated films. Remarkable sensing performance down to 1 ppb of NO2 (with a signal-to-noise ratio of 12.9) is achieved with high selectivity (>164) towards environmental interferents including NH3, NO, acetone, H2S, benzene, CO, ethanol, methanol, N2O and toluene. We also reveal high robustness (response change ± 18%) against varying relative humidity (0 – 90%) and response stability over more than 6 months (± 10%). This sensor outperforms previously reported NO2 sensors operating at room temperature, making it well-suited for integration into devices for environmental monitoring or wearables for personal exposure assessment.
  • Efficient Multistate Free-Energy Calculations with QM/MM Accuracy using Replica-Exchange Enveloping Distribution Sampling
    Item type: Working Paper
    Pregeljc, Domen; Hügli, Ramon; Riniker, Sereina (2025)
    ChemRxiv
    Calculating free-energy differences using molecular dynamics (MD) simulations is an important task in computational chemistry. In practice, the accuracy of the results is limited by model approximations and insufficient phase-space sampling due to limited computational resources. In the present work, we address these challenges by integrating the quantum-mechanical/molecular-mechanical (QM/MM) scheme with replica-exchange enveloping distribution sampling (RE-EDS) to obtain a multistate and multiscale free-energy method with high computational efficiency. The performance of QM/MM RE-EDS is showcased by calculating hydration free energies for three datasets using semi-empirical methods for the QM zone. We highlight the importance of the choice of QM Hamiltonian and the effect of the compatibility between the QM and MM models. Especially the choice of semi-empirical method has a substantial effect on the accuracy compared to experiment, but also the choice of MM water model is non-negligible. Our findings indicate that RE-EDS is an efficient approach for calculating free-energy differences with a QM/MM scheme, and lays the foundation for future developments and applications.
  • Development of a Universal NADH Detection Assay for High Throughput Enzyme Evolution Using Fluorescence Activated Droplet Sorting
    Item type: Working Paper
    Kolaitis, Gerassimos; Jain, Ankit; Romeis, Dennis; et al. (2022)
    ChemRxiv
    Directed evolution is an enzyme engineering approach based on the generation and screening of large mutagenesis libraries, with a view to discovering enzymes with improved properties such as activity, specificity or stability. Recently, droplet-based microfluidics has emerged as a powerful technology enabling ultra-high throughput screening of enzyme libraries and the effective identification and isolation of novel, improved enzyme variants, outperforming conventional enzyme screening platforms by several orders of magnitude in terms of speed and chemical consumption. When using droplet-based platforms fluorescence remains the predominant choice for detection of enzymatic activity due to its high sensitivity and low limits of detection. However, this approach often requires the use of labeled, non-natural substrates, which are typically not commercially available. In addition, fluorescence detection is only suitable for a few enzyme classes such as hydrolases or oxidases, whose reactions can often lead to a fluorescent signal. Herein, we describe an assay that enables fluorescence detection of enzymatic activity through a reaction cascade for the industrially important enzyme subclass of dehydrogenases. By applying a hydrogen peroxide-forming NADH oxidase coupled with peroxidase-catalyzed fluorescence generation, quantification of NADH and dehydrogenase activity becomes possible. We explored the utility of this assay in the evolution of a low performing alcohol dehydrogenase from Sphingomonas species A1 (SpsADH). A fluorescence-activated droplet sorting (FADS) platform was utilized for the screening of a 50,000 variant SpsADH library towards the non-native substrate L-guluronate, a primary component of macroalgae, with the potential to serve as raw material for the bio-based production of chemicals. Significantly, we found an enzyme variant with a 2.6-fold improvement in catalytic efficiency kcat/Km towards the non-native substrate, with only a single round of mutagenesis. The screening of SpsADH libraries confirms the ability of the developed method to enrich active enzyme variants.
  • Simulation of Aqueous Solutes Using the Adaptive Solvent-Scaling (AdSoS) Scheme
    Item type: Working Paper
    Kubincová, Alzbeta; Riniker, Sereina; Hünenberger, Philippe Henry (2023)
    ChemRxiv
    The Adaptive Solvent-Scaling (AdSoS) scheme [J. Chem. Phys. 155 (2021) 094107] is an adaptive-resolution approach for performing simulations of a solute embedded in a fine- grained (FG) solvent region surrounded by a coarse-grained (CG) solvent region, with a continuous FG↔CG switching of the solvent resolution across a buffer layer. Instead of relying on a distinct CG solvent model, AdSoS is based on CG models defined by a dimensional scaling of the FG solvent by a factor s, accompanied by the s-dependent modulation of its mass and interaction parameters. The latter changes are designed to achieve an isomorphism between the dynamics of the FG and CG models, and to preserve the dispersive and dielectric solvation properties of the solvent with respect to a solute at FG resolution. As a result, the AdSoS scheme minimizes the thermodynamic mismatch between the different regions of the adaptive-resolution system. The present article generalizes the scheme initially introduced for a pure atomic liquid in slab geometry to more practically relevant situations involving: (i) a molecular dipolar solvent (e.g. water); (ii) a radial geometry (i.e. spherical rather than planar layers); and (iii) the inclusion of a solute (e.g. water molecule, dipeptide, ion or ion pair).
  • Prospects of Nanoparticle-based Radioenhancement for Radiotherapy
    Item type: Working Paper
    Gerken, Lukas; Gerdes, Maren; Pruschy, Martin; et al. (2023)
    ChemRxiv
    Radiotherapy is a key pillar of solid cancer treatment. Despite high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs-at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the fundamental knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.
  • Unraveling Torsional Preferences: Comparative Analysis of Torsion Motif Angle Distributions Across Different Environments
    Item type: Working Paper
    Braun, Jessica; Katzberger, Paul; Landrum, Gregory; et al. (2025)
    ChemRxiv
    Understanding the conformational ensemble of molecules in different environments is at the core of many research efforts. In conformer generation and geometry optimization, the complexity of the conformer space arises from the underlying torsion-angle distributions, which, in the case of force fields and some in silico conformer generators like ETKDG, are derived from accumulated torsion profiles for a predefined set of torsion motifs (termed "torsion motif angle distributions", TMADs). Comparative studies of conformer generation and global optimization algorithms often neglect that the TMADs are sensitive to the environment they are extracted from, leading to comparisons of conformational ensembles and minimum-energy conformations from e.g. crystal versus vacuum environments. Here, we present a large-scale comparative study of TMADs across different environments, namely crystal, vacuum, water, and hexane. Our results show that the effects in the different environments, such as solvent-solute interactions in water and hexane, and packing effect in the crystal, produce strikingly distinct torsion distributions for most of the selected torsion motifs. In addition to qualitative and quantitative comparison of the extracted TMADs, we also provide an automated fitting procedure that allows rapid parameterization of the distributions. These newly found parameters can be employed in a solvent-specific conformer generation procedure in the future.
  • Exploring protein-ligand binding affinity prediction with electron density-based geometric deep learning
    Item type: Working Paper
    Isert, Clemens; Atz, Kenneth; Riniker, Sereina; et al. (2023)
    ChemRxiv
    Rational structure-based drug design relies on accurate predictions of protein-ligand binding affinity from structural molecular information. Some of the existing deep learning approaches for this purpose have been criticized for insufficiently capturing the underlying physical interactions between ligands and their macromolecular targets. Herein, we propose to include bond-critical points based on the electron density of a protein-ligand complex as a fundamental physical representation of protein-ligand interactions. Employing a geometric deep learning model, we explore the usefulness of these bond-critical points to predict absolute binding affinities of protein-ligand complexes, benchmark model performance against existing methods, and provide a critical analysis of this new approach. The models achieved root-mean-squared errors of 1.4-1.8 log units on the PDBbind dataset, and 1.0-1.7 log units on the PDE10A dataset, not indicating significant advantages over benchmark methods. The relationship between intermolecular electron density and corresponding binding affinity was analyzed, and Pearson correlation coefficients r > 0.7 were obtained for several macromolecular targets.
  • Electrocatalytic metal hydride generation using concerted proton electron transfer mediators
    Item type: Working Paper
    Dey, Subal; Masero, Fabio; Brack, Enzo; et al. (2021)
    ChemRxiv
    The electrochemical generation of metal hydride (M H) species remains one of the major hurdles for a wide range of catalytic reactions to be carried out electrochemically. We introduce here a new strategy for electrocatalytic M H generation using concerted proton electron transfer (CPET) mediators. We investigate the combination of a series of CPET mediators with the CO2 electroreduction catalyst [MnI(bpy)(CO)3Br] (bpy = 2,2’-bipyridine), probing the reversal of the product selectivity from CO to HCOOH to evaluate the efficiency of the M H generation step. We demonstrate the formation of the manganese-hydride by in-situ spectroscopic techniques and determine the thermodynamic boundary conditions for this mechanism to occur. A synthetic iron-sulfur cluster is identified as the best CPET-mediator for that system, enabling the preparation of a benchmark catalytic system for HCOOH generation.
  • Branch-selective Olefin Hydroaminoalkylation from Ti(III)–Al Bimetallic Intermediates evidenced by EPR Hyperfine Spectroscopy and DFT Calculations
    Item type: Working Paper
    Inoue, Mariko; Stropp, Julian; Ashuiev, Anton; et al. (2024)
    ChemRxiv
    Stereoselective hydroaminoalkylation of alkenes via α-C–H bond activation of alkylamines is an efficient process for the preparation of complex alkylamines minimizing stoichiometric waste. Herein, we report that a combination of Cp*TiMe3 and AlMe3 catalyzes the branch-selective hydroaminoalkylation of 1-alkenes, including styrene derivatives and 1,3-dienes, with N-methylaniline derivatives. Kinetic studies reveal that the active species are generated from in situ generated Cp*TiMe2(NMePh) and alkylaluminum. Continuous wave (CW) and pulse EPR spectroscopy show that multiple Ti(III) species, bearing amido and most probably alkyl ligands as well as an Al center, are formed, paralleling catalytic activity. Based on these findings complemented by DFT studies, we propose a reaction mechanism featuring d1 Ti(III) three-membered azatitanacycle species with amidoaluminate anions as active species. The alkene insertion into the Ti–C bond of the three-membered metallacycle intermediate is a key step that drives selectivity. This step favors the branched product through both steric and electronic effects, namely by i) minimizing steric repulsion between the styrene phenyl ring and the Cp*/Al moieties and ii) spin delocalization from metal to substrate antibonding orbital, which stabilizes the transition state resulting in facile insertion into M–C bond.
  • Peptide-Directed Attachment of Hydroxylamines to Specific Lysines of IgG Antibodies for Bioconjugations with Acylboronates
    Item type: Working Paper
    Tanriver, Matthias; Müller, Marco; Richards, Daniel; et al. (2023)
    ChemRxiv
    The role of monoclonal antibodies as vehicles to deliver payloads has evolved as a powerful tool in cancer therapy in recent years. The clinical development of therapeutic antibody-conjugates with precise payloads holds great promise for targeted therapeutic interventions. The use of affinity-peptide mediated functionalization of native off-the-shelf antibodies offers an effective approach to selectively modify IgG antibodies with a drug antibody ratio (DAR) of 2. Here, we report the traceless, peptide-directed attachment of two hydroxylamines to native IgGs followed by chemoselective KAT ligation with quinolinium acyltrifluoroborates (QATs), which provide enhanced ligation rates with hydroxylamines under physiological conditions. By applying KAT ligation to the modified antibodies, conjugation of small molecules, proteins, and oligonucleotides to off-the-shelf IgGs proceeds efficiently, in good yields, and with simultaneous cleavage of the affinity peptide-directing moiety.
Publications1 - 10 of 27