Research articles

Microbial natural products are an important source for antibiotic discovery, however, their efficient dereplication remains challenging. Here, the authors develop an analytical pipeline, nanoRAPIDS, to prioritize low abundance bioactive compounds at nanoscale, by integrating the bioassay of interest, automated mass spectrometry identification and GNPS-based dereplication, resulting in the discovery of saquayamycin N from Streptomyces sp. MBT84.

Heterogeneous catalysis that occurs when the anodic and cathodic reactions are short-circuited in an appropriate electrolyte is conceptualized as mixed-potential-driven catalysis, however, its theoretical framework remains underexplored. Here, the authors propose the overpotentials as the driving force of the catalysis and extend Prigogine’s theory to formulate the kinetic equations for the energy conversion from the cathodic and anodic half-reactions into overpotentials, by formation of a mixed potential determined by the catalytic activity.

Highly energetic charge carriers generated in plasmon-assisted electrocatalysis can increase reaction rates and impart novel selectivity trends, but a simple protocol to differentiate between thermal and nonthermal plasmonic contributions is lacking. Here, the authors use cyclic voltammetry and finite element simulations to show direct interband excitation of gold by visible light exclusively enhances current density via photothermal heating, while plasmon excitation leads to photothermal and nonthermal enhancements.

Cobalt-based materials have a wide range of applications from information storage to electromagnetic absorbers in aerospace manufacturing, but the corrosion of cobalt nanosurfaces is poorly explored. Here, the authors combine mass spectrometry and DFT to study gas-phase reactions of Co_n^±/0 (n = 1–30) with water and oxygen and find that only anionic cobalt clusters give rise to water dissociation, whereas the cationic and neutral ones are limited to water adsorption.

Bicyclic peptides exhibit improved metabolic stabilities, membrane permeabilities, and target specificities over their linear and mono-cyclic counterparts, however, efficient bicyclization remains challenging. Here, the authors develop a one-pot tandem chemoenzymatic bicyclization by combination of penicillin-binding protein-type thioesterase-mediated head-to-tail macrolactamization and copper(I)-catalyzed azide–alkyne cycloaddition.

Oxide-derived copper materials display high catalytic activities for the electrochemical reduction of carbon dioxide, but the mechanisms surrounding this high performance are not fully understood. Here, the authors use time-resolved operando spectroscopy to probe the structural dynamics of copper oxide reduction and reformation, both in the bulk and on the surface of copper foam catalysts.

Norcoclaurine synthase from Thalictrum flavum (TfNCS) has been demonstrated to display high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, however, the mechanism and factors related to this high stereospecificity remain unclear. Here, the authors conduct quantum chemical calculations and reveal the rate-limiting step and differential energy barriers for the reactions of two enantiomers of α-methylphenylacetaldehyde, as well as key residues related to stereospecificity.

Polyethylene terephthalate (PET) can be depolymerized by the Ideonella sakaiensis PETase enzyme, however, questions remain about the precise catalytic mechanism. Here, the authors use unbiased QM/MM MD simulations to determine optimal mechanistic descriptions of the acylation and deacylation reactions, revealing the rate-limiting step and key interactions within the catalytic triad and Trp185 conformation.

The detection of cancer in its early stages can greatly prevent disease development, however, current technologies for tumor detection present several limitations. Here, the authors develop a paper-based electrochemical device for detecting cancer-derived small extracellular vesicles (S-EVs) in fluids, recognizing αvβ6-containing S-EVs down to a limit of 0.7*10³ S-EVs/mL with a linear range up to 10⁵ S-EVs/mL.

Organocatalytic ring-opening polymerization (ROP) is a versatile method for synthesizing well-defined polymers, however, precision synthesis of polysiloxanes remains challenging due to a mismatch in polarity between initiators, monomers, and polymers and the formation of scrambling products. Here, the authors describe a binary organocatalytic ROP of hexamethylcyclotrisiloxane employing organic bases as catalysts and (thio)urea as cocatalysts, achieving solubilization of multifunctional silanol initiators and 90% monomer conversion.

Body odor (BO) changes during human development, however, the molecular basis for this has not been fully elucidated. Here, the authors investigate the odorant composition of BO samples in infants and post-pubertal children, revealing qualitative and quantitative differences in the composition of the samples.

There are numerous examples of plasmonic photothermal catalytic reactions, but the participation of hot carriers remains a subject of vigorous debate. Here, the authors construct a plasmonic nanohybrid system that is unstable above 580  K to show that hot electrons are the main culprit in the photoelectrocatalytic reduction of CO₂ to CO.

Lignin-derived phenolic acids can be upgraded to styrene derivatives through chemoenzymatic processes, however, the scale-up of such processes remains challenging. Here, the authors find that controlling the water activity during the decarboxylation of bio-based phenolic acids, including through the integration of a water reservoir, enables high conversions and efficient reaction times, that can be combined with a versatile acyl donor substrate scope.

Carbocations are highly electrophilic intermediates involved in S_N1 reactions, such as the direct alkylation of low-reactivity nucleophiles, however, in situ activation of leaving groups in such reactions remains challenging due to the unstable nature of the carbocations, leading to cross-reactivity between nucleophiles and leaving group activators. Here, the authors develop a two-step procedure to avoid such cross-reactivity: they generate carbocationoids as coordinatively stabilized carbocations in one nucleophile-free solution, and then complete the alkylation in another reaction vessel under mild conditions.

Retention time prediction in liquid chromatography plays an important role in molecule annotation and method optimization, however, the accuracy of current quantitative structure−retention relationship models highly depends on the chromatographic method (CM). Here, the authors develop a generic model featuring a post-projection calibration to eliminate the impact of specific CMs, reaching similar ranking levels of putative candidates among different CMs.

Computer-aided retrosynthetic planning algorithms such as Monte Carlo Tree Search (MCTS) and A* search can expedite the identification of synthetic pathways, however, achieving a high success rate remains challenging. Here, the authors develop an enhanced search algorithm by incorporating the exploration capability of MCTS into A* search, achieving synthesis success rates of up to 100%.

The effective control of chirality on surfaces is crucial for applications such as enantioselective heterogeneous catalysis and nonlinear optics. Here, the authors study the on-surface synthesis of organometallic polymers and their chiral expression on Ag(110), demonstrating that kinetic effects play an important role in determining polymer chirality.

CO₂ electrolyzers with gas diffusion electrodes take advantage of improved mass transport of gaseous CO₂ to the catalyst surface to afford increased current densities, but the complex and coupled multi-phase processes occurring inside the electrolysis device are not fully understood. Here, the authors use a two-dimensional volume-averaged model of the cathode side of a microfluidic CO₂ to CO electrolysis device with a gas diffusion electrode and find that under high cathodic potential, the catalyst layer is prone to forming H₂ and CO bubbles, mirroring observed experimental electrode instability.

Fluorescence-based oligonucleotide probes, also known as molecular beacons (MBs), are popular for detecting nucleic acids with high specificity. Here, the authors demonstrate self-sequestration of MB-based biosensors and target strands within peptide-based coacervates, increasing local concentrations and significantly increasing the sensitivity and kinetics of the DNA biosensors.

Ipatasertib is a potent Akt (protein kinase B) inhibitor synthesized via a chemoenzymatic process. Here, the authors use mutational scanning and algorithm-aided enzyme engineering to optimize a ketoreductase from Sporidiobolus salmonicolor and generate a 10-amino acid substituted variant exhibiting a 64-fold higher k_cat and improved yield for the relevant alcohol intermediate, with ≥ 98% conversion and a diastereomeric excess of 99.7% (R,R-trans) from 100 g L⁻¹ ketone after 30 h.