Articles

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.

African swine fever virus type II DNA topoisomerase (AsfvTop2) is known to change DNA topology by employing a complex catalytic cycle and is involved in the early stages of viral gene replication, however, the structural and regulatory functions of AsfvTop2 remain underexplored. Here, the authors use cryo-EM to demonstrate six conformers of apo-AsfvTop2 as well as the structures of AsfvTop2-DNA-inhibitor complexes, revealing experimental evidence of their substrate binding mechanism that also shed light to other enzymes.

The effects of co-solutes on protein solubility, stability and function have been well studied, however, some of the theories appear inconsistent and no clear theoretical framework has been established. Here, the authors investigate the NMR titrations of protein barnase with Hofmeister ions and osmolytes to distinguish binding effects from solvent perturbation and provide a coherent explanation for solute effects.

Dual-controlled molecular release is of importance in the construction of controlled delivery systems with high anti-interference capabilities, but has been underexplored in the context of guest release from supramolecular entities. Here, the authors report a coordination cage whereby changes in both the coordinative metal cation and the solvent system are needed to induce guest release.

The atomically precise on-surface synthesis of carbon-based nanostructures is of relevance for electronic and optoelectronic devices, but achieving control over such architectures remains challenging. Here, the authors demonstrate the selective stepwise on-surface synthesis of nitrogen-doped porous carbon nanoribbons with well-defined topologies and structures, and predict variable band gaps dependent on ribbon width.