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Pharmacophore-directed retrosynthesis targets a potential pharmacophore from early on in a natural product synthesis and incremental increases in the complexity of this minimal structure enable a SAR profile to develop over the course of the campaign. The method is applied to gracilin A, finding simplified derivatives displaying potent immunosuppressive effects or selective neuroprotective effects in cell-based assays.

Zero-field nuclear magnetic resonance can identify species and collective behaviors in mixtures without applied magnetic fields. Here the authors demonstrate its use for resolving proton exchange in ammonium and for the detection of hyperpolarized pyruvic acid, an important imaging biomarker.

The origin of the covalent H–H bond is understood to be driven by kinetic energy lowering. Here the authors show this is not the case for bonds between heavier elements likely due to the presence of core electrons, and that constructive quantum interference instead drives bond formation.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

Genomic comparisons with a new amphioxus chromosome-scale genome assembly reveal details of the early evolution of vertebrate genomes.

The interactions of lignin with polysaccharides in plant secondary cell walls are not well understood. Here the authors employ solid-state NMR measurements to analyse intact stems of maize, Arabidopsis, switchgrass and rice and observe that lignin self-aggregates and forms highly hydrophobic microdomains that make extensive surface contacts to xylan.

A quinone-mediated hydrogen anode design shows that hydrogen can be used as the electron source in non-aqueous reductive electrosynthesis, for a more sustainable way to make molecules at larger scale.

Elaborated catalysts design can substantially enhance performance under unfavourable reaction conditions. Amorphous nickel hydroxide proton sieve used to modify local chemical environment on a platinum surface results in unprecedented performance for alkaline hydrogen evolution reaction.

Calmodulin (CaM) regulates a variety of membrane channels in response to Ca2+, but the precise mechanisms are still unclear. Now a combination of single-particle EM, molecular dynamics simulations and functional assays is used to elucidate the structure of Ca2+–CaM bound to the full-length aquaporin AQP0, revealing a cytoplasmic gate that is closed upon CaM binding to control channel permeability in an allosteric manner.

Photon upconversion methods demonstrated thus far involve challenging requirements. Here Weingartenet al. demonstrate a mechanism called cooperative energy pooling, in which multiple photoexcited sensitizers resonantly and simultaneously transfer their energies to a higher-energy state on a single acceptor.

No experimental evidence exists for intra-helical motion of DNA at the μs timescale, which has been attributed to technical difficulties in observing motion in this time range. Here, the authors demonstrate, using extensive molecular dynamics simulations and experimental analysis, that such motion is effectively absent from a B-DNA duplex.

Exploiting the peculiar properties of graphene, a series of high-performance glass-on-graphene devices, such as polarizers, thermo-optic switches and mid-infrared waveguide-integrated photodetectors and modulators are realized.

The use of colloidal quantum dots in optical applications is hampered by difficulties in optimizing their physical properties. The synthesis of high-quality quantum dots that simultaneously exhibit narrow emission linewidths and minimal blinking potentially overcomes this problem.

Mutations in genes affecting intraflagellar transport account for some but not all cases of short rib polydactyly syndromes. Here Taylor et al. use whole exome sequencing and in vivo cell line assays to identify novel disease associated mutations in DYNC2LI1.

The operational simplicity of modifying the surfaces of thiol-capped gold nanoparticles has been a hallmark of their success in materials chemistry, despite having limited control over the surface composition. Now, S_NAr chemistry on activated perfluoroaromatics has been shown to mimic this simplicity and allow for the synthesis of atomically precise nanomolecules.

Isolation of individual cells from mixed populations is desirable for many biomedical applications. Here the authors use photoswitchable Pdots to allow 'optical painting', where cells of interest are marked based on their visual characteristics, and can then be isolated by fluorescence activated cell sorting.

This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars.

Silicon is a promising anode material for lithium ion batteries, but suffers from structural degradation during operations. Here, the authors combine silicon with a room temperature ionic liquid to stabilize the electrode-electrolyte interface and achieve long-term cyclability.

Here, using animal models, Deodhar et al. single parenteral dose of dolutegravir (DTG) prodrug nanocrystals sustains drug protein-adjusted 90% inhibitory concentration for up to a year, without injection site reactions or systemic toxicities.

Lithium-metal batteries offer much promise for high-energy storage but their operation under extreme temperatures is challenging. Here the authors report a temperature-resilient high-performance lithium-metal battery based on a liquefied gas electrolyte that also has promising properties in safety and recyclability.

Identification of a hyperstable boronate enables automated lego-like synthesis to access a wider range of three-dimensionally complex small organic molecules rich in Csp³–C bonds. 

Engineered variants of cysteine dioxygenase containing a halogen-substituted tyrosine analog provide insights into the process of Cys–Tyr cross-link formation and indicate that the enzyme can catalyze oxidative cleavage of a carbon–fluorine bond.

The F + para-H₂ → HF + H reaction is an important source of HF in interstellar clouds; however, its unusually high rate and its dynamics at low temperature are not fully understood. Now, quantum-state resolved crossed-beam scattering measurements and anion photoelectron spectroscopy have revealed that this reactivity is caused by a resonance-enhanced tunnelling effect involving a post-barrier resonance state.

Despite the progress in C(sp³) cross-coupling reactions, full control over the stereochemistry remains a challenge. Here, the authors show that phosphine-containing axially shielded Pd(II) complexes enable Suzuki-Miyaura cross-couplings of unactivated C(sp³) boronic acids with perfect stereoretention.

Here the authors report a study measuring lifetimes of core-hole states of ICl molecule using attosecond transient absorption spectroscopy. They find that lifetimes depend on the alignment of the orbital relative to the molecular axis.

H₂ roaming is associated with H₃⁺ formation when certain organic molecules are exposed to strong laser fields. Here, the mechanistic details and time-resolved dynamics of H₃⁺ formation from a series of alcohols were obtained and found that the product yield decreases as the carbon chain length increases.

Microfluidic systems controlled by a single driving pressure are programmed to exhibit complex flow-switching schemes and a fluid analogue of Braess’s paradox by exploiting fluid inertia and network design.

Businesses and the public can keep watch when governments fail to provide environmental data, say Angel Hsu and colleagues.

Increasing the edge concentration of metallic MoS₂ nanosheets will improve their electrocatalytic performance for hydrogen evolution. The activity of MoS₂ can now be enhanced by facilitating electron injection from the electrode to the catalyst.

Despite their appearance in a number of bioactive natural products, the synthesis of 5-membered carbocycles has received much less attention than synthesis of their 6-membered counterparts. Here, a Michael-aldol-β-lactonization cascade is used to forge two C-C bonds, one C-O bond, two rings and up to three contiguous stereocentres and deliver complex cyclopentanes with high levels of relative and absolute stereocontrol.

Molecular inhibitors of amyloid formation could help combat Alzheimer's disease, type 2 diabetes, and other major human diseases. Here, two-dimensional infrared spectroscopy and residue-specific isotope labelling are used to obtain detailed structural information on amyloid-inhibitor complexes. The unexpected behaviour observed helps to explain the moderate activity of the inhibitor studied.

The direct transfer of primary amino and hydroxyl groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge. Here, it is demonstrated that bench-stable N–H and N–alkyl oxaziridines can be used as efficient multifunctional reagents, without deprotonation, for the direct primary amination and hydroxylation of (hetero)arylmetals.

The room-temperature magnetism of colloidal doped semiconductor nanocrystals can be manipulated reversibly by controlling their electric charge state, making such materials attractive for potential spintronics applications.

Computational design enables the generation of a chimeric construct of the RAS exchange factor SOS that is specifically activated by a small molecule. The expression of this construct in different cell types reveals distinct phosphorylation kinetics.

Sub-ångström-resolution indentation measurements and semi-analytical methods indicate that, for few-layer-thick films, the elasticity perpendicular to the plane is sensitive to the films’ structure and the presence of intercalated molecules.

Chunyan He and colleagues report genome-wide association studies for both age at menarche and age at natural menopause from the Nurses Health Study and the Women's Genome Health Study.

A simple and much-studied example of vibrationally inelastic collisions is the crashing of a hydrogen atom into a deuterium molecule. This experiment reveals a different inelastic scattering mechanism: it observed vibrational excitation even in collisions where the two species merely graze each other, and which is attributed to extension of the D-D bond through interaction with the passing H atom. This tug of war mechanism should be at play whenever attraction can develop between the colliding partners.

Spin-coherence times of ∼0.9 µs and Rabi oscillations with frequencies between 2 and 20 MHz have been observed in colloidal ZnO quantum dots doped with Mn²⁺.

In this study, the authors examine the effects of caffeine on long-term memory. They find that a specific caffeine dose administered shortly after participants studied images improves image-recognition performance a day later. This suggests that caffeine may enhance memory consolidation separately from other cognition-enhancing effects.

The four-coordinate iron sites of typical iron–sulfur clusters rarely react with small molecules, implicating three-coordinate iron in many catalytic cycles. Now, a [4Fe-3S] cluster featuring three-coordinate iron sulfide that resembles the proposed substrate binding site has been synthesized. This cluster shows biomimetic reactivity with a low-spin electronic configuration.

How interactions between binding partners form or break is hidden in the transition paths from the encounter to the formation of a stable complex. Here authors use single‐molecule spectroscopy to measure the transition path times for the association of two intrinsically disordered proteins that form a folded dimer upon binding and identify a metastable encounter complex.