What makes a chemistry-based innovation challenge successful and how can activities for scientific outreach be improved? In this Viewpoint we discuss the Compound Challenge—a global retrosynthesis competition that has resonated within the scientific community. Through examining the feedback of the participants, we gain valuable insight and lessons into what makes an open innovation activity successful and what pitfalls to avoid.

NAD(P)H-dependent reductases have been established as chemoselective biocatalysts for the asymmetric reduction of C=O, C=N, and C=C bonds. Serendipity, screening, and engineering unearthed that the ability to convert distinct electrophiles is shared by numerous enzyme families. This review sheds light on this underexplored facet of NAD(P)H-dependent reductases and highlights the catalytic versatility of these enzymes.

In this minireview, we highlight the design of single metal atom catalysts at the atomic structure level by focusing on the optimization of catalytic active sites, coordination environment, and active site-support interactions, and briefly discuss their biological catalytic mechanisms for biomedical applications.

This Minireview focuses on strategies for C(sp³)−H activation of hydrocarbons, alcohols, ethers, amines and amides over heterogeneous photocatalysts including inorganic semiconductors, organic semiconductors and metal–organic frameworks (MOFs) photocatalysts.

In this paper, we discuss how nanocatalysts specifically regulate anti-tumor immunity through the tumor microenvironment, and the key is to use unique components or redox status in solid tumors to initiate catalytic reactions for selective release of immune regulators at the tumor site. The biological mechanism of nanocatalytic reaction in regulating antitumor immunity was discussed in detail and the prospects were prospected.

Sonogenetics is an evolving field in which ultrasound is used for the molecular control of cellular functions at different levels, thereby opening new avenues in biological and medical research. Here we discuss sonogenetic mediators and review state-of-the-art sonogenetic methods utilizing thermal and mechanical ultrasonic effects as well as mechanochemically reactive macromolecular systems and ultrasound biomolecular imaging.

Using detailed experiments on a single-crystal electrode, we find that the adsorption strength of a series of carboxylate anions to a metal is linearly corelated with their acid dissociation constant (pKa). Density functional theory shows that this correlation is dictated by the difference in their electron affinity—how easily the anion can give up its electron upon adsorption determines its adsorption strength.

A metal-free photoredox three-component coupling of thiols with readily available alkynes and alkenes has been developed. The reaction mechanism was evaluated by combining ESI-HRMS, EPR spectroscopy, isotope labeling and control experiments. The applicability of the reversible radical addition approach for intermolecular reactions and the key role of π–π stacking interactions in stereoselectivity control have been shown by DFT studies.

Covalent organic framework (COF) nanoparticles constructed with highly hydrophobic monomers as linkers were demonstrated to show a superior amphiphilicity for the formation of stable Pickering emulsions. Because of the high surface areas and tunable pore diameters of COFs, Pickering emulsion catalysis with both a high reaction efficiency and a remarkable size selectivity was achieved.

Iodide preferentially occupies the axial sites in mixed iodide–bromide 2D perovskites. This results in a larger, more negative, ²⁰⁷Pb chemical shift anisotropy that can be distinguished in the isotropic–anisotropic ²⁰⁷Pb NMR correlation spectra.

A dual-salt additive-reinforced carbonate electrolyte (LTFAN) is proposed for stabilizing high-voltage LMBs. The in situ generated nitrogenous and fluoride-rich electrode electrolyte interphase with LTFAN vastly accelerates the interfacial reaction dynamics, and dual-salt additive notably strengthens the moisture tolerance. A thermodynamically favorable electric double layer at charged cathode interface is constructed.

During Li⁺ desolvation, the electrochemical binding ability of TSOH regulates Li⁺ plating morphology along the (110) crystal surface toward dendrite-free Li anode. The electron-rich structure brings lower reduction potential energy and inhibits decomposition of Li salts. Even at −60 °C, a ‘smooth and dense’ SEI is formed, significantly reducing interface transmission resistance of Li⁺ ions.

In dinitrogen (N₂) fixation chemistry, bimetallic end-on bridging N₂ complexes M(μ-η¹ : η¹-N₂)M can split N₂ into terminal nitrides and hence attract great attention. We describe detailed bonding analyses of {[Cp*Cr(dmpe)]₂(μ-N₂)}^0/1+/2+ (1–3) using a combined spectroscopic and computational approach. The focus is to shed light on the electronic structure contribution to their inabilities to split N₂.

The rational design and photophysical investigation of donor-acceptor dyads based on spiro[fluorene-9,7’-dibenzo[c,h]acridine]-5’-one uncover the complex interplay among different light-driven pathways, including intramolecular charge transfer, fluorescence, and intersystem crossing. This investigation offers important guidance for designing novel functional materials for triplet sensitizers and fluorescent sensors.

A cobalt-catalyzed enantioselective C(sp³)−H alkenylation of thioamides with alkynoate esters is presented. The reaction provides alkenylated products in high yields and selectivities that are primed for diverse downstream derivatizations.

Metal-free, and high-yielding sulfur-imination using O-(diphenylphosphinyl)hydroxyl amine to access sulfilimine salts and free-NH sulfoximines has been reported. Its generality was evidenced using a broad substrate scope along with late-stage functionalization of complex, biologically relevant substrates including a notorious amatoxin. DPPH was also shown to iminate sulfoxides with high yields under Rh catalysis to afford sulfoximines.

Major changes—the crystallisation of a junction forming DNA decamer with Λ-[Ru(phen)₂phi]²⁺ shows three different sequence-selective binding modes, and displacement of Sr²⁺ from the minor groove to the interhelical space.

Alpha-ketoglutarate-dependent dioxygenases (αKGDs) are promising biocatalysts for selective oxidations, but their practical use is limited by substrate scope and stability. We engineered an αKGD to hydroxylate a non-native substrate with total turnovers exceeding those of reported αKGDs. The engineered αKGD enabled direct synthesis of a hydroxy-indanone to replace the previous five step synthesis en route to the oncology treatment belzutifan.

Via the synergistic union with mechanochemistry, four archetypal photocatalysis reactions have been realized under solvent-free or solvent-minimized conditions. The mechanophotocatalytic versions feature competitive or superior efficiencies to the solution-state reactions, while also showcasing an enhanced tolerance to aerobic conditions.

An aptasensor was developed with supersandwich DNA (SSW-DNA) modified on the outer surface of nanochannels with hydrophobic inner walls realizing the reliable on-site qualitative and laboratory ultra-sensitive quantitative detection of MC–LR. This work highlights the enhanced performance and broader applicability based on the well-designed single set of probes and nanochannels.

Machine learning allows rapid classification and prediction of the surface area (SA) of nanoporous materials through NMR relaxometry measurements of solvent imbibed in the porous network. Here, principal component analysis (PCA) screens “high” and “low” SA materials, and partial least squares (PLS) provides numerical estimates of SA. This non-destructive technique can be used to help develop new materials with optimized porosity.

Labeled single-entity heparan sulfate (HS) mimetics were synthesized to investigate their cellular distribution, involvement with the immune system, and biodistribution. A fluorescently labeled HS mimetic was observed in the brain of mice and was shown to preferentially associate with immune cells from the tumor site rather than from the spleen. The compounds reported represent a new tool box helping to unravel the mechanism of action of HS mimetics.

Programmable DNA motors with tunable properties. The 0 % GC is the fastest motor and can detect and stall in the presence of single oligonucleotides.

Using in situ methods of atomic force microscopy, X-ray photoelectron spectroscopy and optical microscopy, we visualized the processes of Li plating, stripping and replating tuned by the on-site formed SEI at the argyrodite solid-electrolyte/Li anode interface in all-solid-state Li-metal batteries. Our work provides insights into correlations between the interfacial evolution and cell performance, contributing to the improvement of solid-state energy devices.

Size-tunable nanodisc platforms and NMR revealed the structural mechanism for the cooperative self-assembly of both wild-type and oncogenic mutants of native, fully processed KRAS on the membrane. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Higher-order oligomers retain higher numbers of active GTP-bound protomers by reducing GTP hydrolysis and increasing GDP/GTP exchange.

Fub7, a pyridoxal 5’-phosphate (PLP)-dependent enzyme, catalyzes stereoselective and substrate-dependent regioselective Cγ−C bond formations. Now a structural and enzymological study have elucidated the structural and molecular underpinnings of its catalytic specificity and selectivity, paving the way for harnessing its activity in the synthesis of cyclic noncanonical amino acids.

A powdery h-BN with a micron-sized three-dimensional (3D) structure was developed with a facile NaCl-glucose-assisted approach based on reduced reaction temperature. It exhibited superior advantages in improving the electrochemical performance of polyethylene oxide (PEO)-based electrolytes compared with the commercial two-dimensional (2D) h-BN.

Terminal deoxynucleotidyl transferase (TdT) accepts threose nucleic acid (TNA) nucleotide substrates, and catalyzes de novo synthesis of TNA on the 3’ ends of DNA oligonucleotides. The TNA extension protects DNAs from nuclease digestion, and the DNA-TNA chimeras are used directly as staple strands in the self-assembly of DNA origami nanostructures (DONs). The TNA-shielded DONs are more biologically stable under the physiological environment.

The continuous production of pure formic acid solution with high concentration (2 M) for more than 300 h was achieved by using an MEA electrolyzer containing solid state electrolytes equipped with our developed moist heat ventilation collection system. The resultant formic acid could directly serve as the fuel for air-breathing formic acid fuel cells, which closed the carbon cycle loop of the formic acid economy.

Carbon-supported manganese-centered boundary-rich electrocatalysts show high activity for selective H₂O₂ synthesis. The secondary epoxide and hydroxyl groups surrounding Mn−N₃−O sites and the O₂ enrichment in the curved boundaries together contribute to the activity enhancement for the targeted electrosynthesis.

A potassium silole salt reacts with erbium or yttrium cyclo-octatetraenyl half-sandwich complexes via insertion of a silole silicon atom into a carbon-oxygen bond of THF. Analogous reactions involving a potassium germole salt reveal intact transfer of the germole to the rare-earth element, giving germole-ligated coordination polymers. The erbium-containing products are single-molecule magnets, and one example is characterized using high-frequency AC susceptometry.

This work quantitatively disentangles the photoelectronic (PE) and photothermal (PT) effects in plasmon-mediated electrocatalysis using CO₂RR on Ag NPs electrode as the model system. The PE effect prevails over a wide potential window for the CO₂RR to CO, while the PT effect dominates the H₂ evolution reaction at high overpotentials. It is revealed spectroscopically that the carbonyl-containing C1 intermediate applies to the plasmon-promoted CO₂RR to CO process.

Adaptisortion tailored for nonporous polymers has been achieved by dative boron-nitrogen bonding and host-guest binding. The coupling of these two components enables nonporous polymeric crystals to adsorb molecules from solution and undergo recrystallization as thermodynamically favored crystals.

The first completely staggered configuration of a di-superatomic Au₂₅ cluster was solved with atomic precision. The significant torsion angle induces changes in electron coupling and complicates the relaxation pathway of electrons in the excited state when compared with the parallel eclipsed configuration.

The intramolecular ortho photocycloaddition of 2-acetonaphthones has been achieved with high enantioselectivity. The catalytic use of a chiral Lewis acid was critical for the success of the reaction and its mode of action has been elucidated by mechanistic experiments and calculations. The primary photocycloaddition products underwent photochemically or thermally a variety of consecutive reactions.

A series of metalloporphyrin-based boranil covalent organic framework (M-TAPP-COF-BF₂) photocatalysts are fabricated through the post-functionalization strategy. Density functional theory and experimental studies unveiled the synergistic effect of metal (Ni) and BF₂ moiety that alter the electronic band structures and charge carrier mobility, leading to a lower energy barrier for boosting oxygen evolution reaction.

We report the on-surface synthesis of non-benzenoid nanographenes containing different combinations of pentagonal and heptagonal rings. Their structure and electronic properties were investigated via scanning tunneling microscopy and spectroscopy, complemented by computational investigations.

Diastereoselective [4+2] annulation of aldimines with alkenes via benzylic C(sp³)−H activation has been achieved for the first time by the use of half-sandwich rare-earth catalysts with different metals, providing an efficient protocol for the divergent synthesis of both trans and cis diastereoisomers of the multi-substituted 1-aminotetralin derivatives from readily available aldimines and alkenes.

We report that in vivo Cu²⁺ dynamics in the brain can be spatiotemporal visualized using the rational designed BBB-permeable ratiometric photoacoustic probe as the imaging agent. Taking advantages of high-spatiotemporal-resolution imaging abilities of the probe, we have revealed the detailed alternations in Cu²⁺ levels in the Parkinson's disease mouse brain during both the disease progression and drug intervention at micron-resolution.

In order to promote the antitumor efficacy of mRNA vaccines, sweet lipid nanoparticles (STLNPs-Man) are developed by incorporating a mannosylated ionizable lipid to enhance the uptake by DCs through the mannose receptor-mediated endocytosis. Interestingly, STLNPs-Man exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells through the blockade of CD206/CD45 axis to further potentiate the antitumor immunity.

We reported the application of bioorthogonal “Click and Release” (BCR) reaction between prodrug iminosydnone-lonidamine (ImLND) and dibenzocyclooctyne (DBCO) to form highly photothermal-active nanoaggregates with synergistic drug release. The reactants of BCR reaction were grafted on surface of gold nanoparticles (AuNPs) and was proven both in vitro and in vivo to robustly enhance the therapeutic outcome of photothermal therapy.

Despite the existing dye leakage drawback, lipophilic cyanine dyes are still widely used to track liposomes and other lipid systems. In this study, we have revolutionized the lipophilic dye structure by mimicking the entire lipid bilayer, rather than a single lipid molecule. The new conjugated electrolyte-based probes exhibit excellent compatibility with the lipid membrane, coupled with superior and readily adjustable photophysical properties.

The activity of diverse phosphoserine phosphatases was maximized around an intermediate binding affinity of K_m=0.5 mM, supporting the applicability of the Sabatier principle towards enzymes in general. However, there was also a large deviation between theoretical and experimental activity. Therefore, binding energy is an important parameter, but other physicochemical parameters must also be considered to maximize enzymatic activity.

A novel “electrochemical scissor” and “Li zipper”-driven interlayer Li plating protocol in 2D layered transition metal carbides (MXenes) is proposed, where lithium serves as a “zipper” to reunite the adjacent MXene back to MAX-like phase to markedly enhance the bulk phase-structural stability, and a Li halide-rich SEI is formed by “electrochemical scissor” removing the terminals of MXenes to maintain the stability and high Li⁺ diffusivity of SEI.

A synergistic strategy enables the selective synthesis of mono-N-methylated aliphatic primary amines, including deuterium-labelled drugs. This innovative approach combines an earth-abundant manganese catalyst with a weak base, resulting in a practical and sustainable protocol for mono-N-methylation. By effectively inhibiting the formation of formamide byproducts, it eliminates the need for external high-pressure hydrogen.

We develop a novel photo-induced neighbour-deposition strategy to precisely synthesize the heteronuclear dual-atom Ir₁Pd₁-In₂O₃(CP-PD) catalyst. The strong synergistic effect in an angstrom scale endows adjacent diatomic Ir-Pd sites with extraordinary catalytic performance for CO₂ hydrogenation to methanol.

Photo-induced surface reconstruction of Co₃Mo₃N forming amorphous Mo-rich@Co-rich bilayer structure leads to a shortened Co−Mo bond length resulting in improved performance for both photocatalytic hydrogen evolution reaction (PHER) and photocatalytic oxygen evolution reaction (POER) compared to pure Co₃Mo₃N.

Three critical active site residues [L311-S419-C458]/[M311-V419-A458] were identified as the switch of the regioselective C3/C6 reprotonation of germacrene A in sesquiterpene synthase catalysis through the characterization and engineering of two highly paralogous sesquiterpene synthases, AhCS and AhIS, using a combination of isotopic labeling experiments, cryo-electron microscopy, and structure-guided mutagenesis.

Direct room temperature dimerization of carbon monoxide by anionic dicarbenes Li(ADC) has been reported to quantitatively yield (E)-ethene-1,2-bis(olate) bridged mesoionic carbene (iMIC) lithium compounds, CO^en-[(iMIC)Li]₂. They undergo 2e-oxidation to afford 1,2-dione bridged bis iMIC, CO^on-(iMIC)₂ containing compounds while redox neutral salt metatheses yield CO^en-[(iMIC)E]₂ compounds (E=main group species).

Complex natural product functionalizations generally involve the use of highly engineered reagents, catalysts, or enzymes to achieve site-selectivity by lowering a selected transition state energy. We invert this strategy by raising the energy of transition states representing undesirable sites through metal ion chelation, leaving desirable ones accessible to functionalization by a potentially wide variety of electrophilic synthetic methods.

We have created a chromatically complimentary pair of caging chromophores from coumarin-102, by thionation of the exocyclic julolidine oxygen. This enabled wavelength selective photolysis of thio-coumarin-102-GABA on neurons with green versus violet light. When partnered with coumarin-102-Glu, violet and green light could be used for bidirectional neuronal actuation.

Electrochemistry-Informed Neural Network (ECINN) embeds chemistry prior knowledge including the Butler-Volmer, Nernst and Diffusion equations to discover electrode kinetics and mass transport parameter simultaneously from sparse experiments. ECINN seamlessly integrates mass transport and BV equation and provides arguably the best Tafel analysis method. This work encourages embedding domain knowledge to realize strong intelligence with sparse data.

The protection of neighbouring groups during imine condensation reactions modulates the reactivity of building units in the synthesis of 2D covalent organic frameworks (COFs). The reduced reactivity of the protected aldehyde precursor decelerates the kinetics, making the reaction more reversible and improving the crystallinity of 2D COFs.

A Rhodium-catalyzed intramolecular (4+3) annulation of α-arylalkene–benzocyclobutenols has been developed, which proceeds through sequential β-carbon elimination of alcohols, migratory insertion with alkenes, 1,4-Rh shift, and nucleophilic addition to the in situ formed ketones. The protocol offers a diastereo- and enantioselective approach to dihydrofuran-annulated dibenzocycloheptanols with two discontinuous chiral carbon centers built.

The single component flavin-dependent halogenase AetF halogenates a range of 1,1-disubstituted styrenes, often with high stereoselectivity, and AetF and homologues of this enzyme also halogenate terminal alkynes. These findings expand the scope of FDH catalysis, and mutagenesis studies and deuterium kinetic isotope effects provide insight into the unique utility of single component FDHs for biocatalysis.

Efficient CO₂-to-CO dye-sensitized photocatalytic systems are obtained by utilizing noble metal-free photosensitizer (zinc-porphyrin) and catalyst (cobalt-quaterpyridine) derivatives. Upon introducing an additional chromophore (Bodipy), an antenna effect enhanced the photoproduction leading to 42.1 mmol g⁻¹ h⁻¹ of CO and 759 turnover numbers.

Rapid access of diverse polysubstituted 2-oxa-3-azabicyclo[3.1.1]heptanes, which were not readily accessible by known methods, has been realized through Eu(OTf)₃-catalyzed formal dipolar [4π+2σ] cycloaddition of bicyclo[1.1.0]butanes with easily accessible nitrones.

A single-domain ATP “synthase” was derived from bacterial histidine kinases. This enzyme catalyzes ATP synthesis from ADP under mild conditions in vitro by exploiting an AdK-like catalytic mechanism. It can be generally applied as new biomolecular catalyst used for ATP supply to facilitate multifarious vital phosphorylation systems.

A practical copper-catalyzed C4-selective carboxylation of pyridines with CO₂ via pyridylphosphonium salts has been developed. The C−P bond carboxylation with CO₂ was achieved for the first time. This work represents a novel mode of site-selective carboxylation of pyridines, which may be a useful approach in new drug design and discovery in the future.

Planar pentacoordinate hydride has been predicted for the first time in the global minimum C_2V geometry of Li₅H₆⁻ cluster.

Tadpole-like amphiphilic bottlebrush block copolymer (BBC) with UV-responsive self-immolative poly(ethyl glyoxylate) side chains are prepared. Through direct self-assembly such BBC in water, nanoparticles with disc-like morphologies can be prepared. Upon UV irradiation, these nanodiscs demonstrate controlled degradation and disassembly, transitioning from discs to micelles, and facilitating targeted molecular release.

A novel α-diazotrifluoroethyl sulfonium salt was prepared, and it was applied in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time, affording various imidazo[1,5-a] N-heterocycles under mild conditions. This strategy involved a unique trifluoromethyl Rh-carbynoid (CF₃C⁺=Rh), wherein three new chemical bonds were forged at the α-carbon of trifluoromethyl in a single step.

We constructed a nanovesicle vaccine that displays multiple epitope peptides of Echinococcus multilocularis on the surface. The vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit Echinococcus multilocularis infection.

A cascade of three enzymes, E1−E2−E3, is responsible for transferring ubiquitin to target proteins, but the role of the central E2 has been largely overlooked. This work presents a new method, called targeted charging of ubiquitin to E2, or tCUbE, that can follow ubiquitin all the way through its cascade to report on E2 activity and interactions in living mammalian cells.

Two Pd-catalyzed asymmetric [3+2] annulations are disclosed, providing a modular platform for the enantioselective synthesis of chiral thio-oxazolidinones. Preliminary mechanistic studies are performed to rationalize the observed enantio- and diastereo-controls.

To overcome the non-polymerizability of the biaryl-fused monomer DBO, a cyclic ester Me-DBO installed with dimethyl substitution was prepared to enable its polymerizability via enhancing torsional strain while preserving an excellent recyclability. Remarkably, mixing these complementary enantiopure polymers containing axial chirality promoted a transformation from amorphous to crystalline material.

A hydrogen-bonded organic framework (HOF) based on tautomers has been constructed from triarylamidine bromide salts. The HOF exhibits both structural phase transition and proton transfer tautomerism under external stimulation, accompanied by color-switching of the thermally activated delayed fluorescence and room-temperature phosphorescence. The HOF can be used for the highly sensitive and specific detection of acetone.

The CO₂ photoreduction towards CH₃COOH with nearly 100 % selectivity is realized over a catalyst with charge asymmetric metal pair sites, wherein the metal charge asymmetric active sites induced by doping engineering can boost the C−C coupling of double COOH* intermediates.

A series of Cu porphyrins with fine-tuned electronic structures are synthesized and examined as electrocatalysts for hydrogen evolution. Mechanism studies reveal that the catalytically active species switches from a formal Cu^I species to a formal Cu⁰ species upon decreasing the electron density of these Cu porphyrins. This work presents an unparalleled example of regulating hydrogen evolution reaction mechanism via electronic tuning of catalysts.

NaB(CN)₄ exhibits a giant negative thermal expansion behaviour (α_V∼−9.24 ⋅ 10⁻⁵ K⁻¹, 100–200 K; α_V∼−3.7 ⋅ 10⁻⁵ K⁻¹, 200–650 K) with interesting ultralight mass density properties. Non-rigid vibrational modes, characterized by a maximum negative Gruneisen parameter, play a key factor in the generation of the giant NTE observed in NaB(CN)₄.

A convenient three-step synthesis, starting from commercially available pentacenetetraone, gives helical, doubly quaterphenylene wrapped pentacenes. The “Geländer” architecture effectively shields the acene backbones—the para-quaterphenylene derivative displays unique stability with respect to photoxodiation and Diels–Alder reaction with PTAD or fullerene.

Engineered anchor peptide LCI_F16C with a flexible cobalt cofactor Co-L2 hydroxylated polystyrene microparticles using commercially available oxone as oxidant. The oxidation using biohybrid catalyst (Co-L2@LCI_F16C) showed 15 times higher functionalization level than using the free cobalt cofactors.