Asymmetric catalytic hydroamination of alkenes represents one of the most efficient strategies for constructing chiral N-heterocycles. Herein, we realize the asymmetric intramolecular remote hydroamination of internal cis-alkenes via palladium catalysis. The reaction proceeds through sequential alkene aminopalladation, palladium migration, and reduction of terminal alkyl-palladium intermediates. The corresponding nitrogen-containing heterocycles are furnished in good yields with high enantioselectivity, offering a straightforward and robust route to the synthesis of piperidone, pyrrolidone, and oxazolidin-2-one scaffolds. Detailed mechanistic studies disclose that the stereochemical outcome and reversibility of aminopalladation are strongly solvent-dependent. Furthermore, the reduction of the alkyl-Pd(II) bond is highly susceptible to steric hindrance, which enables the achievement of remote asymmetric hydroamination.

Anaerobic carbon monoxide dehydrogenase (CODH) enzymes interconvert CO2 and CO under mild conditions and with near perfect selectivity. The CODH active site, termed the C-cluster, is a [NiFe3S4]-Feu cluster that can reside in several different oxidation states. Despite decades of research, the electronic structure of the C-cluster remains unresolved, and the metal oxidation states are ambiguous. In this study, we interrogate a series of synthetic clusters with [NiFe3S4]3+/2+/1+ cores in multiple oxidation states as models of the C-cluster cubane core. Each cluster is characterized using crystallography, spectroscopy, magnetism, and computations. The most oxidized cluster, [NiFe3S4]3+, is best described as having Ni2+ and three Fe3+ sites. Remarkably, X-ray absorption spectroscopy (XAS) data show that reduction to the [NiFe3S4]2+ state results in reduction of nickel to Ni1+, even though nearby Fe3+ sites are present. The fully oxidized Fe3+3 subsite can be reduced only after nickel has reached the Ni1+ state. These results demonstrate that Ni1+ is a readily accessible oxidation state in FeS clusters that are topologically relevant to the CODH C-cluster.

Flow electrochemical synthesis is a promising platform for constructing value-added targets such as d-labeled compounds. However, its efficiency and broader application are limited by the unproductive or kinetically mismatched counter half-reactions and architectural constraints of conventional flow cell architectures. Here, we report a redox-decoupled strategy within a single-cell tandem flow reactor that separates a classical substitutive deborylation-deuteration into sequential electrochemical steps. This approach enables the universal, metal-free deuteration of diverse organoboron species, including boronic acids, borate esters, and borates, across alkyl, (heterocyclic) aryl, alkenyl, and other derivatives (>100 examples). Using D2O as a cost-effective d-source, the system achieves excellent yields, d-incorporation, tolerance to the labile functional groups, and significantly improved Faradaic efficiency. The platform demonstrates industrial-grade durability with continuous operation for over 1200 h and enables scalable, unprotected synthesis of deuterated drug d-mexiletine. Overall, this strategy significantly expands the design space of flow electrochemistry, paving an exciting path toward green, economic, and efficient electrosynthesis.

Spatiotemporal control over supramolecular assemblies holds promise for precise theranostics, yet conventional designs often require an extensive modification of the backbone by introducing responsive motifs. Herein, with minimal interference of the molecular backbone, we report a chiral engineering strategy to enhance the pH sensitivity of a tripeptide-drug conjugate (PDC). Specifically, homochiral PDC forms supramolecular nanofibers with a low pH dependence, whereas the heterochiral isomer with alternating D/L residues exhibits a highly pH-dependent self-assembly. Importantly, in carbonic anhydrase IX (CAIX)-overexpressing tumor cells, fibrous assemblies of homochiral PDCs occur at the cell surface, while heterochiral PDCs form nanofibers within lysosomes via protonation. This process subsequently promoted lysosomal membrane permeabilization and enhanced CAIX inhibition, which turns into an efficient way of enhancing cellular Fenton reactions to evoke ferroptosis, thereby improving the antitumor efficacy in breast tumors. Overall, this work proposes a chiral engineering approach for enhancing the pH sensitivity of supramolecular assemblies, which establishes an efficient strategy for spatiotemporal control over supramolecular assemblies and offers alternative insights into the biological effects of heterochirality.

The adsorptive separation of propyne/propylene/propane (C3H4/C3H6/C3H8) is a potential alternative to energy-intensive cryogenic distillation, but it remains a formidable challenge. Here, we report the synergistic binding of propylene in a nitro-functionalized metal-organic framework, MFM-190(NO2), which exhibits an exceptional C3H6 uptake of 9.0 mmol g-1 at 298 K and 0.5 bar (conditions relevant to practical separation) with ideal adsorbed solution theory (IAST) selectivities for C3H4/C3H6 and C3H6/C3H8 at 298 K ranging from 3.3 to 4.3 and from 4.0 to 11.5, respectively. Dynamic breakthrough experiments demonstrate efficient separation of a mixture of C3 hydrocarbons, affording polymer-grade C3H6 (purity >99.9%) with a high productivity of 42.9 mol kg-1 and excellent recyclability over four consecutive cycles. In situ neutron powder diffraction, combined with infrared spectroscopy, reveals that open Cu(II) sites and pendant nitro (-NO2) groups within the pore establish jointly a complementary electrostatic environment for preferential adsorption of C3D6 over C3D8. This study highlights the unique role of nitro groups in fine tuning the balance between the adsorption selectivity and capacity of sorbent materials to tackle challenging separations.

Photocatalysis has reshaped synthetic chemistry and materials science by enabling various transformations under mild conditions using light as a traceless reagent. However, most molecular photocatalysts/photosensitizers only operate within a narrow blue-to-green window, which imposes practical limitations, such as shallow light penetration, competing absorption by substrates and additives, and incompatibility with light-sensitive functionalities. Extending the activity of photocatalysis into the deep-red and near-infrared (NIR) regions offers a compelling solution. However, the lower energy of red and NIR photons typically leads to weakly reactive or short-lived excited states, limiting their photocatalytic capability. A general strategy that enables a single molecular chromophore to function across a broad spectral range remains elusive. Herein we report a molecular engineering strategy that renders multiple excitation pathways generating the same reactive excited state within one ruthenium complex. By incorporating extended π-conjugation into a ruthenium polypyridyl framework, the complex can be activated through one-photon excitation in the short-wavelength visible region, weak direct excitation of the lowest metal-to-ligand charge transfer manifold in the deep red, and two-photon absorption under NIR light irradiation up to 850 nm. Spectroscopic and kinetic analyses demonstrate that distinct wavelength-dependent excitation modes populate a common long-lived MLCT excited state, preserving photocatalytic performance across the UV-vis-NIR spectral window. This wavelength-adaptive behavior enables diverse organic transformations and polymerization processes under conditions inaccessible to conventional photocatalysts. More broadly, this work illustrates how rational ligand design can make multiple excitation modes converge on one reactive state, offering a practical route to ruthenium photocatalysts that operate across the visible-to-NIR range.

The use of a first-row transition metal complex and visible light was exploited to promote the photosynthesis of ammonia from nitrite ions. This is achieved in neutral aqueous solution by employing a cobalt polypyridine complex (CoL) within a light-driven catalytic scheme involving [Ru(bpy)3]2+ (where bpy = 2,2'-bipyridine) as the sensitizer and ascorbate as the electron donor. Under visible light irradiation, the resulting photosystem produces NH3 with a quantum yield up to 3% and a selectivity approaching 100%, achieving a maximum turnover number (TON) up to 2150. Transient absorption spectroscopy and density functional theory provided a robust mechanistic picture, showing that binding of the NO2- substrate occurs at the one-electron reduced metal complex, while also ascertaining the energetic feasibility of subsequent elementary reaction steps. All in all, this work uncovers the great potential of first-row transition metal polypyridine complexes toward the synthesis of chemicals of industrial relevance.

While pristine NaCl is chemically inert in N2-rich environments, this study reports the formation of a novel NaCl(N2)2 hybrid salt at pressures above 50 GPa. First-principles simulations and synchrotron X-ray diffraction analysis revealed that NaCl and N2 react to produce an N-filled salt in which N2 molecules break the isotropic NaCl structure into two-dimensional layers. In contrast to the insulating properties of wide-band gap NaCl, NaCl(N2)2 exhibits a narrow electronic band gap of 3.3 eV, becoming an indirect semiconductor. Further compression to 130 GPa induces the polymerization of N atoms into zigzag N chains. These findings demonstrate the emergence of unusual N bonding under extreme conditions, offering a feasible approach for designing layered NaCl frameworks to modulate nitrogen polymerization.

Charged interfaces are ubiquitous; therefore, their molecular-level understanding is crucial. At such interfaces, an electric double layer (EDL) is formed, and the EDL is considered to consist of the compact Stern layer (SL) adjacent to the interface and the diffuse Gouy-Chapman layer (DL) extending into the bulk. Despite this well-established picture, the properties of each layer, particularly their dynamic aspects, remain poorly understood. Here, we employ two-dimensional heterodyne-detected vibrational sum-frequency generation (2D HD-VSFG) spectroscopy to investigate the hydrogen-bond dynamics in the SL and DL at two oppositely charged lipid/water interfaces. By varying the salt concentration of the solution, we are able to examine the structure and dynamics of water in the SL and the DL separately. We find that the major hydrogen-bond dynamics of not only SL but also DL are markedly different: The dynamics of the DL water are ultrafast (∼0.1 ps) at the positively charged DPTAP interface, whereas it is significantly slower (∼1 ps) at the negatively charged DPPG interface. These results demonstrate that the properties of the water in both SL and DL are significantly affected by the nature of the lipid at the water surface, challenging the widely accepted view that water in the DL is merely bulk-like.

The catalytic enantioselective construction of acyclic quaternary stereocenters remains a central challenge in modern organic synthesis, with far-reaching implications for the design and synthesis of complex natural products and functional molecules. In particular, γ-quaternary stereocenters are exceptionally difficult to access catalytically, as few methods enable precise stereochemical control at positions distal to an activating group. Although [3,3]-sigmatropic rearrangements provide a powerful means to reorganize molecular frameworks with high stereochemical fidelity, their strategic integration with asymmetric catalysis remains underdeveloped. Herein, we report a unified catalytic strategy that merges iridium-catalyzed enantioselective allylic alkylation of α,β-unsaturated malononitriles with a stereospecific Cope rearrangement to deliver γ-quaternary nitrile derivatives with exceptional regio- and enantiocontrol (up to 96% ee). Density functional theory calculations demonstrate that the reaction proceeds via reversible α-allylation followed by a low-barrier, stereospecific Cope rearrangement, thereby establishing a stereochemical relay mechanism for remote stereocenter construction. This platform enables modular, scalable access to α-, β-, and γ-quaternary stereocenters from a common intermediate without erosion of enantiomeric enrichment, establishing a unified strategy for the stereocontrolled construction of densely functionalized acyclic frameworks.

Incorporation of fluorine into pharmaceuticals, agrochemicals, and molecular-imaging agents is of growing importance. Multiple synthetic fluorination methods have recently emerged, and metalloenzymes that are potentially capable of C(sp3)-H fluorination have been reported. Nevertheless, direct, regioselective fluorination of aliphatic carbon centers remains an unsolved problem. Here, we show for the iron(II) and 2-oxoglutarate-dependent (Fe/2OG) l-lysine 4-chlorinase, BesD, which might be envisaged to support C(sp3)-H fluorination by the direct cognate of its native chlorination mechanism, that the enzyme can (1) coordinate F- at its Fe(II) cofactor, (2) activate O2 to form a cis-FeIV(O)(F) (fluoroferryl) intermediate, and (3) use the intermediate to abstract hydrogen from its substrate. In what would be the key final step, fluorine (F•) coupling to the substrate radical is unable to compete with the hydroxyl-radical (HO•) "rebound" step characteristic of related hydroxylases. Electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) data establish that fluorine remains bonded to the iron cofactor through steps 1-3 and therefore available for transfer to the substrate radical. QM/MM calculations suggest that the F•-coupling step is associated with an activation barrier considerably higher than that of HO• rebound, consistent with the observed outcome. The findings experimentally verify prior proposals that the impediment to C(sp3)-H fluorination by the canonical mechanism of an Fe/2OG halogenase lies solely in the final radical-coupling step and set the stage for exploration of whether a potentially surmountable geometric barrier or an insurmountable electronic one is primarily responsible.

Radical-mediated construction of all-carbon quaternary centers offers a powerful approach, yet its application to tertiary alkyl halides under mild conditions remains challenging, often due to the need to orchestrate multiple redox events within a single catalytic cycle. Herein, we report a cyclopropenimine-enabled copper-catalyzed radical cyclization that addresses this challenge. A range of 3,3-disubstituted oxindoles bearing a quaternary carbon center at the C3 position, including those incorporating aryl substituents, was obtained in good yields under mild conditions. Mechanistic investigations, including radical trapping, EPR, kinetic isotope effect experiments, cyclic voltammetry, and DFT studies, reveal that productive catalysis arises from a balance between oxidative C-X bond activation and reductive catalyst regeneration. The phenylene-bridged cyclopropenimine scaffold effectively modulates the redox behavior of the copper center, thereby enabling efficient reactions of tertiary alkyl halides, including chlorides. These findings highlight how the structural features of the cyclopropenimine scaffold regulate competing redox processes within a catalytic cycle and provide a foundation for future radical transformations involving challenging alkyl electrophiles.

Condensate material states ranging from liquid droplets to gels have direct functional consequences, but their molecular determinants, especially for gels, are poorly understood. Here we combined optical microscopy, NMR spectroscopy, and molecular dynamics (MD) simulations to test the hypothesis that backbone hydrogen bonding is a determinant for the material states of XYssYX tetrapeptides. IAssAI forms droplets, but AIssIA forms gels; MD simulations show a higher level of hydrogen bonds in AIssIA condensates than in IAssAI condensates. The addition of a low-hydrogen-bonding peptide, AAssAA, converts AIssIA gels into droplets. The same effect is achieved by increasing the number of terminal A added to AIssIA and by methylating the backbone amides of AIssIA to block hydrogen bonding. 1H-1H nuclear Overhauser effect spectroscopy coupled with MD simulations reveals strong, backbone hydrogen bonding-buttressed molecular networks in AIssIA gels. These results demonstrate that, in addition to side chain-side chain interaction strength, backbone hydrogen bonding, by promoting directional growth, is a determinant of condensate material states.

The 1,3-diol unit is an extremely important functional group motif, and significant effort has gone into development of methods to access it with definition of relative and absolute stereochemistry. Conventionally, stereochemical complexity is built up in a stepwise manner alongside functional group interconversion. It is interesting to consider an unconventional approach whereby the diol may be synthesized nonselectively and the stereoisomers "descrambled" by a chiral catalyst in a subsequent step. We report studies toward this goal using a cinchona alkaloid-derived hydrogen atom abstraction catalyst. This catalyst permits selective hydrogen atom abstraction from a given stereoisomer out of, in some cases three or four, depending on diol substitution. The relative rates of abstraction from different stereoisomers determine the ultimate product outcome after hydrogen atom delivery from an achiral thiol. Symmetrical 1,3-diols participate in a kinetic resolution process whereby one enantiomer is converted to the meso diastereomer with extremely high selectivity, a rare example of a kinetic resolution involving conversion of one enantiomer to an achiral diastereomer. Nonsymmetrical 1,3-diols exhibit different outcomes depending on substitution, and their behavior is systematically explored. Notably, sterically differentiated substrates can allow high ee of both syn and anti diastereomers to be achieved from racemic starting material. On the basis of mechanistic studies, a unified rationalization of the behavior of 1,3-diols of various types with our catalyst is presented, and we additionally evaluate the analogous chiral 1,2-diols, uncovering promising outcomes with nonsymmetrical diols.