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Efficient grand canonical global optimization with on-the-fly-trained machine-learning interatomic potentials
The characterization of nanostructured materials under reactive environments is challenging due to the complexity of the structural motifs involved and their chemical transformations. Global optimization approaches allow predicting stable structures for targeted materials, but addressing the configurational and compositional search spaces is both computationally demanding and inefficient, especially when first-principles calculations are required. In this work, we implement and evaluate a computationally efficient grand canonical global optimization algorithm able to identify stable structures and chemical states of targeted systems under given reaction conditions (e.g., reactant pressure and temperature). The algorithm leverages an on-the-fly trained machine-learning interatomic potential based on sparse Gaussian process regression and the smooth overlap of atomic positions descriptor to reduce the number of first-principles energy evaluations carried out during global optimization searches. The ab initio thermodynamics framework is incorporated to approximate the Gibbs energy of evaluated candidates, performing environment-aware optimizations over multiple stoichiometries. We demonstrate the computational performance of this approach and its ability to reproduce some literature examples.
Ion Transfer During Ionomer Contact Electrification: Binding Affinity Controls Charging
ABSTRACT Contact electrification occurs ubiquitously in nature, but the identity of charge carriers in most situations remains uncertain, with electrons, ions, or nanoscopic material fragments as viable candidates. One material where the species transferred seems more certain is ionomers, i.e., polymers that contain mobile ions balanced by fixed counter‐charges. When ionomers touch a neutral surface, the latter becomes charged in the sign of the mobile ion, strongly suggesting ion transfer. However, the mechanism and governing factors of transfer remain poorly understood. Here, we demonstrate that binding affinity between mobile ion and ionomer controls charge transfer with ionomers. We use ionomers with fixed anions and cations and perform ion exchange to create samples with a series of transferrable ions. We observe a strong binding‐affinity dependence for the anionic ionomer, such that mobile cations with the highest affinity transfers the least charge. Weaker, yet clear dependence was measured for the cationic ionomer, which follows the hydration free energy of the mobile anion. Using inductively coupled plasma optical emission spectroscopy (ICP‐OES), we confirm transfer of the mobile ions to the counter sample's surface. Our results confirm the identify and mechanism of charge transfer with ionomeric materials, with potential implications for contact electrification more broadly.
Three-slab model for the dielectric permittivity of a lipid bilayer
A model for the tensorial dielectric permittivity of phospholipid membranes is presented here. The four-nanometer-thick membrane is treated as a composite made up of three dielectric slabs: one for each of the two phospholipid head-group regions and one for the entire domain spanned by the lipid tails. Equal and opposite bound surface charge densities surround each head-group slab and account for the membrane dipole potential. Three-slab model parameters are obtained from molecular dynamics simulations and capture both the zero-field electric potential and the membrane response to applied electric fields. The tail region is well-approximated as having vacuum permittivity, while the head-group region is highly anisotropic due to the configurations of molecular dipoles. For the bilayers studied, the out-of-plane permittivity of the head-group region is 10–15 times that of the vacuum, while the in-plane permittivity is an order of magnitude larger. Membrane responses to applied electric fields up to 30 millivolts per nanometer are found to be in the linear regime. The model overcomes a fundamental limitation of microscopic theories—where the out-of-plane permittivity lacks a meaningful continuum interpretation in the head-group region due to large gradients in the local electric field—by averaging over slab widths, thereby introducing new length scales. Our approach can be extended to characterize interfacial systems with similar microscopic permittivities.
Discovery of an Antiviral Electron Transfer Process to Create Catalytically Self‐Sufficient Viral Restriction Factors
ABSTRACT Engineering immune‐silent, catalytically self‐sufficient antiviral restriction factor enzymes (iCAREs) provides a proof‐of‐concept for developing autonomous enzymes for future antiviral applications. To rationally design these enzymes, we sought to identify and engineer components of the intrinsic immune system. Here, we identified the endoplasmic reticulum (ER)‐anchored cytochrome b5 reductase 3 (CYB5R3) as a putative electron donor to the ER‐anchored and interferon‐stimulated antiviral radical S‐adenosylmethionine (SAM)‐dependent nucleotide dehydratase (SAND), or RSAD2 (viperin) in humans. We demonstrate that their functional partnership depends on co‐localisation. We obtained insights into the structure of the RSAD2:CYB5R3 complex and, using mutagenesis, identified the structural elements required for electron transfer. Based on this discovery, we engineered iCAREs that autonomously generate an antiviral nucleotide analogue to chain‐terminate viral RNA polymerase activity. Because iCAREs are self‐sufficient and do not require recruitment of endogenous redox partners, they are predicted to avoid interference with numerous biological processes associated with single‐domain redox partners such as CYB5R3, including electron delivery to the oncogenic enzyme stearoyl‐CoA desaturase (SCD1). This work solves a long‐standing question of why ER localisation is critical for RSAD2 activity, resolves a key mechanistic question in radical‐SAM enzymology, and establishes a general strategy to engineer self‐sufficient radical‐SAM enzymes for biotechnological applications.
Vibrational carbon character analysis of astronomical PAHs
Emission features of astronomical spectra typically attributed to aromatic and aliphatic portions of polycyclic aromatic hydrocarbons (PAHs) should not be so clearly binned as previously ascribed. Vibrational carbon character analysis (VCCA) herein shows that the 3.4 μm aromatic infrared emission band (AIB), typically labeled as “aliphatic,” possesses more than 45% non-aliphatic (i.e., aromatic) character for the test case of indene, the smallest astronomically detected PAH. Significant non-aliphatic character is seen as well for the 6.85 and 7.25 μm emission bands of indene, which are also considered to be markers of aliphaticity. VCCA predicts similar behavior for all three emission bands in the case of 2-ethynyltoluene, the proposed interstellar precursor of indene. Although the typical aromatic emission bands (i.e., 3.3 and 6.2 μm bands) exhibit slight aliphatic character for both indene and 2-ethynyltoluene, these bands are primarily aromatic. While these are only two example molecules, if significant character mixing occurs for the emission bands of most potential AIB carriers, current aliphatic/aromatic AIB attributions must be reconsidered.
Logic‐Responsive Superspherical Nucleic Acid Enables Tumor‐Specific Multiplexed Gene Silencing for Efficient Cancer Therapy
ABSTRACT Gene‐targeted therapies are of considerable interest for targeting multiple “undruggable” oncogenes. However, their therapeutic efficacy is largely hampered by off‐target toxicity and inherent tumor heterogeneity. Herein, we describe a logic‐responsive s uper s pherical n ucleic a cid (SSNA) with on‐demand, activatable functionality that enables tumor‐specific multiplexed gene silencing for efficient cancer therapy. The SSNA architecture features a nuclease‐resistant spherical nucleic acid core densely coated with a Y‐shaped DNA circuit shell that selectively responds to apurinic/apyrimidinic endonuclease 1 (APE1), a biomarker overexpressed in tumor cytoplasm. Upon intracellular APE1‐triggered shell disassembly, the SSNA enables the controlled release of split antisense oligonucleotides targeting thymidine kinase 1 ( TK1 ) mRNA and DNAzymes that cleave survivin mRNA. Both in vitro and in vivo results demonstrated robust dual‐gene silencing of TK1 and survivin at both transcriptional and translational levels, accompanied by exceptional tumor specificity and minimal off‐target effects. Notably, in a murine MCF‐7 xenograft model, SSNA significantly suppressed tumor growth and extended median survival by an impressive 70% compared to single‐target interventions. By integrating tumor‐specific activation with multiplexed gene silencing, such an SSNA platform offers a powerful and versatile approach for advancing next‐generation precision cancer therapies.
Assessing the influence of <i>d</i> -orbital radius on formation of localized photogenerated states in corundum metal oxides
Photogenerated polarons are fundamental to the photophysics of transition metal oxide semiconductors. It is, therefore, imperative to understand the mechanisms by which polarons form upon photoexcitation of transition metal oxides to realize their potential in photoapplications. Hematite (α-Fe2O3) is known to form photoexcited small polarons, which limit its performance as a photoelectrocatalyst for water oxidation. Here, we report a systematic comparison of the electronic, optical, and vibrational properties of hematite to those of other metal oxides in the corundum crystal family that elucidates the impact of d-orbital radius on carrier–phonon coupling. Three corundum metal oxides - α-Al2O3 (no d-electrons), α-Fe2O3 (3d), and α-Rh2O3 (4d) - are analyzed with a combined approach of resonance Raman spectroscopy, thermal difference optical spectroscopy, and computational modeling of electronic and vibrational states. We find that the Raman spectrum of α-Al2O3 does not change as the Raman excitation is varied across the visible region, as there is no optical absorption. In contrast, both α-Fe2O3 and α-Rh2O3 exhibit strong coupling of phonons to optical transitions at the onset of absorption, which is evidence of excitation into a polaronic state. Closely comparing the optical polaronic properties of α-Fe2O3 and α-Rh2O3, we establish that increased lattice covalency in α-Rh2O3 arising from the increased radial extension of the 4d orbitals influences which phonon modes mediate photogenerated polaron formation.
Dual Thermal Stabilization Toward Highly Safe and Durable All‐Solid‐State Lithium Metal Batteries Based on Sulfide Electrolytes
ABSTRACT The practical deployment of all‐solid‐state lithium (Li) metal batteries (ASSLMBs) based on sulfide electrolytes is constrained by the thermal–electrochemical coupled failure and safety issues under abusive conditions. Here, a dual thermal‐stabilization strategy is identified and rationalized as the optimal choice to tailor above issues. A fluorinated graphene (FG)‐interlayer is introduced to effectively enhance heat dissipation and deflect Li dendrite propagation inside the ASSLMBs, while an oxygen‐vacancy‐rich copper oxide (CuO 1−x ) additive is applied to efficiently capture reactive oxygen species released from charged cathodes and thus mitigate the electrolyte oxidation. As a demonstration model, the as‐modified Li 6 PS 5 Cl (LPSC)‐based full cells achieve stable cycling over 2000 cycles at 1 C with 96% capacity retention, and well retain the room‐temperature capacity even at 90°C. Accelerated rate calorimetry (ARC) tests on pouch cells further demonstrate enhanced thermal stability. This dual‐thermal‐stabilization paradigm can be extended to sulfide/chlorinated oxide bilayer electrolyte systems.
Quantum kernel-based delta (Δ)-learning for correcting a semiempirical method in the prediction of reaction barrier heights
A quantum machine learning based Δ-learning framework is presented for the prediction of reaction barrier heights of organic molecules. Corrections learned by quantum kernel-based models are applied to mitigate the underlying errors of the semiempirical PM7 method, improving its predictive accuracy toward results obtained at the ωB97X-D3/def2-TZVP level of theory. Both fidelity and projected quantum kernels are implemented using seven distinct encoding circuits and passed to three classical regression algorithms, namely, support vector regression, kernel ridge regression, and Gaussian process regression, yielding a total of 840 benchmarked model configurations across circuit widths of up to 9 qubits and circuit depths of up to five layer repetitions. The encoding circuits are additionally characterized in terms of their expressibility and entangling capability. The top-performing models, constructed using the 9-qubit YZ-CX encoding circuit, predict reaction barrier heights with a mean absolute error ranging between 4.95 and 5.03 kcal/mol, underscoring an improvement of ∼54% over the uncorrected PM7 baseline.
Catalytic Sulfur‐Atom Transfer Enabled by a Bis(disulfide) Titanium Complex
ABSTRACT Multi‐electron processes are key steps in the activation and valorization of small molecules. Due to titanium's electropositivity and the limited accessibility of low‐valent precursors, multi‐electron transformations and their application in atom‐transfer reactions involving this element remain comparatively underdeveloped. Herein, we report a novel four‐electron transformation from a Ti(IV) complex which enabled the formation of a rare titanium bis(disulfide) (Ti(S 2 ) 2 ) in a spiropentane motif. The fast and selective formation of this unique sulfur‐rich complex was leveraged for the catalytic synthesis of isothiocyanates from the corresponding isonitriles. Notably, this reaction is highly efficient even at ambient temperatures and tolerates oxygen‐containing functional groups, marking an advance over noble‐metal catalyzed methods. Detailed mechanistic studies including reaction kinetics and quantum chemical calculations provide insights into the sulfur‐atom transfer process and highlight the role of non‐covalent interactions. Overall, these results represent a new approach in the development of multi‐electron processes and atom‐transfer catalysis with group IV metals.
Unveiling chiral electron–photon correlation effects in circularly polarized optical devices
Strong coupling with circularly polarized vacuum fluctuations offers a viable route to manipulate molecular chirality. While experiments are advancing toward the realization of chiral cavities, a mean-field theoretical framework for describing electron–photon interaction in this platform has been missing. Here, we present a mean-field theory that can be systematically improved to capture the chiral correlation effects responsible for the enantioselective power of chiral light. We use strong coupling Møller–Plesset perturbation theory for accessing the excitation manifold of electrons and chiral virtual photons. We apply the developed methods to selected chiral systems and show that the mean-field theory captures cavity frequency dispersion but fails to describe the chiral discrimination arising from coupled electron–photon excitations.
Remapping the Synthetic Landscape of α‐Tertiary Alkylamines via Dual‐Functional Catechol
ABSTRACT α‐Tertiary alkylamines are privileged motifs with a strong propensity to be bioactive, rendering their efficient synthesis fundamentally important across diverse areas of chemistry. Despite recent advances in aliphatic amine preparation, the direct construction of hindered α ‐tertiary amines remains a long‐standing challenge. Here, we report a three‐component assembly that exploits the dual role of catechol to enable the modular synthesis of these motifs from readily available, bench‐stable reactants. This method exhibits exceptional functional‐group tolerance and provides access to a variety of synthetically demanding molecular architectures, including consecutive quaternary centers as well as vicinal aminoether and diamine fragments. This approach, therefore, represents a valuable supplement to the chemist's toolbox for α ‐tertiary alkylamines, offering streamlined routes to complex targets and significant possibilities in drug discovery.
Mixed quantum–classical simulations of intramolecular singlet fission
Intramolecular singlet fission is a multistate nonadiabatic process in which vibronic couplings govern ultrafast triplet-pair formation and subsequent relaxation. We benchmark mixed quantum–classical approaches—Ehrenfest dynamics, linearized semiclassical spin-mapping (spin-LSC), and the map-ping approach to surface hopping (MASH) – against numerically exact multilayer multicon-figuration time-dependent Hartree (ML-MCTDH) calculations for models of phenylene-linked pentacene dimers. While Ehrenfest dynamics exhibits pronounced mean-field artifacts and incorrect long-time populations, spin-LSC improves short-time transfer but suffers from transient negative populations and back-transfer effects. MASH provides the most consistent agreement across timescales and molecular variants and remains free of unphysical populations. We further analyze the role of zero-point motion in the initial vibrational distribution and show that it affects the accuracy of different mapping-based approaches in distinct ways. Our results demonstrate that spin-mapping surface-hopping methods offer a robust route to extend singlet-fission simulations beyond the regime accessible to numerically exact quantum dynamics.
Bioinspired Total Synthesis of Myltayloriones A‐B and Mylnudones A–D
ABSTRACT Herein, we report the first asymmetric synthesis of the dimeric sesquiterpenoid myltayloriones A and B. The synthesis features a stereodivergent Echavarren Au‐catalyzed reaction that enables the synthesis of two subunits from a common dienyne precursor, followed by an endo ‐Diels–Alder heterodimerization. Additional key transformations include a ligand‐controlled Pd‐catalyzed reductive hydrogenolysis for C1 isomerization, and a metal‐catalyzed hydrogen atom transfer (MHAT)‐initiated Baran–Giese cyclization to forge a highly congested penta‐substituted cyclopropane. The selectivity of Pd‐catalyzed hydrogenolysis originates from two different oxidative addition pathways, as further elucidated by density functional theory (DFT) calculations. This synthetic work has enabled further investigation of the potent growth differentiation factor 15 (GDF15) inhibitory and insect antifeedant activity exhibited by myltaylorione A. Furthermore, the developed strategy enabled the concise synthesis of mylnudones A–D and revised the structures of mylnudones A and B.
Electronic strong coupling of gas-phase molecular iodine
Molecular polaritons, hybrid light–matter states formed from the strong coupling of molecular transitions and discrete photonic modes, are a compelling platform for optical control of chemical reactivity. Despite the origins of the field of polaritonics in atomic gases, strong coupling of molecular gases remains underexplored. The pristine, solvent-free gas-phase environment may prove ideal for gaining mechanistic understanding of molecular behavior under strong light–matter coupling. In this work, we achieve electronic strong coupling of the B–X, ν1 = 0 → 32, J = 53 → 52 and B–X, ν1 = 0 → 34, J = 103 → 102 rovibronic transitions of gas-phase iodine (I2) lying near 532.2 nm. We access a range of coupling strengths and detuning conditions with fine control over molecular number density and cavity length stabilization. This effort represents the first demonstration of electronic polaritons in a molecular gas and opens a new platform for polariton photochemistry and photophysics.
Engineering Pt/Ionomer Interface via Strengthening Hydrogen‐Bond Network for High‐Performance Low‐Pt Fuel Cells
ABSTRACT A critical challenge in proton‐exchange membrane fuel cells (PEMFCs) is the severely limited catalyst utilization at conventional Pt/perfluorosulfonic acid (PFSA) ionomer interfaces, primarily due to Pt poisoning and impeded mass transport from strong PFSA adsorption. However, existing strategies to mitigate poisoning often struggle to balance adequate proton conductivity with efficient oxygen permeability. In this study, we report hydroxyl‑functionalized covalent organic framework (COF‑366‑OH) as a multifunctional additive that engineers the Pt/ionomer interface and synergistically enhances active‐site availability, proton accessibility, and oxygen flux. The periodically aligned hydroxyl groups in COF‑366‑OH establish a strengthened hydrogen‑bond network with sulfonate groups of PFSA ionomers, which mitigates Pt poisoning and homogenizes ionomer distribution. Coupled with its ordered mesopores, this design enables efficient oxygen diffusion. Consequently, COF‑366‑OH‑modified electrode exhibits a 19% increase in dry‐proton accessibility and a 33% reduction in oxygen‑transfer resistance. At an ultralow Pt loading of 0.05 mg Pt cm −2 , the membrane electrode assembly incorporating the COF‑366‑OH‑modified Pt/C cathode achieves peak power densities of 1.67 W cm −2 (H 2 ‑O 2 ) and 0.83 W cm −2 (H 2 ‑air), representing improvements of 57.5% and 31.7% over the conventional Pt/C cathode, respectively. This work demonstrates a hydrogen‑bond‐driven interface engineering strategy that simultaneously addresses Pt poisoning and mass‑transport limitations, providing a promising direction for low‑Pt PEMFCs.
Simple analytical models of spectral focusing stimulated Raman scattering microscopy
Stimulated Raman Scattering (SRS) microscopy is a powerful, rapid label-free, and chemical-specific imaging modality. While the underlying physics is well understood and modeled numerically, we show that, with simple approximations, one can derive equations which enable rapid simulations. Here, we develop an analytical model for spectral focusing SRS microscopy, validate it against numerical simulations, and apply it to the analysis of several experimental implementations. Of use to experimentalists, our model permits rapid simulation of advanced modulation schemes for background (non-Raman) signal removal in SRS microscopy. We compare and discuss their relative advantages and drawbacks.
Porous Organic Cage Liquid Stabilizes Pd Nanoclusters for Ambient H <sub>2</sub> Capture and Alkyne Semihydrogenation
ABSTRACT The design and synthesis of novel supports for stabilizing highly active ultrafine metal nanoparticles (MNPs) is critically important across diverse scientific fields as it enables more efficient utilization of their high density of accessible active sites. However, the potential of emerging porous liquid (PL) materials to protect such MNPs remains largely unexplored. Herein, we report the rational design and synthesis of a new PL based on a porous organic cage (POC), termed CPOC‐PL , constructed via condensation between four concave tetraformylcalix[4]resorcinarene caps and eight long‐chain polyethylene glycol‐functionalized diamino imidazole linkers. This [4+8] CPOC‐PL features a square‐prismatic cavity that serves as an excellent host for encapsulating and stabilizing ultrasmall Pd nanoparticles (∼1.36 nm in diameter) through a coordination‐reduction process. The resulting Pd@CPOC‐PL exhibits notable hydrogen gas uptake under ambient conditions, with ∼2.1 H atoms per Pd atom. Leveraging its fluidic nature and efficient hydrogen capture ability, Pd@CPOC‐PL also demonstrates outstanding catalytic performance in the semihydrogenation of alkynes at ambient conditions. This work presents a generalizable strategy for the rational construction of functional POC‐based porous liquids for practical applications.
A theory of electronic structure for coarse-grained resolutions
We present a stochastic diabatic projection method for constructing electronic structure models that operate at coarse-grained (CG) molecular resolutions. By minimizing the relative entropy of joint electronic-nuclear distributions between the fine-grained (FG) and CG resolutions, we derive a stochastic effective Hamiltonian that decomposes CG configuration dependent electronic structure into deterministic means and residual fluctuations. This framework bridges downfolding and molecular coarse-graining theory, enabling the systematic reproduction of electronic structure renormalized over eliminated nuclear and electronic degrees of freedom.
Design of Isomeric Covalent Organic Frameworks for Realizing Low‐Temperature Sodium Storage
ABSTRACT High‐performance low‐temperature sodium‐ion batteries (SIBs) are essential for energy storage in extreme environments, which, however, is severely hindered by the sluggish reaction kinetics due to the slow ionic diffusion and lattice shrink. Herein, we report an isomeric design strategy for anthraquinone‐based covalent organic frameworks (TPAQ‐COF) to optimize sodium storage by regulating the spatial arrangement of carbonyl groups. By engineering TPAQ‐COF with adjacent carbonyl coordination sites (isomeric TPAQ‐COF, i‐TPAQ‐COF), we successfully leverage a synergistic chelation effect to facilitate sodium ion storage at low temperature. As a result, i‐TPAQ‐COF exhibits a superior reversible capacity of 153 mAh g − 1 at 0.1 A g − 1 and an outstanding long‐term cycling stability (95% retention after 5000 cycles at 2 A g − 1 ) under ambient conditions. More importantly, the i‐TPAQ‐COF demonstrates remarkable low‐temperature resilience, delivering 124 mAh g − 1 at ‐30°C (representing 82% of capacity at room‐temperature) with negligible decay over 200 cycles, and retaining 75% of room‐temperature capacity (114 mAh g − 1 ) even at ‐40°C. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations reveal that the adjacent carbonyl groups in i‐TPAQ‐COF exhibit a synergistic chelation effect, which not only elevates the discharge voltage, facilitates the capture of sodium ions but also effectively promotes ion transport.