Despite platinum's well-established catalytic activity for the hydrogen evolution reaction (HER), its limited supply and steep cost hinder large-scale adoption. Earth-abundant bimetallic alloys thus emerge as attractive substitutes, though their vast compositional and structural diversity makes exhaustive density functional theory (DFT) screening unfeasible. Here, we introduce a machine learning (ML)-DFT workflow for the discovery and prioritization of bimetallic HER catalysts. By integrating EquiformerV2 into the AdsorbML surrogate-DFT pipeline, we efficiently predict hydrogen adsorption energies on thousands of alloy surfaces. Sabatier-volcano filtering combined with targeted DFT validation yields a mean absolute error of 0.12 eV across the screened space. Two surface motifs stand out: (i) transition-metal dimers or isolated top sites embedded in Sn- or Sb-rich layers, and (ii) Cu-rich surfaces (Cu-Sn, Cu-Sb) featuring Cu-Cu bridge or hollow sites without direct Sn or Sb interaction. A multiobjective assessment of activity, stability, and cost highlights four synthesis-ready candidatesFeSb, CuSb, CuSn, and NiSbwhich combine platinum-like performance with significantly lower material costs. This integrated ML-DFT strategy transforms an otherwise intractable chemical landscape into a concise, experimental roadmap for earth-abundant HER catalyst development.

The interfaces that govern catalytic reactivity exhibit complex, often coupled, multi-timescale behavior arising from the dynamic organization of ions, solvent molecules, and adsorbates. This complexity is especially pronounced in electrochemical systems where classical models describing the or layers are, in practice, neither static nor ideally defined backgrounds, but active, dynamic contributors to catalytic function. Nevertheless, most electrochemical and spectroscopic probes rely on assumptions of linearity or time invariance, (implicitly) limiting their ability to resolve such intricacies. In this Perspective, we formalize and expand on Dynamic Response Spectroscopy (DRS), a framework that leverages temporally structured perturbations and time-resolved spectroscopic detection to disentangle overlapping, and potentially coupled, nonlinear interfacial dynamics, including non-Faradaic processes and other dynamics not directly reflected in product turnover. While we focus on electrochemical systems as our primary example, the DRS framework is in principle applicable to all (catalytic) systems exhibiting complex interfacial dynamics. We introduce a generalized simulation approach to model spectrotemporal responses to modulation, enabling systematic evaluation of component (elementary reaction and process) retrievability across varying coupling topologies and kinetic regimes. We illustrate the capabilities of DRS using both synthetic systems and, as a case study, experimental operando ATR-SEIRAS measurements during CO electroreduction on copper. The results demonstrate how DRS can uncover solvent dynamics, charging delays, and memory effects that elude current-only, single frequency, or modality analyses. Rather than imposing predefined mechanistic assumptions, DRS allows the system's natural dynamical structure to emerge. We discuss the conceptual implications and practical considerations for implementing DRS across catalytic systems. By acknowledging time-domain complexity, DRS offers an alternative axis of mechanistic insight into the emergent behaviors that govern catalytic activity, selectivity, and stability.

The ability to carry out C-H activation at any site on any heteroaromatic scaffold is a holy grail, offering the potential to revolutionize molecule making. Precision editing, activating, and replacing a C-H bond with a carbon halogen bond opens the way to almost any diversification imaginable. Here, through genome mining and analysis, we present a previously undescribed halogenase tool for precision C-H activation and halogenation. While many halogenated metabolites have been found in the marine environment, indicating the operation of a vast array of halogenases, the presence of such halogenases in other salty environments is less well-known. Here, we describe the first discovery and utilization of a halogenase from a microbe associated with salty and fermented food: specifically brined cheese. Most halogenases explored so far have been identified through their association with a biosynthetic gene cluster of a known natural product. Based on their role in the biosynthesis of that natural product, their native substrate is predicted. Many exciting and unexplored halogenases exist discretely of identified biosynthetic clusters. We describe an approach of carrying out halogenase discovery (unrelated to and unguided by known biosynthetic pathways and their encoded natural products) and predicting non-native substrates that the enzyme can and cannot process as well as the regiochemistry of each biotransformation. Following carrying out discovery , we demonstrate the validation of the discovery results in the laboratory. CHEESY1 (Chemistry Helper Enzyme Enabling SelectivitY1) is shown to regioselectively halogenate a broad structural range of medicinally relevant heterocycles, including quinolines, isoquinoline, phenylpyrazole, and flavonoids. Being able to predict from gene to substrate to product for this powerful class of enzymes, which together afford the opportunity for providing a general solution for precision molecule editing, ahead of carrying out wet experimentation opens up exciting opportunities for the future of chemical catalysis and synthesis.

H is an ideal energy vector, but catalysts for its clean production from water are inefficient or expensive. [FeFe]-hydrogenases are the most active H-converting catalysts in nature, using a unique organometallic active site finely tuned by the protein matrix. M3 type [FeFe]-hydrogenases from and are exceptionally active for H production, and less O sensitive than most other types of [FeFe]-hydrogenases, making them attractive targets for biotechnology. However, they are more challenging to work with because of their large size and the number of iron-sulfur clusters. Here, the [FeFe]-hydrogenase from was systematically engineered to truncate each iron-sulfur-containing region of the F-domain, yielding smaller and easier-to-produce catalytic systems. Detailed characterization revealed that these variants retain high electrocatalytic performance and other essential properties of the natural enzyme.

The conversion of CO into value-added chemicals, such as methanol, offers a promising pathway toward a renewable energy future. However, a precise kinetic control and a highly selective catalyst are necessary to overcome the thermodynamic preference for CO hydrogenation to methane. Rhenium-based catalysts, particularly Re/TiO, demonstrate high activity and selectivity for methanol under high-pressure conditions. For example, at 100 bar and 200 °C, a methanol selectivity of 97-99% was obtained. Catalysts with 1 wt % Re and 5 wt % Re/TiO were used to study the effect of cluster sizes. At 250 °C, the 1 wt % catalyst achieves 97% selectivity at 23% conversion, whereas 5 wt % Re/TiO achieves 74% selectivity at 40% conversion, corresponding to a drop in space-time yield from 65 to 16 g·g ·h, respectively. X-ray absorption spectroscopy provided insights into the structure of the active sites, while density functional theory calculations revealed the effects of cluster size on the energy barriers for H activation, CHOH dissociation, and CHOH desorption, all of which directly influence conversion and selectivity. These results underscore the importance of balancing cluster size for optimal catalyst performance and provide insights into the design of efficient and selective catalysts for renewable methanol production.

This manuscript reports on a Ni/Fe-based bilayer catalyst developed to boost the oxygen evolution reaction in anion exchange membrane water electrolyzers. The electrochemical behavior toward the oxygen evolution reaction of several NiFe/NiFeO metal-oxide bilayer catalysts, prepared by magnetron sputtering at oblique angle deposition (MS-OAD) on a flat stainless-steel substrate, was assessed in a three-electrode electrochemical cell in comparison with the behavior of both a metal NiFe and an oxide NiFeOx single-layer catalyst. The morphology and chemical nature of these catalysts, as prepared and after electrochemical usage, were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. A thorough electrochemical characterization of the different catalyst formulations revealed a higher efficiency for the bilayer catalysts, in terms of both activity and long-term stability, and provided some clues to account for this superior performance in terms of morphology and surface reactivity of each catalyst. As a proof of concept, the best-performing bilayer configuration was then deposited onto a stainless steel felt porous transport layer (PTL) substrate and tested as an ionomer-free anode electrode in a membrane electrode assembly (MEA). Results revealed that the MS-OAD catalysts performed well when deposited on PTLs and that, under this configuration, a bilayer catalyst anode is slightly more efficient than the NiFe single-layer catalyst. Additionally, the possibility of scaling up the MS-OAD procedure to large areas has been demonstrated by the preparation of the bilayer catalysts on a 64 cm PTL and its successful integration and operation in a large prototype single cell.

The synthesis of active pharmaceutical ingredients (APIs) containing heteroaromatic motifs often relies on palladium-catalyzed Suzuki-Miyaura coupling (Pd-SMC), a transformation that can account for a significant portion of the production costs for small-molecule drugs. Nickel-catalyzed SMC offers a more compelling alternative; however, its large-scale implementation has been hindered by high catalyst loadings and a limited scope of heterocyclic coupling partners. Another unmet need in process synthesis is the adoption of polar solvents, such as alcohols and water, to reduce waste generation, improve safety, and improve compatibility with hydrophilic molecules. Here, we introduce a (-ProPhos)Ni catalyst that enables efficient and robust Ni-SMC of heterocycles in -PrOH and water. The -ProPhos ligand features a phosphine moiety tethered to three hydroxyl groups, which can substitute the halide in the oxidative addition intermediate to form a nickel-alkoxy species. This pathway not only facilitates transmetalation but also enhances catalyst stability. Moreover, the hydrophilic nature of the ligand allows Ni-SMC to be performed in pure water. The (-ProPhos)Ni catalyst accommodates a wide range of heteroaromatic core structures, including those present in APIs, with catalyst loadings as low as 0.03-0.1 mol %. The method has been validated on decagram scale and represents a versatile platform with significant potential for adoption in commercial process synthesis.

Metal oxide corrosion severely limits anodic electrocatalysis, particularly at high potentials in acidic environments, where degradation pathways remain poorly defined. This study establishes explicit connections between corrosion and electrocatalysis on tin oxide during water oxidation by examining the roles of lattice defects, reactive oxygen species, interfacial pH variations, and speciation of corroded tin in acid. We first demonstrate the presence of structural defects such as oxygen vacancies and substoichiometric Sn-(II) species by integrating electron paramagnetic resonance spectroscopy, ultraviolet photoelectron spectroscopy, and Mott-Schottky analysis. Kohn-Sham density functional theory calculations reveal that explicit water structures thermodynamically stabilize reaction intermediates and lower reaction overpotentials. Moreover, we propose that water dissociation leads to hydrogen-bonding networks formed by H* and OH* intermediates, which may span the entire catalyst surface and decrease the interfacial pH to drive corrosion. In contrast, the electrochemical generation of reactive oxygen species is shown to play a minor role in catalyst corrosion during water oxidation using inductively coupled plasma mass spectrometry coupled with selective chemical scavengers. Square-wave voltammetry combined with rotating ring-disk electrodes is used to reveal that under open-circuit conditions, only Sn-(IV) cations chemically dissolve from tin oxide, while both Sn-(IV) and Sn-(II) species electrochemically corrode during water oxidation. Our results unveil a dynamic and complicated interplay between corrosive and catalytic pathways on metal oxide electrocatalysts: a decrease in interfacial pH due to water oxidation exacerbates Sn-(II)/Sn-(IV) corrosion. Subsequently, the electrochemical corrosion of Sn-(II)/Sn-(IV) facilitates product formation from lattice oxygen, while the redeposition of corroded Sn-(II) as Sn-(IV) can enable oxygen exchange with water. By elucidating the roles of defects and interfacial chemistry, this work provides a roadmap for engineering improved electrocatalysts that balance activity and stability, a critical step toward scalable and durable energy technologies.

Natural products continue to inspire therapeutic innovation due to their structural complexity and biological potency. Pyrrolobenzodiazepines (PBDs), known for antitumor activity, function by covalently binding to guanine bases in DNA, a mechanism that is inherently species-agnostic. However, their potential as antibiotics remains underexplored, as modest antibiotic activity is commonly seen with this class of compounds. Here, we produce analogs of tilimycin and tilivalline, two PBDs produced by the gut microbe . We mutated NpsA, the nonribosomal peptide synthetase (NRPS) pathway protein responsible for initiating biosynthesis through adenylation of 3-hydroxyanthranilic acid on the pathway to form tilimycin and tilivalline, to enhance promiscuity with substrate analogs. Using structure and informatic-guided mutagenesis, we developed a rapid screening method to identify compatible enzyme-building block combinations to generate a panel of tilimycin and tilivalline analogs. We identified compounds that possess the ability to inhibit DNA polymerase and that show growth inhibitor activity with a DNA-repair mutant of . This work demonstrates the feasibility of NRPS reprogramming to use biocatalytic approaches to access non-natural derivatives with antibiotic potential and highlights tilimycin analogs as candidates for gram-negative antibacterial development.

Photocatalytic water oxidation is a critical half-reaction to realize overall water splitting, yet it remains challenging due to sluggish reaction kinetics and the need for efficient active centers. To overcome these limitations, we introduce a dual strategy combining boron doping with nanocrystal fragmentation to boost the photocatalytic oxygen evolution reaction (OER) performance of ionic carbon nitrides. The optimal catalyst (-KPHI) achieves an apparent quantum efficiency of 4.6% at 420 nm with CoO as a cocatalyst for OER, outperforming most previously reported carbon nitride photocatalysts. Extensive experimental analyses revealed that boron incorporation induces the fragmentation of nanocrystalline domains within the potassium poly-(heptazine imide) (KPHI) matrix, resulting in extended visible-light absorption, improved hydrophilicity, more efficient charge separation, and accelerated water oxidation kinetics. Comprehensive density functional theory calculations further showed that boron preferentially localizes at the edges of heptazine units near structural defects, where it serves as a potential adsorption site for water and substantially lowers the energy barrier for the formation of the *O intermediate.

Ceria has recently regained attention in catalysis research, thanks to its ability to reversibly form and redisperse supported, catalytically active Pt clusters through control of its surface morphology and oxidation state. In the present article, we systematically and independently tune these parameters during CeO(111) film synthesis to investigate their influence on the dimensionality (2D vs 3D) and sintering behavior of size-selected Pt clusters. We present recipes for atomically flat CeO(111) islands and closed films with a thickness of up to 18 monolayers, grown on Rh(111), and characterize them by means of scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and low-energy electron diffraction (LEED). Remarkably, XRD and LEED reveal an epitaxially grown, crystalline, and relaxed closed film of a single domain, with cube-on-cube alignment. Bulk or exclusive surface reduction is achieved by ultra-high vacuum annealing or room temperature CHOH dosing and annealing cycles, respectively. The methanol procedure forms oxygen vacancies only in the surface without reducing the deeper layers of the film or introducing roughening. From STM images, we extract detailed height distributions and coverages of Pt clusters and find that Ostwald ripening already sets in around 600 K on both, fully oxidized and surface-reduced ceria, without any indication for cluster diffusion and coalescence. XPS shows that atom detachment during sintering leads to the intermediate formation of Pt species on oxidized ceria, in line with the redispersed single atoms at step edges observed in the literature. Strikingly, while the clusters appear similarly upon deposition on both supports, they show a distinct temperature-dependent dimensionality upon annealing: Exclusively 3D clusters form on the oxidized support, while most clusters on the reduced support adopt a flat, 2D geometry upon sintering, stabilized by O vacancies.

The copolymerization of CO and epoxides to access polycarbonates represents a promising strategy for CO utilization and for the production of useful polymers. Aiming to explore alternative transition-metal-free approaches that support this chemistry, we have investigated a series of triaryl-catecholatostiboranes as pnictogen-bonding platforms for the copolymerization of CO and cyclohexene oxide (CHO). Our survey of these antimony species has identified motifs that promote this polymerization reaction efficiently, provided that bis-(triphenylphosphine)-iminium chloride is administered as an activator. By coupling these polymerization studies with a careful assessment of the structure, electronic attributes and Lewis acidity of the catecholatostiboranes, this work shows that high activity is generally observed with the weakest pnictogen-bond donors or Lewis acids investigated. Mechanistic studies, which indicate that the polymerization reaction is first order in stiborane, reveal a nonlinear dependence on the CO pressure. This nonlinear dependence could be satisfactorily modeled based on a pre-equilibrium process involving the reversible insertion of the gaseous monomer into the growing chain. Altogether these findings greatly expand the reach of pnictogen bond catalysis while also providing an entry for the use of heavy group 15 elements as competent platforms for CO utilization.

Energy conversion and storage technologies require optimal electrode-electrolyte interfaces to drive electrocatalytic reactions. However, the impact of interfacial phenomena on the catalytic activity remains debated. This study investigates the role of alkali metal cations in interfacial properties and correlates them with electrocatalytic activities toward several energy-related reactions in alkaline media using model Pt(111) single crystal electrodes. Through electrochemical impedance spectroscopy and laser-induced current transient techniques, interfacial parameters, such as the double layer capacitance, the potential of the capacitance minimum, and the potential of maximum entropy (pme), are determined. The latter exhibit a linear dependence on cation hydration energies. Notably, two distinct pmes are observed at the Pt(111)-alkaline electrolyte interfaces, attributed to water dipole reorientation. Correlating pme with reaction activities reveals that interfacial entropy is a robust and general descriptor of electrocatalytic reaction kinetics. Particularly, electrocatalytic activity improves as the pme aligns more closely with the thermodynamic equilibrium potential of the respective reaction, providing a solid framework for optimizing interfacial microenvironments to enhance electrocatalytic performance.

The aluminum-alkyl borate (AAB) salt {[Bu(DMA)-Al](μ-H)}[B-(CF)] (; DMA = -dimethylaniline) is able of fully activating dichloride precatalysts for olefin polymerization and serving as an impurity scavenger, thus deserving to be called a of the well-established methylaluminoxane (MAO). With respect to MAO, it offers the advantage of having a well-defined molecular structure, which was exploited herein to investigate its mechanism of action as a cocatalyst. Particularly, the reaction of the precatalyst (MeSiCp)-ZrCl with and with stable [AlBu(L)], modeling the putative abstracting species [AlBu(DMA)], was studied. The latter reaction led to the isolation of a rare, singly bridged Zr-(μ-Cl)-Al heterodinuclear adduct (), which is a plausible intermediate of chloride abstraction from the precatalyst. Addition of di--butylaluminum hydride (DIBAL-H) to yielded a mixture of several multinuclear Zr/Al adducts with bridging μ-Cl and μ-H fragments (), which were fully characterized by in-depth 2D NMR spectroscopy. Analogous products were observed in the reaction between (MeSiCp)-ZrCl and , reinforcing the hypothesis that they are intermediates of chloride/hydride exchange, which generates a polymerization-active Zr-H species. The solid-state structure of [(MeSiCp)-Zr](μ-H)-(μ-Cl)-(μ -BuAlH) () was determined by single-crystal X-ray diffraction. The presence of the μ-H fragment in appears to be relevant also for determining the excellent impurity scavenging properties of this cocatalyst, as it was found to react more rapidly than Al-Bu moieties upon exposure of solutions of this cocatalyst to atmospheric oxygen and moisture.

We investigated the structure and reactivity of cubic CuO nanoparticles (nanocubes) in the ethanol dehydrogenation (EDH) reaction, which is considered as an ecofriendly process for production of "green" hydrogen and valuable chemicals such as acetaldehyde. High-loaded catalysts prepared by physical mixing of nc-CuO and SiO demonstrated activity considerably higher than that of those prepared by conventional impregnation/calcination. Reactivity tests revealed the catalytic performance (conversion and selectivity) to be independent of the initial state of the catalyst, i.e., oxidized or reduced, due to the facile reduction of the Cu-(I) oxide to metallic Cu in the ethanol atmosphere, as observed by operando XRD, DRIFTS, and near ambient pressure (NAP) XPS. The reduction of nc-CuO is accompanied by strong morphological changes, i.e., the transformation of the nanocubes into roundish nanoparticles and their sintering as shown by TEM and SEM. The Cu-(I) oxide catalyst is initially active in EDH, but the Cu(0) phase formed in situ is considerably more active, and the Cu(0) phase is the only one that exists at the steady state. Analysis of the Cu surface by NAP XPS and CO DRIFTS revealed only the metallic state, with no indication for surface Cu oxide formation under the reaction conditions. The catalysts are stable at relatively low temperatures (∼170 °C) but deactivate, most notably at temperatures above 230 °C, due to coke (mostly amorphous carbon) formation. The results suggest that nc-CuO can be used as a well-defined precursor for the synthesis of high-loaded Cu catalysts for alcohol dehydrogenation at moderate temperatures.

Selective protection and deprotection of hydroxyl groups is pivotal in multistep organic synthesis to circumvent undesired side reactions. Alkyl ethers are highly stable and atom-economic protecting groups (PGs), but demand harsh and hazardous conditions for removal, limiting their utility. Consequently, there is a high demand for biocatalysts as milder, selective, and scalable alternatives, which can be met by a class of heme-thiolate enzymes: unspecific peroxygenases (UPOs). Herein, we report the identification of UPO23 in a commercial enzyme panel as a robust biocatalyst for -dealkylation reactions. UPO23 exhibited a broad substrate scope and efficiently removed methyl, ethyl, propyl, or allyl groups from protected primary, secondary, tertiary, and benzylic alcohols under ambient conditions. Mechanistic investigations revealed dual reaction pathways for UPO23, hydroxylating either the α-carbon of the alkyl chain of the PG or the substrate scaffold, explaining the formation of deprotected target alcohols as well as further oxidized products. Optimized reaction conditions reduced reaction times from 4 h to 15 min for methyl protected key substrates. Preparative scale reactions with protected benzyl ethers yielded up to 92% of the isolated alcohol products. These findings highlight the versatility of UPO23 and offer scalable, environmentally benign, and enzyme-based deprotection strategies for multistep organic synthesis.

Growing environmental concerns have led to a need for the reduction of CO emissions and the search for alternative fuels. The synthesis of methanol via the CO hydrogenation reaction provides a promising approach for these tasks. Promoting the existing Cu-based catalysts with Ga might be an option to create more effective catalysts. Here, size-controlled bimetallic CuGa nanoparticles (NPs) supported on either SiO or ZnO were synthesized to study the nature of the interaction of Cu and Ga. Operando spectroscopy and diffraction characterization methods (XPS, XAS, XRD) were employed to establish structure, chemical composition, and reactivity correlations. We find that Ga stays oxidized under the reaction conditions and segregates to the surface. For the CuGa NPs/ZnO, the dominating interaction of Cu with ZnO inhibits the promoting effect of Ga. Only on the inert SiO support, the beneficial influence of Ga is visible. Furthermore, high pretreatment temperatures were found to result in a favorable Cu-Ga interaction by partially reducing Ga, which is beneficial for methanol selectivity.

Selective multiboration including di- and triboration and hydroboration of alkynes and alkenes face significant challenges in organic synthesis, including achieving high regioselectivity, functional group tolerance, and catalyst stability while requiring mild conditions to maintain reactivity. These transformations have been predominantly explored by using homogeneous catalysts. In this study, we report the scalable synthesis of heterogeneous platinum single-atom catalyst (Pt-SAC) supported on ultrathin nanosheets of graphitic carbon nitride via a rapid microwave-assisted method. The Pt-SAC enables 1,2-diboration of sterically hindered alkenes and 1,2,2-triboration of alkynes with Bpin under mild conditions. For the diboration of styrene, the catalyst achieves 99% yield with 95% selectivity, a turnover number (TON) of 3711, and a turnover frequency (TOF) of 247 h. The catalyst also promotes the regioselective hydroboration of alkenes and alkynes, yielding -Markovnikov alkylboranes and vinylboranes, respectively. Computational calculations reveal that the enhanced reactivity on the Pt-SAC catalyst arises from adsorption-induced weakening of key bonds (C=C and B-H), thereby significantly lowering the activation energy barriers. The Pt-SAC exhibits stability and recyclability, maintaining performance over at least eight consecutive runs without detectable Pt leaching. This study highlights the potential of Pt-SAC as a robust and versatile platform for organoboron transformations under mild conditions, with relevance to applications in pharmaceutical, agrochemical, and polymer synthesis.

The increasing demand for hydrogen production has driven interest in ammonia decomposition. Iron-based catalysts, widely used for ammonia synthesis, exhibit suboptimal performance in the reverse process due to their tendency to form iron nitrides. Recent experiments have shown that alloying iron with cobalt enhances the catalytic activity (Chen et al., 15, 871, 2024), yet the microscopic origin of this promotional effect is not fully understood. To address this, we leverage recent developments in machine learning-based molecular dynamics simulations to investigate the key reactions of the catalytic cycle, fully accounting for dynamical lateral interactions on the catalyst surface. Our simulations reveal that cobalt alloying provides a dual promotional effect: it slightly lowers the free energy barrier for nitrogen recombination, which is the rate-determining step for ammonia decomposition on iron, while significantly suppressing nitrogen migration into the bulk, thereby preventing nitride formation. These insights are supported by complementary transient decomposition experiments and desorption measurements, which confirm the enhanced activity and resistance to nitridation in FeCo alloys compared to monometallic iron catalysts. Furthermore, long-term stability tests demonstrate that the FeCo catalyst sustains high ammonia conversion over extended time scales. By capturing the complex interplay of competing dynamical processes at the atomic scale, our results highlight the importance of going beyond static structure-property relationships to gain mechanistic insights that can guide the rational design of more robust and efficient catalysts.

Bimetallic catalysts featuring noble metals alloyed with non-noble metals have been widely employed to tune the catalytic reactivity and selectivity of hydrogenation reactions. The origins of catalytic enhancement for bimetallic nanoparticles compared to their monometallic counterparts often stem from an array of convoluted structural factors including electronic and geometric modifications to the active site ensemble as well as cooperativity arising from the presence of two metal atoms. In this work, we utilize colloidal synthesis of Pt-Cu alloy nanoparticles coupled to chemical and thermal ligand removal methods to tailor the local surface ensemble and oxidation state of the bimetallic catalyst. In doing so, we aim to elucidate the structural and mechanistic origins of stereoselectivity for the OH-directed olefin hydrogenation reaction, a reaction that has important implications in pharmaceutical synthesis. Through detailed surface characterization using CO DRIFTS, kinetic studies on directing and non-directing substrates, and computational modeling, we show that bidentate adsorption of the OH directing group to the Cu site and the olefin to the Pt site accelerates the rate of the directed reaction. Simultaneously, dilution of the Pt ensemble with Cu atoms suppresses the rate of the undirected reaction. These two structural factors combine in a PtCu alloy catalyst to enable hydrogenation turnover frequencies of ~10 h while maintaining a 92:8 diastereomeric ratio for the directed:undirected product. Impressively, the PtCu alloy achieves hydrogenation rates comparable to monometallic Pt while dramatically increasing the diastereoselectivity. The ability for Pt-Cu alloys to accelerate the hydrogenation of an olefin proximal to a directing group through OH adsorption could serve as a general strategy toward chemo- and stereoselective transformations of allylic and homoallylic alcohols.

Secondary -arylsulfonamides are common in pharmaceutical compounds owing to their valuable physicochemical properties. Direct -arylation of primary sulfonamides presents a modular approach to this scaffold but remains a challenging disconnection for transition metal-catalyzed cross coupling broadly, including the Chan-Lam (CL) coupling of nucleophiles with (hetero)aryl boronic acids. Although the CL coupling reaction typically operates under mild conditions, it is also highly substrate-dependent and prone to over-arylation, limiting its generality and predictivity. To address these gaps, we employed data science tools in tandem with high-throughput experimentation to study and model the CL -arylation of primary sulfonamides. To minimize bias in training set design, we applied unsupervised learning to systematically select a diverse set of primary sulfonamides for high-throughput data collection and modeling, resulting in a novel dataset of 3,904 reactions. This workflow enabled us to identify broadly applicable, highly selective conditions for the CL coupling of aliphatic and (hetero)aromatic primary sulfonamides with complex organoboron coupling partners. We also generated a regression model that not only successfully identifies high-yielding conditions for the CL coupling of various sulfonamides, but also sulfonamide features that dictate reaction outcome.