Distinct Intermediates Research Articles

The Swi5-Sfr1 complex regulates Dmc1- and Rad51-driven DNA strand exchange proceeding through two distinct three-stranded intermediates by different mechanisms.

In eukaryotes, Dmc1 and Rad51 are key proteins of homologous recombination. The Swi5-Sfr1 complex in fission yeast, a conserved auxiliary factor, stimulates DNA strand exchange driven by both Dmc1 and Rad51. Interestingly, biochemical analysis suggested that Swi5-Sfr1 regulates strand exchange activities of these recombinases differently, but the mechanisms were unclear. We previously developed a real-time system to analyze Rad51-driven DNA strand exchange and identified two topologically distinct three-stranded intermediates (complex 1 (C1) and complex 2 (C2)). Swi5-Sfr1 facilitates the C1-C2 transition and releases single-stranded DNA (ssDNA) from C2, acting as a strand exchange activator. In this study, we investigated fission yeast Dmc1-driven DNA strand exchange and the role of Swi5-Sfr1 in Dmc1 activity in real-time. Kinetic analysis revealed a three-step model for the Dmc1-driven reaction, similar to that of Rad51. Although Swi5-Sfr1 stimulated the Dmc1-driven reaction, it had a weaker impact than Rad51. Furthermore, Swi5-Sfr1 enhanced the association of Dmc1 with ssDNA by promoting filament nucleus formation, acting as a mediator, unlike its role with Rad51. This stimulation mechanism also differs from that of Ca2+ or ATP analog, AMP-PNP. Our findings suggest that Swi5-Sfr1 stimulates strand exchange activities of Dmc1 and Rad51 via different reaction steps.

Chloramphenicol Interferes with 50S Ribosomal Subunit Maturation via Direct and Indirect Mechanisms.

Chloramphenicol (CAM), a well-known broad-spectrum antibiotic, inhibits peptide bond formation in bacterial ribosomes. It has been reported to affect ribosome assembly mainly through disrupting the balance of ribosomal proteins. The present study investigates the multifaceted effects of CAM on the maturation of the 50S ribosomal subunit in Escherichia coli (E. coli). Using label-free quantitative mass spectrometry (LFQ-MS), we observed that CAM treatment also leads to the upregulation of assembly factors. Further cryo-electron microscopy (cryo-EM) analysis of the ribosomal precursors characterized the CAM-treatment-accumulated pre-50S intermediates. Heterogeneous reconstruction identified 26 distinct pre-50S intermediates, which were categorized into nine main states based on their structural features. Our structural analysis highlighted that CAM severely impedes the formation of the central protuberance (CP), H89, and H58 during 50S ribosomal subunit maturation. The ELISA assay further demonstrated the direct binding of CAM to the ribosomal precursors, suggesting that the interference with 50S maturation occurs through a combination of direct and indirect mechanisms. These findings provide new insights into the mechanism of the action of CAM and provide a foundation for a better understanding of the assembly landscapes of the ribosome.

Spin States Matter─from Fundamentals toward Synthetic Methodology Development and Drug Discovery.

ConspectusThe potent reactivity of carbenes and nitrenes has been traditionally harnessed by the employment of a transition-metal catalyst in which the reactivity of the metal carbene/nitrene intermediates can be controlled via the judicious tuning of the metal catalyst. In recent years, progress made in this research area has unveiled novel strategies to directly access free carbenes or nitrenes under visible-light-mediated conditions without the necessity of a metal catalyst for stabilization of the carbene/nitrene intermediate. Such photochemical approaches present new opportunities to leverage orthogonal reactions with classic metal-catalyzed transformations.In this Account, we describe the major contributions from our group over the past years pushing the boundaries of light-mediated carbene and nitrene transfer reactions. In the first section, the development from purely singlet carbene chemistry toward methods that allow access to triplet carbene intermediates will be dissected. We describe how the triplet spin state of reagents provides a rich array of novel synthetic methods that build on the fundamentals of spin conservation. We lay out the different strategies in accessing the triplet spin state of carbenes (i.e., via electronic stabilization, via triplet sensitization with suitable photocatalysts, or via exploitation of geometric features of these intermediates), followed by an analysis of how the triplet spin state can be employed to leverage reactions distinct to the classic singlet carbene chemistry.The second part focuses on free nitrene intermediates, whereby both photochemical and photocatalytic strategies are analyzed and compared. We initiate with a discussion of the reactivity of iminoiodinanes as nitrene precursors in the presence of a photocatalyst or under photochemical conditions and how these two approaches result in fundamentally distinct nitrogen-based intermediates. While a nitrene radical anion is formed under photocatalytic conditions, triplet nitrene is generated under photochemical conditions. We commence with an outline of the basic reactivity of nitrene transfer reactions under both conditions, with a focus on the reaction with substrates containing double bonds. Finally, the latest developments in advanced cycloaddition chemistry beyond classic aziridination reactions are examined, with a special emphasis on the relay of the triplet nitrene reactivity to enable a Pauson-Khand-like (2 + 2 + 1) cycloaddition reaction that offers convenient access to high value bioisosteres in drug discovery.The work from our group on spin-dependent reactivities offers insight into important fundamentals in synthesis, where the spin state of the reactive intermediate will dictate the reaction outcome. We hope this may inspire others to widen the scope of applications of light-mediated carbene and/or nitrene transfer reactions, and furthermore, we anticipate that these understandings may also enable the development of advanced catalytic systems featuring triplet metal carbene/nitrene intermediates.

Molecular Solvation Environment Controls the Active Site in Cation-Mediated Electrocatalytic CO2 Reduction to Methanol

Electrocatalytic synthesis of higher-value products from waste molecules is an emerging technique for sustainable chemical catalysis. Heterogeneous molecular electrocatalysts are an important group of materials where the catalytic activity and selectivity can be controlled using molecularly defined active sites. Despite extensive efforts to synthesize better molecular catalysts, the effects of molecular aggregation, which dominates the interaction of the catalyst with the electrode surface as well as with the electrochemical solvation environment, are not fully understood. Using cobalt phthalocyanine (CoPc) dispersed on carbon nanotubes (CNTs) as a model system, we find that controlling the direct interaction of the molecular catalyst with cations in the electrochemical double layer (EDL) results in significantly enhanced performance for CO2 reduction (CO2RR). Specifically, molecular dispersion of the CoPc onto CNTs yields a 4-fold increase in total current density and 8-fold increase in methanol (MeOH) selectivity compared to aggregated CoPc physically mixed with the same CNT support, enabling CO2 to MeOH conversion with 42.34% Faradaic efficiency (FE). Using surface-selective sum-frequency generation (SFG) vibrational spectroscopy, direct detection of reaction intermediates reveals that the potential-dependent adsorption of two distinct CO intermediates at two types of active sites, one less active and producing mostly CO, the other more active and able to produce methanol. DFT calculations show that the CO intermediate responsible for selective MeOH production results from the direct interaction with cations present in the EDL. This interaction, which is only possible when CoPc is molecularly dispersed on the electrode surface, is responsible for the cation-assisted conversion of CO to MeOH. Control experiments using either strongly hydrated Li+, or chelated K+ by 18-crown-6-ether, which suppress MeOH formation, further confirms the important role of this interaction. Similarly significant enhancement effects are also observed for nitrate reduction reaction (NO3RR) and oxygen reduction reaction (ORR), showing that dispersing molecular catalysts into monomers states is a general design parameter required to enhance activity and selectivity by cation-assisted reaction kinetics inside the EDL.

Interfacial adsorption and catalysis of single-atom Pt-loaded ZrO2 surfaces for enhancing formaldehyde oxidation

The emerging transition metal single-atom catalysts (SACs) are expected to have high activity for converting detrimental formaldehyde (HCHO) under mild conditions. Currently, the exploitation of novel SACs with designed or modified support surfaces remains largely imperative. Herein, we used density functional theory to explore the catalytic performance for HCHO oxidation on various single-atom Pt-loaded ZrO2 surfaces, in which oxygen vacancy and lattice hydroxyl group were included on the surfaces. The surface modifications could enhance the co-adsorption of HCHO and O2 molecules and provide more active sites due to interfacial electron redistribution. The transition state search approach was applied to investigate the oxidation pathways on various ZrO2-supported SAC surfaces, wherein distinct dehydrogenation mechanisms and intermediates were clarified. The oxygen vacancy defects and hydroxyl groups can enhance the catalytic activity for HCHO oxidation by providing active receptor sites for the H-transfer and facilitating the CH bond breakage. Microkinetic modeling was further used to characterize the reaction rates and kinetics behavior of HCHO oxidation on the SAC surfaces. Our simulation demonstrates the excellent catalytic performance of the modified ZrO2-supported SAC in the HCHO oxidation. Meanwhile, the mechanism is also an important implication for the synthesis and design of novel SACs.

Critical roles of soil composition and pollutant properties on the degradation of PPCPs during ferrous/persulfate processes

Pharmaceuticals and personal care products (PPCPs) are widely used worldwide and cause potential soil pollution. Fe2+-activated persulfate (PS) processes (Fe-PAPs) are promising techniques for soil remediation. However, a knowledge gap exists in the mechanistic insights into the dominant factors affecting the degradation of different PPCPs in varied soil types. This study systematically investigated the roles of soil components and pollutant properties in the degradation of three PPCPs (triclosan (TCS), triclocarban (TCC), and naproxen (NPS)) in the nine soils in the Fe2+/PS system. The degradation efficiencies of TCS and NPS ranged from 10.92 % to 91.62 % and 46.59 % to 99.81 %, respectively, whereas nearly no degradation was observed for TCC. PPCPs with high water solubility, high energies of the highest occupied molecular orbital (EHOMO), low pKa values, low energy gap (ΔE), or low vertical ionization potential (VIP) were more favorable for degradation. XPS analysis suggested that aliphatic carbon (Ali–C–C(H)), ether or alcohol carbon (C–O), and aldehyde or ketonic carbon (CO) on SOM significantly inhibited TCS degradation. The results of ROS quenching experiments showed that SO4•− and 1O2 played major roles in TCS and NPS degradation in the six soils, with the relative contributions ranged from 24.82 % to 99.14 % and 0.15 % to 73.40 %, respectively. The interaction between soil components, active species, and pollutants resulted in the distinct intermediates of TCS and NPS in different soils. Our findings provide in-depth insights into the role of soil composition and pollutant properties on the remediation of PPCP-contaminated soils in Fe-PAPs.

Synthesis and utility of N-boryl and N-silyl enamines derived from the hydroboration and hydrosilylation of N-heteroarenes and N-conjugated compounds.

Catalytic hydroboration and hydrosilylation have emerged as promising strategies for the reduction of unsaturated hydrocarbons and carbonyl compounds, as well as for the dearomatization of N-heteroarenes. Various catalysts have been employed in these processes to achieve the formation of reduced products via distinct reaction pathways and intermediates. Among these intermediates, N-silyl enamines and N-boryl enamines, which are derived from hydrosilylation and hydroboration, are commonly underestimated in this reduction process. Because these versatile intermediates have recently been utilized in situ as nucleophilic reagents or dipolarophiles for the synthesis of diverse molecules, an expeditious review of the synthesis and utilization of N-silyl and N-boryl enamines is crucial. In this review, we comprehensively discuss a wide range of hydrosilylation and hydroboration catalysts used for the synthesis of N-silyl and N-boryl enamines. These catalysts include main-group metals (e.g., Mg and Zn), transition metals (e.g., Rh, Ru, and Ir), earth-abundant metals (e.g., Fe, Co, and Ni), and non-metal catalysts (including P, B, and organocatalysts). Furthermore, we highlight recent research efforts that have leveraged these versatile intermediates for the synthesis of intriguing molecules, offering insights into future directions for these invaluable building blocks.

Metabolism of toxic benzonitrile and hydroxybenzonitrile isomers via several distinct central pathway intermediates in a catabolically robust Burkholderia sp.

Aromatic nitriles are of considerable environmental concern, because of their hazardous impacts on the health of both humans and wildlife. In the present study, Burkholderia sp. strain BC1 was observed to be capable of utilizing toxic benzonitrile and hydroxybenzonitrile isomers singly, as sole carbon and energy sources. The results of chromatographic and spectrometric analyses in combination with oxygen uptake and enzyme activity studies, revealed the metabolism of benzonitrile as well as 2-, 3-, and 4-hydroxybenzonitriles by nitrile hydratase-amidase to the corresponding carboxylates. These carboxylates were further metabolized via central pathways, namely benzoate-catechol, salicylate-catechol, 3-hydroxybenzoate-gentisate and 4-hydroxybenzoate-protocatechute pathways in strain BC1, ultimately leading to the TCA cycle intermediates. Studies also evaluated substrate specificity profiles of both nitrile hydratase and amidase(s) involved in the denitrification of the nitriles. In addition, a few metabolic crosstalk events due to the induction of multiple operons by central metabolites were appraised in strain BC1. The present study illustrates the broad degradative potential of strain BC1, harboring diverse catabolic machinery of biotechnological importance, elucidating pathways for the assimilation of benzonitrile and that of hydroxybenzonitrile isomers for the first time.

Involvement of Escherichia coli YbeX/CorC in ribosomal metabolism.

YbeX of Escherichia coli, a member of the CorC protein family, is encoded in the same operon with ribosome-associated proteins YbeY and YbeZ. Here, we report the involvement of YbeX in ribosomal metabolism. The ΔybeX cells accumulate distinct 16S rRNA degradation intermediates in the 30S particles and the 70S ribosomes. E. coli lacking ybeX has a lengthened lag phase upon outgrowth from the stationary phase. This growth phenotype is heterogeneous at the individual cell level and especially prominent under low extracellular magnesium levels. The ΔybeX strain is sensitive to elevated growth temperatures and to several ribosome-targeting antibiotics that have in common the ability to induce the cold shock response in E. coli. Although generally milder, the phenotypes of the ΔybeX mutant overlap with those caused by ybeY deletion. A genetic screen revealed partial compensation of the ΔybeX growth phenotype by the overexpression of YbeY. These findings indicate an interconnectedness among the ybeZYX operon genes, highlighting their roles in ribosomal assembly and/or degradation.

Mechanism of proton-powered c-ring rotation in a mitochondrial ATP synthase

Proton-powered c-ring rotation in mitochondrial ATP synthase is crucial to convert the transmembrane protonmotive force into torque to drive the synthesis of adenosine triphosphate (ATP). Capitalizing on recent cryo-EM structures, we aim at a structural and energetic understanding of how functional directional rotation is achieved. We performed multi-microsecond atomistic simulations to determine the free energy profiles along the c-ring rotation angle before and after the arrival of a new proton. Our results reveal that rotation proceeds by dynamic sliding of the ring over the a-subunit surface, during which interactions with conserved polar residues stabilize distinct intermediates. Ordered water chains line up for a Grotthuss-type proton transfer in one of these intermediates. After proton transfer, a high barrier prevents backward rotation and an overall drop in free energy favors forward rotation, ensuring the directionality of c-ring rotation required for the thermodynamically disfavored ATP synthesis. The essential arginine of the a-subunit stabilizes the rotated configuration through a salt bridge with the c-ring. Overall, we describe a complete mechanism for the rotation step of the ATP synthase rotor, thereby illuminating a process critical to all life at atomic resolution.

Oxygen Activation in Aromatic Ring Cleaving Salicylate Dioxygenase: Detection of Reaction Intermediates with a Nitro-substituted Substrate Analog.

Cupin dioxygenases such as salicylate 1,2-dioxygense (SDO) perform aromatic C-C bond scission via a 3-His motif tethered iron cofactor. Here, transient kinetics measurements are used to monitor the catalytic cycle of SDO by using a nitro-substituted substrate analog, 3-nitrogentisate. Compared to the natural substrate, the nitro group reduces the enzymatic kcat by 500-fold, thereby facilitating the detection and kinetic characterization of reaction intermediates. Sums and products of reciprocal relaxation times derived from kinetic measurements were found to be linearly dependent on O2 concentration, suggesting reversible formation of two distinct intermediates. Dioxygen binding to the metal cofactor takes place with a forward rate of 5.9×103 M-1 s-1: two orders of magnitude slower than other comparable ring-cleaving dioxygenses. Optical chromophore of the first intermediate is distinct from the in situ generated SDO Fe(III)-O2⋅- complex but closer to the enzyme-substrate precursor.

In situ single-molecule investigations of the impacts of biochemical perturbations on conformational intermediates of monomeric α-synuclein.

α-Synuclein aggregation is a common trait in synucleinopathies, including Parkinson's disease. Being an unstructured protein, α-synuclein exists in several distinct conformational intermediates, contributing to both its function and pathogenesis. However, the regulation of these monomer conformations by biochemical factors and potential drugs has remained elusive. In this study, we devised an in situ single-molecule manipulation approach to pinpoint kinetically stable conformational intermediates of monomeric α-synuclein and explore the effects of various biochemical factors and drugs. We uncovered a partially folded conformation located in the non-amyloid-β component (NAC) region of monomeric α-synuclein, which is regulated by a preNAC region. This conformational intermediate is sensitive to biochemical perturbations and small-molecule drugs that influencing α-synuclein's aggregation tendency. Our findings reveal that this partially folded intermediate may play a role in α-synuclein aggregation, offering fresh perspectives for potential treatments aimed at the initial stage of higher-order α-synuclein aggregation. The single-molecule approach developed here can be broadly applied to the study of disease-related intrinsically disordered proteins.

Heteromeric Completive Self-Sorting in Coordination Cage Systems.

Heteroleptic coordination cages, nonstatistically assembled from a set of matching ligands, can be obtained by mixing individual components or via cage-to-cage transformations from homoleptic precursors. Based on the latter approach, we here describe a new level of self-sorting in coordination cage systems, namely, 'heteromeric completive self-sorting'. Here, two heteroleptic assemblies of type Pd2A2B2 and Pd2A2C2, sharing one common ligand component A but differing in the other, are shown to coexist in solution. This level of self-sorting can be reached either from a statistical mixture of assemblies based on some ligands B and C or, alternatively, following a first step of integrative self-sorting giving a distinct Pd2B2C2 intermediate. While subtle enthalpic factors dictate the outcome of the self-sorting, we found that it is controllable. From a unique set of three ligands, we demonstrate the transition from strict integrative self-sorting forming a Pd2AB2C cage to heteromeric completive self-sorting to give Pd2A2B2 and Pd2A2C2 by variation of the ligand ratio. Cage-to-cage transformations were followed by NMR and MS experiments. Single crystal X-ray structures for three new heteroleptic cages were obtained, impressively highlighting the versatility of ligand A to either form a π-stacked trans-figure-of-eight arrangement in Pd2A2B2 or occupy two cis-edges in Pd2A2C2 or only a single edge in Pd2AB2C. This study paves the way toward the control of heteroleptic cage populations in a systems chemistry context with emerging features such as chemical information processing, adaptive guest selectivity, or stimuli-responsive catalytic action.

Structural basis of ribosomal 30S subunit degradation by RNase R.

Protein synthesis is a major energy-consuming process of the cell that requires the controlled production1-3 and turnover4,5 of ribosomes. Although the past few years have seen major advances in our understanding of ribosome biogenesis, structural insight into the degradation of ribosomes has been lacking. Here we present native structures of two distinct small ribosomal 30S subunit degradation intermediates associated with the 3' to 5' exonuclease ribonuclease R (RNase R). The structures reveal that RNase R binds at first to the 30S platform to facilitate the degradation of the functionally important anti-Shine-Dalgarno sequence and the decoding-site helix 44. RNase R then encounters a roadblock when it reaches the neck region of the 30S subunit, and this is overcome by a major structural rearrangement of the 30S head, involving the loss of ribosomal proteins. RNase R parallels this movement and relocates to the decoding site by using its N-terminal helix-turn-helix domain as an anchor. In vitro degradation assays suggest that head rearrangement poses a major kinetic barrier for RNase R, but also indicate that the enzyme alone is sufficient for complete degradation of 30S subunits. Collectively, our results provide a mechanistic basis for the degradation of 30S mediated by RNase R, and reveal that RNase R targets orphaned 30S subunits using a dynamic mechanism involving an anchored switching of binding sites.

Two-Dimensional Nonbenzenoid Heteroacene Crystals Synthesized via In-Situ Embedding of Ladder Bipyrazinylenes on Au(111).

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

Dual-Catalyzed Stereodivergent Electrooxidative Homocoupling of Benzoxazolyl Acetate.

The development of a reliable strategy for stereodivergent radical reactions that allows convenient access to all stereoisomers of homocoupling adducts with multiple stereogenic centers remains an unmet goal in organic synthesis. Herein, we describe a dual-catalyzed electrooxidative C(sp3)-H/C(sp3)-H homocoupling with complete absolute and relative stereocontrol for the synthesis of molecules with contiguous quaternary stereocenters in a general and predictable manner. The stereodivergent electrooxidative homocoupling reaction is achieved by synergistically utilizing two distinct chiral catalysts that convert identical racemic substrates into inherently distinctive reactive chiral intermediates, dictate enantioselective radical addition, and allow access to the full complement of stereoisomeric products via simple catalyst permutation. The successful execution of the dual-electrocatalytic strategy programmed via electrooxidative activation provides a significant conceptual advantage and will serve as a useful foundation for further research into cooperative stereocontrolled radical transformations and diversity-oriented synthesis.

Insights into the nucleation and growth of BiOCl nanoparticles by in situ X-ray pair distribution function analysis and in situ liquid cell TEM.

The synthesis of bismuth oxyhalides as defined nanostructures is hindered by their fast nucleation and growth in aqueous solutions. Using our recently developed single-source precursor, the formation of bismuth oxychloride in such solutions can be slowed significantly. As reported herein, this advance enables BiOCl formation to be investigated by in situ X-ray total scattering and in situ liquid cell transmission electron microscopy. In situ pair distribution function analysis of X-ray total scattering data reveals the local order of atomic structures throughout the synthesis, while in situ liquid cell transmission electron microscopy allows for tracking the growth of individual nanoparticles. Through this work, the precursor complex is shown to give rise to BiOCl upon heating in solution without the observation of structurally distinct intermediates. The emerging nanoparticles have a widened interlayer spacing, which moderately decreases as the particles grow. Mechanistic insights into the formation of bismuth oxyhalide nanoparticles, including the absence of distinct intermediates within the available time resolution, will help facilitate future design of controlled BiOX nanostructures.

Palladium-Catalyzed Electrooxidative Double C-H Arylation.

The electrochemical transition metal-catalyzed cross-dehydrogenative reaction has emerged as a promising platform to achieve a sustainable and atom-economic organic synthesis that avoids hazardous oxidants and minimizes undesired byproducts and circuitous functional group operations. However, a poor mechanistic understanding still prevents the widespread adoption of this strategy. In this regard, we herein present an electrochemical palladium-catalyzed oxidative coupling strategy to access biaryls in the absence of a stoichiometric chemical oxidant. The robust palladaelectrocatalysis considerably suppresses the occurrence of homocoupling and oxygenation, being compatible even with electron-deficient arenes. Late-stage functionalization and Boscalid precursor synthesis further highlighted the practical importance of our electrolysis. Remarkably, mechanistic studies including the evaluation of the reaction order of each component by variable time normalization analysis (VTNA) and initial rate analysis, H/D exchange experiment, kinetic isotope effect, and stoichiometric organometallic experiments provided strong support for the involvement of transmetalation between two organopalladium complexes in the turnover limiting step. Therefore, matching the concentrations or lifetimes of two distinct organopalladium intermediates is revealed to be a pivot to the success of electrooxidative catalysis. Moreover, the presence of cationic copper(II) seems to contribute to the stabilization of the palladium(0) catalyst instead of playing a role in the oxidation of the catalyst.

Unveiled the Structure-Selectivity Relationship for Carbon Dioxide Reduction Triggered by Bi-Doped Cu-Based Nanocatalysts.

To investigate synergistic effect between geometric and electronic structures on directing CO2RR selectivity, water phase synthetic protocol and surface architecture engineering strategy are developed to construct monodispersed Bi-doped Cu-based nanocatalysts. The strongly correlated catalytic directionality and Bi3+ dopant can be rationalized by the regulation of [*COOH]/[*CO] adsorption capacities through the appropriate doping of Bi3+ electronic modulator, resulting in volcano relationship between FECO/TOFCO and surface EVBM values. Spectroscopic study reveals that the dual-site binding mode ([Cu─μ─C(═O)O─Bi3+]) enabled by Cu1Bi3+ 2 motif in single-phase Cu150Bi1 nanocatalyst drives CO2-to-CO conversion. In contrast, the study of dynamic Bi speciation and phase transformation in dual-phase Cu50Bi1 nanocatalyst unveils that the Bi0-Bi0 contribution emerges at the expense of BOC phase, suggesting metallic Bi0 phase acting as [H]˙ formation center switches CO2RR selectivity toward CO2-to-HCOO- conversion via [*OCHO] and [*OCHOK] intermediates. This work provides significant insight into how geometric architecture cooperates with electronic effect and catalytic motif/phase to guide the selectivity of electrocatalytic CO2 reduction through the distinct surface-bound intermediates and presents molecular-level understanding of catalytic mechanism for CO/HCOO- formation.

Origins of Selectivity in Glycosylation Reactions with Saccharosamine Donors.

A combination of DFT calculations and experiments is used to describe how the selection of a promoter can control the stereochemical outcome of glycosylation reactions with the deoxy sugar saccharosamine. Depending on the promoter, either α- or β-linked reactive intermediates are formed. These studies show that differential modes of activation lead to the formation of distinct intermediates that undergo highly selective reactions through an SN2-like mechanism.