JACS Au最新文献

Carbohydrates are biologically and medicinally important molecules that are attracting growing attention to their synthesis and applications. Unlike the biosynthetic processes for nucleic acids and proteins, carbohydrate biosynthesis is not template-driven, more challenging, and often leads to product variations. In lieu of templates for carbohydrate biosynthesis, we describe herein a new concept of designing enzyme assembly synthetic maps (EASyMaps) as blueprints to guide glycosyltransferase-dependent stepwise one-pot multienzyme (StOPMe) synthesis to systematically access structurally diverse carbohydrates in a target-oriented manner. The strategy is demonstrated for the construction of a comprehensive library of tetraose-core-containing human milk oligosaccharides (HMOs) presenting diverse functional important glycan epitopes shared by more complex HMOs. The tetraose-core-HMOs are attractive candidates for large-scale production and for the development of HMO-based nutraceuticals. To achieve the preparative-scale synthesis of targets containing a Neu5Acα2-6GlcNAc component, a human α2-6-sialyltransferase hST6GALNAC5 is successfully expressed in E. coli. Neoglycoproteins with controlled glycan valencies are prepared and immobilized on fluorescent magnetic beads. Multiplex bead assays reveal ligands of glycan-binding proteins from plants, influenza viruses, human, and bacteria, identifying promising HMO targets for functional applications. The concept of designing EASyMaps as blueprints to guide StOPMe synthesis in a systematic target-oriented manner is broadly applicable beyond the synthesis of HMOs. The efficient StOPMe process is suitable for the large-scale production of complex carbohydrates and can be potentially adapted for automation.

Carbohydrates are biologically and medicinally important molecules that are attracting growing attention to their synthesis and applications. Unlike the biosynthetic processes for nucleic acids and proteins, carbohydrate biosynthesis is not template-driven, more challenging, and often leads to product variations. In lieu of templates for carbohydrate biosynthesis, we describe herein a new concept of designing enzyme assembly synthetic maps (EASyMaps) as blueprints to guide glycosyltransferase-dependent stepwise one-pot multienzyme (StOPMe) synthesis to systematically access structurally diverse carbohydrates in a target-oriented manner. The strategy is demonstrated for the construction of a comprehensive library of tetraose-core-containing human milk oligosaccharides (HMOs) presenting diverse functional important glycan epitopes shared by more complex HMOs. The tetraose-core-HMOs are attractive candidates for large-scale production and for the development of HMO-based nutraceuticals. To achieve the preparative-scale synthesis of targets containing a Neu5Acα2–6GlcNAc component, a human α2–6-sialyltransferase hST6GALNAC5 is successfully expressed in E. coli. Neoglycoproteins with controlled glycan valencies are prepared and immobilized on fluorescent magnetic beads. Multiplex bead assays reveal ligands of glycan-binding proteins from plants, influenza viruses, human, and bacteria, identifying promising HMO targets for functional applications. The concept of designing EASyMaps as blueprints to guide StOPMe synthesis in a systematic target-oriented manner is broadly applicable beyond the synthesis of HMOs. The efficient StOPMe process is suitable for the large-scale production of complex carbohydrates and can be potentially adapted for automation.

Electro-upgrading of low-cost alcohols such as ethylene glycol is a promising and sustainable approach for the production of value-added chemicals while substituting energy-consuming OER in water splitting. However, the sluggish kinetics and possibility of C–C dissociation make the design of selective and efficient electrocatalysts challenging. Herein, we demonstrate the synthesis of a hollowed bimetallic PtAg nanostructure through an in situ dynamic evolution method that could efficiently drive the selective electrochemical ethylene glycol oxidation reaction (EGOR). The resulting mild surficial oxidation has intrinsically improved EGOR activity, exhibiting a remarkable performance toward glycolate (selectivity up to 99.2% and faradic efficiency ∼97%) at high current density with low overpotential (355 mA·cm^–2 at 1.0 V, 16.3 A·mg_Pt^–1), exceeding prior outcomes. Through comprehensive operando characterization and theoretical calculations, this study systematically reveals that the in situ formation of Pt–O(H)_ad is pivotal for modulating the electronic structure of surface and facilitating the selective electrooxidation and adsorption of −CH₂OH. The competitive C–C dissociation pathway toward HCOO^– is concurrently inhibited in comparison to Pt. An industrial-level current coupled with hydrogen production at low cell voltages was also achieved. These findings offer more in-depth mechanistic understanding of the EGOR’s reaction pathway mediated by surface environment in Pt-based electrocatalysts.

Electro-upgrading of low-cost alcohols such as ethylene glycol is a promising and sustainable approach for the production of value-added chemicals while substituting energy-consuming OER in water splitting. However, the sluggish kinetics and possibility of C-C dissociation make the design of selective and efficient electrocatalysts challenging. Herein, we demonstrate the synthesis of a hollowed bimetallic PtAg nanostructure through an in situ dynamic evolution method that could efficiently drive the selective electrochemical ethylene glycol oxidation reaction (EGOR). The resulting mild surficial oxidation has intrinsically improved EGOR activity, exhibiting a remarkable performance toward glycolate (selectivity up to 99.2% and faradic efficiency ∼97%) at high current density with low overpotential (355 mA·cm^-2 at 1.0 V, 16.3 A·mg_Pt ^-1), exceeding prior outcomes. Through comprehensive operando characterization and theoretical calculations, this study systematically reveals that the in situ formation of Pt-O(H)_ad is pivotal for modulating the electronic structure of surface and facilitating the selective electrooxidation and adsorption of -CH₂OH. The competitive C-C dissociation pathway toward HCOO^- is concurrently inhibited in comparison to Pt. An industrial-level current coupled with hydrogen production at low cell voltages was also achieved. These findings offer more in-depth mechanistic understanding of the EGOR's reaction pathway mediated by surface environment in Pt-based electrocatalysts.

The activation of H₂ on NaY-encapsulated Mo sulfide clusters is significantly influenced by the presence of Ni at ion exchange positions. Ni was incorporated by partially ion exchanging the NaY zeolite with Ni²⁺ cations. Mo(CO)₆ vapors were subsequently deposited on the ion exchanged NiNaY zeolites followed by sulfidation in 10 vol % H₂S/H₂ at 673 K, leading to the formation of dimeric Mo₂S₄ clusters connected to Ni²⁺ via bridging S atoms. In contrast to the monometallic Mo sulfide clusters, which stabilize adsorbed hydrogen primarily as hydrides on Mo atoms, the bimetallic Ni-Mo sulfide clusters bind hydrogen also as sulfhydryl groups on the bridging sulfur atoms. The formation of sulfhydryl groups in Ni-Mo sulfide clusters is attributed to the lower electron density on the cluster due to coordination with more electronegative Ni²⁺. The ethene hydrogenation rate was significantly higher on the bimetallic Ni-Mo sulfide catalysts compared to monometallic Mo sulfide catalysts because the stabilization of atomic hydrogen as sulfhydryl groups opens a new hydrogenation pathway.

Methods that assemble multiple peptide disulfide bonds in the solid phase (pseudodilute conditions) are in high demand for synthesizing disulfide-rich peptides. Yet, the existing repertoire of disulfide-forming orthogonal chemistries in the solid phase is often hindered by additional steps for protecting group removals as well as the absolute necessity of rare, customized orthogonal cysteine (Cys) building blocks. We now describe a conceptually new while operationally simple on-resin method for disulfide assembly with widely accessible Cys protecting groups (Trt, Acm, and ^t Bu) using acid-activated N-chlorosuccinimide (NCS) in a single step. In the process, S- ^t Bu Cys emerged as a new orthogonal building block for the single-step assembly of the peptide disulfide. In our investigations, 2% TFA-activated NCS offered rapid (∼15 min) and a clean disulfide product in various peptides. Eventually, this novel strategy (2% TFA-NCS) was strategically merged in stepwise cross-linking with our previously described I₂/S₂O₈ ^2--mediated disulfide assembly protocol to leverage two regioselective disulfide bonds into conotoxin, gomesin, and a de novo sequence within ∼30 min. Invariably, this new method proved highly productive and operationally simple. DFT calculations also support the hypothesis of NCS activation that assists efficient disulfide assembly in crossing a low-lying energy barrier via sulfonium intermediates. This newly developed method for ^t Bu deprotection and concomitant disulfide assembly in the solid phase should find wide applications in de novo peptide disulfide synthesis.

Methods that assemble multiple peptide disulfide bonds in the solid phase (pseudodilute conditions) are in high demand for synthesizing disulfide-rich peptides. Yet, the existing repertoire of disulfide-forming orthogonal chemistries in the solid phase is often hindered by additional steps for protecting group removals as well as the absolute necessity of rare, customized orthogonal cysteine (Cys) building blocks. We now describe a conceptually new while operationally simple on-resin method for disulfide assembly with widely accessible Cys protecting groups (Trt, Acm, and ^tBu) using acid-activated N-chlorosuccinimide (NCS) in a single step. In the process, S-^tBu Cys emerged as a new orthogonal building block for the single-step assembly of the peptide disulfide. In our investigations, 2% TFA-activated NCS offered rapid (∼15 min) and a clean disulfide product in various peptides. Eventually, this novel strategy (2% TFA-NCS) was strategically merged in stepwise cross-linking with our previously described I₂/S₂O₈^2–-mediated disulfide assembly protocol to leverage two regioselective disulfide bonds into conotoxin, gomesin, and a de novo sequence within ∼30 min. Invariably, this new method proved highly productive and operationally simple. DFT calculations also support the hypothesis of NCS activation that assists efficient disulfide assembly in crossing a low-lying energy barrier via sulfonium intermediates. This newly developed method for ^tBu deprotection and concomitant disulfide assembly in the solid phase should find wide applications in de novo peptide disulfide synthesis.

The activation of H₂ on NaY-encapsulated Mo sulfide clusters is significantly influenced by the presence of Ni at ion exchange positions. Ni was incorporated by partially ion exchanging the NaY zeolite with Ni²⁺ cations. Mo(CO)₆ vapors were subsequently deposited on the ion exchanged NiNaY zeolites followed by sulfidation in 10 vol % H₂S/H₂ at 673 K, leading to the formation of dimeric Mo₂S₄ clusters connected to Ni²⁺ via bridging S atoms. In contrast to the monometallic Mo sulfide clusters, which stabilize adsorbed hydrogen primarily as hydrides on Mo atoms, the bimetallic Ni–Mo sulfide clusters bind hydrogen also as sulfhydryl groups on the bridging sulfur atoms. The formation of sulfhydryl groups in Ni–Mo sulfide clusters is attributed to the lower electron density on the cluster due to coordination with more electronegative Ni²⁺. The ethene hydrogenation rate was significantly higher on the bimetallic Ni–Mo sulfide catalysts compared to monometallic Mo sulfide catalysts because the stabilization of atomic hydrogen as sulfhydryl groups opens a new hydrogenation pathway.

5-Thioglycopyranosyl donors differ in reactivity and selectivity from simple glycopyranosyl donors. An extensive study has been conducted on the nature and stability of the reactive intermediates generated on the activation of per-O-acetyl and per-O-methyl 5-thioglucopyranosyl donors and the corresponding glucopyranosyl donors. Variable temperature nuclear magnetic resonance (NMR) studies with per-O-methylated or per-O-acetyl glycosyl sulfoxides and trichloroacetimidates on activation with trifluoromethanesulfonic anhydride or trimethylsilyl triflate are reported. These show that following initial adduct formation with the promoter conversion of the 5-thioglucopyranosyl donors to the 5-thioglucopyranosyl triflates requires higher temperatures than that of the glucopyranosyl donors to the glucopyranosyl triflates. It is demonstrated that neighboring group participation is a less important phenomenon for the peracetylated thioglucosyl donors than for the peracetylated glucosyl donors. A simple thiocarbenium ion was generated by protonation of 2,3-dihydro-4H-thiopyran at low temperature and characterized by NMR spectroscopy. However, the corresponding 5-thioglucopyranosyl thenium ions were not observed in any of the NMR studies of the 5-thiopyranosyl donors: the electron-withdrawing C–O bonds around the thiopyranoside core discourage thiocarbenium ion formation, just as they discourage oxocarbenium ion formation. Density functional theory (DFT) calculations reveal the tetrahydrothiopyranyl thiocarbenium ion to be approximately 2.5 kcal/mol lower in energy than the corresponding tetrahydropyranyl oxocarbenium ion relative to the corresponding covalent triflates. However, the computations reveal a 5.8 kcal/mol activation barrier for conversion of the tetrahydrothiopyranyl triflate to the thiocarbenium ion, while formation of the oxocarbenium ion–triflate ion pair from tetrahydropyranyl triflate requires only 2.6 kcal·mol^–1. Overall, the greater axial selectivity of 5-thioglycopyranosyl donors compared to analogous glycopyranosyl donors derives from (i) the lower kinetic reactivity necessitating higher reaction temperatures, (ii) the greater stability of the thiocarbenium ion over the oxocarbenium ion facilitating equilibration under thermodynamic conditions, (iii) the greater magnitude of the anomeric effect in the 5-thiosugars, and (iv) decreased neighboring group participation in the per-esterified 5-thiosugars.

A primary explosive is a perfect chemical compound for starting ignition in military and commercial uses. Over the past century, the quest for lead-free, environmentally friendly primary explosives has been a significant challenge and a long-standing goal. Here, an innovative organic primary explosive, (E)-1,2-bis(3-azido-5-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)diazene (4), has been designed and synthesized through a straightforward three-step reaction from commercially available reagents. Importantly, this compound integrated two trifluoromethyl and azido groups into the N,N'-azo-1,2,4-triazole backbone to enhance the performance and safety. With this combination, it meets stringent criteria for safer, environmentally friendly primary explosives: being metal and perchlorate-free, possessing high density, excellent priming ability, and unique sensitivities to nonexplosive stimuli. It shows robust environmental resistance, good thermal stability, and effective detonation performance and also can be effectively initiated with a laser. Moreover, in the detonation test, compound 4 successfully detonated 500 mg of PETN with an ultralow minimum primer charge (MPC) of 40 mg, similar to traditional primary explosive LA (MPC: 40 mg) and outperforming organic metal-free primary explosives ICM-103 (MPC: 60 mg) and DDNP (MPC: 70 mg). The high detonation power, combined with its straightforward synthesis, cost-effectiveness, and easy large-scale manufacturing, makes it a superior alternative to currently used primary explosives such as lead azide (LA) and diazodinitrophenol (DDNP).