ACS Combinatorial Science最新文献

Nucleoside analogues have seen significant advancements in treating viral infections and cancer through ProTide technology, leading to a series of FDA-approved drugs such as sofosbuvir, tenofovir alafenamide, and remdesivir. The stereochemical configuration at the phosphorus center of ProTides significantly influences their pharmacological properties, necessitating efficient stereoselective synthesis. Traditional methods using chiral auxiliaries or nonracemic phosphorylating agents are labor-intensive and inefficient, while recent organocatalytic approaches, despite their promise, still face limitations. Herein, we present a novel approach employing chiral metal complexes for the stereoselective assembly of P-stereogenic ProTides via asymmetric P–O bond formation. This approach leverages a chiral metal catalyst to activate the electrophilic phosphorylating reagent, facilitating a base-promoted nucleophilic replacement pathway. Our protocol, featuring mild reaction conditions and broad applicability, enables the highly stereoselective synthesis of previously inaccessible (S,R_P) and (R,S_P)-ProTide derivatives. The practical utility of this method is demonstrated through the preparation of pharmaceutically relevant ProTide targets and mechanistic studies were conducted to elucidate the reaction pathway, offering significant advancements for drug development and pharmaceutical research.

Aziridines are the smallest nitrogen-containing heterocycles. Strain-enhanced electrophilicity renders aziridines useful synthetic intermediates and gives rise to biological activity. Classical aziridine syntheses─based on either [2 + 1] cycloadditions or intramolecular substitution chemistry─assemble aziridines from acyclic precursors. Here, we introduce N-aziridinyl radicals as a reactive intermediate that enables the transfer of intact aziridine fragments in organic synthesis. Transient N-aziridinyl radicals are generated by the reductive activation of N-pyridinium aziridines and are directly characterized by spin-trapped EPR spectroscopy. In the presence of O₂, N-aziridinyl radicals are added to styrenyl olefins to afford 1,2-hydroxyaziridination products. These results establish aziridinyl radicals as new reactive intermediates in synthetic chemistry and demonstrate aziridine group transfer as a viable synthetic disconnection.

The generation of difluorocarbene from difluoromethane bis(sulfonium ylide) 1 through spin-forbidden excitation under irradiation with 450 nm blue light was reported. The formation of difluorocarbene was confirmed by its reaction with styrene derivatives for the generation of difluorocyclopropanation and insertion into RX–H bonds (X = O, S) for the generation of RXCF₂H. The spin-forbidden excitation mechanism for the formation of difluorocarbene from difluoromethane bis(sulfonium ylide) was supported by spectroscopic and kinetic studies as well as computational chemistry. The homolytic cleavage of two S–C bonds in compound 1 under irradiation was confirmed by time-resolved EPR spectroscopic studies of the precursor’s free-radical-capturing reaction, as well as the isolation of the dimer of dimethyl (phenylthiol)malonyl radical. Further studies showed that the homolytic cleavage process occurred asynchronously in the solvent cage based on the isotope-labeled scrambling experiments and DFT calculations.

The electrochemical oxidation of ammonia (NH₃) enables decentralized small-scale synthesis of nitrate (NO₃^–) and nitrite (NO₂^–) under ambient conditions by directly utilizing renewable energy. Yet, their electrosynthesis has been restricted to aqueous media and low ammonia concentrations. For the first time, we demonstrate here a strategy enabling the direct electrooxidation of liquefied NH₃ to NO₃^– and NO₂^– by using molecular oxygen, achieving combined Faraday efficiencies above 40%.

The primary cause of the accelerated battery failure in aqueous zinc-ion batteries (AZIBs) is the uncontrollable evolution of the zinc metal–electrolyte interface. In the present research on the development of multiadditives to ameliorate interfaces, it is challenging to elucidate the mechanisms of the various components. Additionally, the synergy among additive molecules is frequently disregarded, resulting in the combined efficacy of multiadditives that is unlikely to surpass the sum of each component. In this study, the “molecular synergistic effect” is employed, which is generated by two nonhomologous acid ester (NAE) additives in the double electrical layer microspace. Specifically, ethyl methyl carbonate (EMC) is more inclined to induce the oriented deposition of zinc metal by means of targeted adsorption with the zinc (002) crystal plane. Methyl acetate (MA) is more likely to enter the solvated shell of Zn²⁺ and will be profoundly reduced to produce SEI that is dominated by organic components under the “molecular synergistic effect” of EMC. Furthermore, MA persists in a spontaneous hydrolysis reaction, which serves to mitigate the pH increase caused by the hydrogen evolution reaction (HER) and further prevents the formation of byproducts. Consequently, the 1E1M electrolyte not only extends the cycle life of the zinc anode to 3140 cycles (1 mA h cm^–2 and 1 mA cm^–2) but also extends the life of the Zn//MnO₂ full battery, with the capacity retention rate still at 89.9% after 700 cycles.

Electrosynthesis of H₂O₂ provides an environmentally friendly alternative to the traditional anthraquinone method employed in industry, but suffers from impurities and restricted yield rate and concentration of H₂O₂. Herein, we demonstrated a Ni-phthalocyanine-based covalent-organic framework (COF, denoted as BBL-PcNi) with a higher inherent conductivity of 1.14 × 10^–5 S m^–1, which exhibited an ultrahigh current density of 530 mA cm^–2 with a Faradaic efficiency (H₂O₂) of ∼100% at a low cell voltage of 3.5 V. Notably, this high level of performance is maintained over a continuous operation of 200 h without noticeable degradation. When integrated into a scale-up membrane electrode assembly electrolyzer and operated at ∼3300 mA at a very low cell voltage of 2 V, BBL-PcNi continuously yielded a pure H₂O₂ solution with medical-grade concentration (3.5 wt %), which is at least 3.5 times higher than previously reported catalysts and 1.5 times the output of the traditional anthraquinone process. A mechanistic study revealed that enhancing the π-conjugation to reduce the band gap of the molecular catalytic sites integrated into a COF is more effective to enhance its inherent electron transport ability, thereby significantly improving the electrocatalytic performance for H₂O₂ generation.

There is no report on the (anti)aromaticity of metallacyclopentatrienes, one kind of common and important five-membered metallacycles. This work presents the novel synthesis of osmium cis-biscarbene complexes and their oxidation to osmacyclopentatrienes. The osmacyclopentatriene unit is antiaromatic, as revealed by experimental and theoretical studies. This finding provides new insight into the discovery of antiaromatic species.

Molecular chains of two-coordinate carbon atoms (cumulenes) have long been targeted, due to interest in the electronic structure and applications of extended π-systems, and their relationship to the carbon allotrope, carbyne. While formal (isoelectronic) B═N for C═C substitution has been employed in two-dimensional (2-D) materials, unsaturated one-dimensional all-inorganic “molecular wires” are unknown. Here, we report high-yielding synthetic approaches to heterocumulenes containing a five-atom BNBNB chain, the geometric structure of which can be modified by choice of end group. The diamido-capped system is bent at the 2-/4-positions, and natural resonance theory calculations reveal significant contributions from B═N(:)–B≡N–B resonance forms featuring a lone pair at N (consistent with observed N-centered nucleophilicity). Molecular modification to generate a linear system best described by a B═N═B═N═B resonance structure involves chemical transformation of the capping groups (using B(C₅F₅)₃) to enhance their π-acidity and conjugate the N-lone pairs.

A key feature of coordination cages is the dynamic nature of their coordinative bonds, which facilitates the synthesis of complex polyhedral structures and their post-assembly modification. However, this dynamic nature can limit cage stability. Increasing cage robustness is important for real-world use cases. Here we introduce a double-bridging strategy to increase cage stability, where designed pairs of bifunctional subcomponents combine to generate rectangular tetratopic ligands within pseudo-cubic Zn₈L₆ cages. These cages withstand transmetalation, the addition of competing ligands, and nucleophilic imines, under conditions where their single-bridged congeners decompose. Our approach not only increases the stability and robustness of the cages while maintaining their polyhedral structure, but also enables the incorporation of additional functional units in proximity to the cavity. The double-bridging strategy also facilitates the synthesis of larger cages, which are inaccessible as single-bridged congeners.

The unique ionic channels and highly polar pore structures have distinguished crystalline porous organic salts (CPOSs) from conventional porous frameworks in the past decade. Up to now, CPOSs were all constructed by a monoionic strategy, in which two types of building units individually bearing anionic or cationic groups were introduced, thus increasing complexity in the synthesis of CPOSs. In this study, by utilizing stereoisomeric compounds of TPE-NS-Z or TPE-NS-E bearing both anionic and cationic groups as a single building unit, the zwitterionic strategy was proven feasible in constructing CPOSs. Benefiting from the single building unit, the zwitterionic strategy simplified the preparation process and reduced the difficulty in studying the aggregation behavior of building units into CPOSs. And also, this novel strategy enabled precise control of the finally obtained CPOSs through fine-tuning of the initial building units. Surprisingly, the special parallel/vertical alternated stacking mode and unique ionic interaction networks in the crystal structure provided the flexible pore characteristic of CPOS-E, which further guaranteed the multitime controllable release of highly polar chemicals in different solvents.