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Understanding the structure of Ru(V)-oxo species is crucial for designing novel catalysts for sustainable energy applications, such as water splitting for green hydrogen production. This study reports the EPR detection of a Ru(V)-oxo intermediate stabilized by terpyridine and phenanthroline carboxylate ligands. The interaction between the carboxylate group and the ruthenium center, along with PCET-dependent hemilability under oxidative conditions, plays a critical role in achieving the high-valent state. Subtle changes in the coordination environment around the central metal also proved to be essential. Low-temperature NMR, high-resolution mass spectrometry, UV–Vis spectroscopy, and density functional theory calculations support these findings.

Herein, we report a mild and efficient cobalt-catalyzed electrochemical method for the regioselective C–H acyloxylation of aromatic and vinylic amides, utilizing 8-aminoquinoline as the directing group. Notably, this protocol requires no stoichiometric oxidants and operates at room temperature in an undivided cell setup, providing sustainable access to a diverse set of ortho-acyloxylated products with broad functional group tolerance.

Chloroarenes constitute fundamental building blocks in organic synthesis and are widely applied in the synthesis of bioactive compounds, fine chemicals, materials, natural products and pharmaceuticals. Electrochemical chlorination has been recognized as a promising synthetic method for accessing chloroarenes, but it has proved challenging to achieve in practice as shown by the limited number of existing protocols. Herein, we report on a highly general electrocatalytic strategy for the regioselective chlorination of various substituted heteroaryl scaffolds in an undivided cell setup, using ethyl chloroformate as the chlorine source. This strategy offers several practical advantages over existing methodologies, including an operationally simple experimental setup, exceptional functional group tolerance, and the possibility to form either the mono- or bis-chlorinated products in high selectivity depending on the choice of catalyst loading, electric current and ethyl chloroformate equivalents. The practicality and selectivity of the protocol were demonstrated by the successful chlorination of an array of densely-substituted arene frameworks as well as by the synthesis of chlorinated bioactive molecules.

Green hydrogen production from water is one attractive route to non-fossil fuel and a potential source of clean energy. Hydrogen is not only a zero-carbon energy source but can also be utilized as an efficient storage of electrical energy generated through various other sources, such as wind and solar. Cost-effective and environmentally benign direct hydrogen production through neutral water (similar to pH 7) reduction is particularly challenging due to the low concentration of protons. There is currently a major need for easy-to-prepare, robust, as well as active electrode materials. Herein we report three new molecular electrodes that were prepared by anchoring commercially available, and environmentally benign cobalt-containing electrocatalysts with three different ligand frameworks (porphyrin, phthalocyanine, and corrin) on a structurally modified graphite foil surface. Under the studied reaction conditions (over 7 h at 22 degrees C), the electrode with Co-porphyrin is the most efficient for the water reduction with starting similar to 740 mV onset potential (OP) (vs. RHE, current density 2.5 mA/cm(2)) and a Tafel slope (TS) of 103 mV/dec. It is followed by the molecular electrodes having Co-phthalocyanine [825 mV (OP), 138 mV/dec (TS)] and Vitamin-B-12 (Co-corrin moiety) [830 mV (OP), 194 mv/dec (TS)]. A clear time-dependent improvement (>200 mV over 3 h) in the H-2 production overpotential with the Co-porphyrin-containing cathode was observed. This is attributed to the activation due to water coordination to the Co-center. A long-term chronopotentiometric stability test shows a steady production of hydrogen from all three cathode surfaces throughout seven hours, confirmed using an H(2 )needle sensor. At a current density of 10 mA/cm(2), the Co-porphyrin-containing electrode showed a TOF value of 0.45 s(-1) at 870 mV vs. RHE, whereas the Co-phthalocyanine and Vitamin-B-12-containing electrodes showed 0.37 and 0.4 s(-1) at 1.22 V and 1.15 V (vs. RHE), respectively.

In vitro screening of large compound libraries with automated high-throughput screening is expensive and time-consuming and requires dedicated infrastructures. Conversely, the selection of DNA-encoded chemical libraries (DECLs) can be rapidly performed with routine equipment available in most laboratories. In this study, we identified novel inhibitors of SARS-CoV-2 main protease (M^pro) through the affinity-based selection of the DELopen library (open access for academics), containing 4.2 billion compounds. The identified inhibitors were peptide-like compounds containing an N-terminal electrophilic group able to form a covalent bond with the nucleophilic Cys145 of M^pro, as confirmed by x-ray crystallography. This DECL selection campaign enabled the discovery of the unoptimized compound SLL11 (IC₅₀ = 30 nM), proving that the rapid exploration of large chemical spaces enabled by DECL technology allows for the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. As demonstrated further by x-ray crystallography, SLL11 was found to adopt a highly unique U-shaped binding conformation, which allows the N-terminal electrophilic group to loop back to the S1′ subsite while the C-terminal amino acid sits in the S1 subsite. MP1, a close analog of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC₅₀ = 2.3 µM) cell lines. As peptide-like compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds will be explored in the future to improve their antiviral activity.

The instability of molecular electrodes under oxidative/reductive conditions and insufficient understanding of the metal oxide-based systems have slowed down the progress of H-2-based fuels. Efficient regeneration of the electrode's performance after prolonged use is another bottleneck of this research. This work represents the first example of a bifunctional and electrochemically regenerable molecular electrode which can be used for the unperturbed production of H-2 from water. Pyridyl linkers with flexible arms (-CH2-CH2-) on modified fluorine-doped carbon cloth (FCC) were used to anchor a highly active ruthenium electrocatalyst [Ru-II(mcbp)(H2O)(2)] (1) [mcbp(2-) = 2,6-bis(1-methyl-4-(carboxylate)benzimidazol-2-yl)pyridine]. The pyridine unit of the linker replaces one of the water molecules of 1, which resulted in RuPFCC (ruthenium electrocatalyst anchored on -CH2-CH2-pyridine modified FCC), a high-performing electrode for oxygen evolution reaction [OER, overpotential of similar to 215 mV] as well as hydrogen evolution reaction (HER, overpotential of similar to 330 mV) at pH 7. A current density of similar to 8 mA cm(-2) at 2.06 V (vs. RHE) and similar to-6 mA cm(-2) at -0.84 V (vs. RHE) with only 0.04 wt% loading of ruthenium was obtained. OER turnover of >7.4 x 10(3) at 1.81 V in 48 h and HER turnover of >3.6 x 10(3) at -0.79 V in 3 h were calculated. The activity of the OER anode after 48 h use could be electrochemically regenerated to similar to 98% of its original activity while it serves as a HE cathode (evolving hydrogen) for 8 h. This electrode design can also be used for developing ultra-stable molecular electrodes with exciting electrochemical regeneration features, for other proton-dependent electrochemical processes.

The low stability of the electrocatalysts at water oxidation (WO) conditions and the use of expensive noble metals have obstructed large-scale H-2 production from water. Herein, we report the electrocatalytic WO activity of a cobalt-containing, water-soluble molecular WO electrocatalyst [Co-II(mcbp)(OH2)] (1) [mcbp(2-)=2,6-bis(1-methyl-4-(carboxylate)benzimidazol-2-yl)pyridine] in homogeneous conditions (overpotential of 510 mV at pH 7 phosphate buffer) and after anchoring it on pyridine-modified fluorine-doped carbon cloth (PFCC). The formation of cobalt phosphate was identified only after 4 h continuous oxygen evolution in homogeneous conditions. Interestingly, a significant enhancement of the stability and WO activity (current density of 5.4 mA/cm(2) at 1.75 V) was observed for 1 after anchoring onto PFCC, resulting in a turnover (TO) of >3.6x10(3) and average TOF of 0.05 s(-1) at 1.55 V (pH 7) over 20 h. A total TO of >21x10(3) over 8 days was calculated. The electrode allowed regeneration of similar to 85 % of the WO activity electrochemically after 36 h of continuous oxygen evolution.

Herein, we report an electrochemical oxidative palladium-catalyzed carbonylation-carbocyclization of enallenols to afford γ-lactones and spirolactones, which proceeds with excellent chemoselectivity. Interestingly, electrocatalysis was found to have an accelerating effect on the rate of the tandem process, leading to a more efficient reaction than that under chemical redox conditions.

This work outlines a synthetic route that can be used to access chiral cyclobutane keto acids with two stereocenters in five steps from the inexpensive terpene myrtenal. Furthermore, the developed route includes an 8-aminoquinoline- directed C(sp(2))-H arylation as one of its key steps, which allows a wide range of aryl and heteroaryl groups to be incorporated into the bicyclic myrtenal scaffold prior to the ozonolysis-based ringo-pening step that furnishes the target cyclobutane keto acids. This synthetic route is expected to find many applications connected to the synthesis of natural product-like compounds and small molecule libraries.

A well-studied heterogeneous palladium(II) catalyst used for the cycloisomerization of acetylenic acids is known to be susceptible to deactivation through reduction. To gain a deeper understanding of this deactivation process and to enable the design of a reactivation strategy, in situ X-ray absorption spectroscopy (XAS) was used. With this technique, changes in the palladium oxidation state and coordination environment could be studied in close detail, which provided experimental evidence that the deactivation was primarily caused by triethylamine-promoted reduction of palladium(II) to metallic palladium nanoparticles. Furthermore, it was observed that the choice of the acetylenic acid substrate influenced the distribution between palladium(II) and palladium(0) species in the heterogeneous catalyst after the reaction. From the mechanistic insight gained through XAS, an improved catalytic protocol was developed that did not suffer from deactivation and allowed for more efficient recycling of the catalyst.