Photoredox Reactions and the Catalytic Cycle for Carbon Dioxide Fixation and Methanogenesis on Metal Oxides

Photoirradiated metal oxide semiconductors are known to reduce carbon dioxide to methane. This multistep reaction is commonly represented as a sequence of proton-coupled two-electron reactions leading from carbon dioxide to formate to formaldehyde to methanol and to methane. We suggest that the actual reaction mechanism is more complex, as it involves two-carbon molecules and radicals in addition to these one-carbon species. The ″stepping stone″ of this mechanism for carbon dioxide fixation could be glyoxal, which is the product of recombination of two formyl radicals, or glycolaldehyde, which is its reduced form. We demonstrate the main steps of this reduction chain and suggest a catalytic cycle integrating these steps and the radical chemistry. In addition to methane, this cycle generates complex organic molecules, such as glycolaldehyde, acetaldehyde, and methylformate, which were observed in product analyses. This cycle can be regarded as one of the simplest realizations of multistep, photosynthetic fixation of atmospheric carbon in prebiotic nature

Nature of Interaction between Semiconducting Nanostructures and Biomolecules: Chalcogenide QDs and BNNT with DNA Molecules

Interactions of DNA oligomers with two categories of semiconducting nanostructureschalcogenide quantum dots (QDs) and boron nitride nanotubes (BNNTs)owing to their widespread presence in bio-inspired processes are investigated using the first-principles density functional theory and continuum solvent model. The chalcogenide QDs interact strongly at their metal centers featuring electrostatic interaction with DNA oligomers at oxygen or nitrogen site, while BNNTs form covalent bonds with DNA oligomers at multiple surface sites. It is found that the different bonding nature leads to distinctly different response to the aqueous environment; the presence of solvent drastically reduces the binding strength of nucleobases with the QDs due to the strong electrostatic screening. This is not the case with BNNTs for which the covalent bonding is barely affected by the solvent. This study thus clearly shows how a solvent medium influences chemical interactions providing guidance for technological applications of bioconjugated systems

Heteroatom-Transfer Coupled Photoreduction and Carbon Dioxide Fixation on Metal Oxides

Photoactive metal oxides, such as hydrated TiO₂, are known to reduce carbon dioxide to methane, but the mechanism for this photoreaction is insufficiently understood. In particular, it is not known whether the reduction of crucial reaction intermediates, including the formate anion, involves one- or two-electron reactions. In this study, we demonstrate that formic acid and its derivatives can be reduced to the formyl radical via a concerted reaction in which the electron transfer is coupled to oxygen transfer to a Ti³⁺ center on the oxide surface. Several other examples of such heteroatom-transfer reactions are demonstrated, suggesting a general pattern. The implications of these reactions for photocatalytic methanogenesis, perchlorate diagenesis, and planetary chemistry on Mars are discussed

Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2‑<i>c</i>]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment

The discovery of novel tetrahydropyrrolo­[1,2-<i>c</i>]­pyrimidines derivatives from <b>Bay41_4109</b> as hepatitis B virus (HBV) inhibitors is herein reported. The structure–activity relationship optimization led to one highly efficacious compound <b>28a</b> (IC₅₀ = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of <b>28a</b> against HBV replication

Discovery of 3,3′-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection

A new series of 3,3′-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure–activity relationship study led to a lead compound <b>14h</b>, which exhibited excellent <i>in vitro</i> potency with an EC₅₀ value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, <b>14h</b> demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg

Discovery of Potent EV71 Capsid Inhibitors for Treatment of HFMD

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. The viral caspid protein VP1 is a well-known target for antiviral efficacy because its occupancy by suitable compounds could stabilize the virus capsid, thus preventing uncoating of virus for RNA release. In this Letter, design, synthesis, and biological evaluation of novel anti-EV71 agents (aminopyridyl 1,2,5-thiadiazolidine 1,1-dioxides) are described. One of the most promising compounds (<b>14</b>) showed excellent antiviral activity against EV71 (EC₅₀ = 4 nM) and exhibited excellent <i>in vivo</i> efficacy in the EV71 infected mouse model

Synthesis and Biological Evaluation of a Series of Bile Acid Derivatives as FXR Agonists for Treatment of NASH

Farnesoid X receptor (FXR) has become a particularly attractive target for the discovery of drugs for the treatment of liver and metabolic diseases. Obeticholic acid (<b>INT-747</b>), a FXR agonist, has advanced into clinical phase III trials in patients with nonalcoholic steatohepatitis (NASH), but adverse effects (e.g., pruritus, LDL increase) were observed. Pruritus might be induced by Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1), and there are chances to develop FXR agonists with higher selectivity over TGR5. In this letter, novel bile acids bearing different modifications on ring A and side chain of <b>INT-747</b> are reported and discussed. Our results indicated that the side chain of <b>INT-747</b> is amenable to a variety of chemical modifications with good FXR potency <i>in vitro</i>. Especially, compound <b>18</b> not only showed promising FXR potency and excellent pharmacokinetic properties, but also proved superior pharmacological efficacy in the HFD + CCl₄ model