The catalytic hydrogenation of carbon dioxide and bicarbonate to formate has been explored extensively. The vast majority of the known active catalyst systems are based on precious metals. Herein, we describe an effective, phosphine-free, air- and moisture-tolerant catalyst system based on Knölker’s iron complex for the hydrogenation of bicarbonate and carbon dioxide to formate. The catalyst system can hydrogenate bicarbonate at remarkably low hydrogen pressures (1–5 bar).

Antimycin and cyazofamid are specific inhibitors of the mitochondrial respiratory chain and bind to the Q_i site of the cytochrome bc₁ complex. With the aim to understand the detailed molecular inhibition mechanism of Q_i inhibitors, we performed a comparative investigation of the inhibitory kinetics of them against the porcine bc₁ complex. The results showed that antimycin is a slow tight-binding inhibitor of succinate–cytochrome c reductase (SCR) with K_i = 0.033 ± 0.00027 nm and non-competitive inhibition with respect to cytochrome c. Cyazofamid is a classical inhibitor of SCR with K_i = 12.90 ± 0.91 μm and a non-competitive inhibitor with respect to cytochrome c. Both of them show competitive inhibition with respect to substrate DBH₂. Further molecular docking and quantum mechanics calculations were performed. The results showed that antimycin underwent significant conformational change upon the binding. The energy barrier between the conformations in the crystal and in the binding pocket is ~13.63 kcal/mol. Antimycin formed an H-bond with Asp228 and two water-bridged H-bonds with Lys227 and His201, whereas cyazofamid formed only one H-bond with Asp228. The conformational change and the different hydrogen bonding network might account for why antimycin is a slow tight-binding inhibitor, whereas cyazofamid is a classic inhibitor.

Protoporphyrinogen oxidase (EC 1.3.3.4) is one of the most significant targets for a large family of herbicides. As part of our continuous efforts to search for novel protoporphyrinogen oxidase-inhibiting herbicides, N-(benzothiazol-5-yl)tetrahydroisoindole-1,3-dione was selected as a lead compound for structural optimization, leading to the syntheses of a series of novel N-(benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones (1a–o) and N-(benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones (2a–i). These newly prepared compounds were characterized by elemental analyses, ¹H NMR, and ESI-MS, and the structures of 1h and 2h were further confirmed by X-ray diffraction analyses. The bioassays indicated that some compounds displayed comparable or higher protoporphyrinogen oxidase inhibition activities in comparison with the commercial control. Very promising, compound 2a, ethyl 2-((6-fluoro-5-(4,5,6,7-tetrahydro-1-oxo-1H-isoindol-2(3H)-yl)benzo[d]thiazol-2-yl)-sulfanyl)acetate, was recognized as the most potent candidate with K_i value of 0.0091 μm. Further greenhouse screening results demonstrated that some compounds exhibited good herbicidal activity against Chenopodium album at the dosage of 150 g/ha.

Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1), also known as mitochondrial respiratory complex II or succinate dehydrogenase (SDH), catalyzes the oxidation of succinate to fumarate as part of the tricarboxylic acid cycle. SQR has been identified as a novel target of a large family of agricultural fungicides. However, the detailed mechanism of action between the fungicides and SQR is still unclear, and the bioactive conformation of fungicides in the SQR binding pocket has not been identified. In this study, the kinetics of porcine SQR inhibition by ten commercial carboxamide fungicides were measured, and noncompetitive inhibition was observed with respect to succinate, DCIP, and cytochrome c, while competitive inhibition was observed with respect to ubiquinone. With the aim to uncover the binding conformation of these fungicides, molecular docking, molecular dynamics simulation, and molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations were then performed. The excellent correlation (r²=0.94) between the calculated (ΔG_cal) and experimental (ΔG_exp) binding free energies indicates that the obtained docking conformation could be the bioactive conformation. The acid moiety of carboxamide fungicides inserts into the ubiquinone binding site (Q-site) of SQR, forming van der Waals (vdW) interactions with C_R46, C_S42, B_I218, and B_P169, while the amine moiety extends to the mouth of the Q-site, forming vdW interactions with C_W35, C_I43, and C_I30. The carbonyl oxygen atom of the carboxamide forms hydrogen bonds with B_W173 and D_Y91. These findings provide valuable information for the design of more potent and specific inhibitors of SQR.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is one of the most significant targets for a large family of inhibitors that may be used as herbicide, bactericide, fungicide, or photosensitizing activator to treat cancer through photodynamic therapy (PDT). Molecular docking and CoMFA were combined in a multistep framework with the ultimate goal of identifying important factor contributing to the activity of PPO inhibitors. As a continuation of the previous research work on the development of new PPO inhibitors, the bioassay results indicated that good PPO inhibitors were discovered in all of the three chemical series with IC₅₀ values ranging from 0.010 to 0.061 µmol·L⁻¹. Using the crystal structure of tobacco mitochondrial PPO (mtPPO) as template, all the compounds were docked into the enzyme active site. The docking pose of each compound was subsequently used in a receptor-based alignment, leading to the development of a significant CoMFA model with r² value of 0.98 and q² (cross validation r²) value of 0.63. This novel multistep framework gives insight into the structural characteristics for the binding of inhibitors, and it can be extended to other classes of PPO inhibitors. In addition, the simplicity of the proposed approach may be particularly applicable in virtual screening procedures.

Strobilurins are one of the most important natural products with fungicidal activities and well known for their novel action mode, broad fungicidal spectrum, lower toxicity against mammalian cells, and environmentally benign characteristics. Design and syntheses of strobilurin analogues therefore have attracted great attention in the field of agrochemistry. Previously, we successfully developed a new molecular design method of pharmacophore-linked fragment virtual screening (PFVS) and discovered a lead compound (E)-methyl-2-(2-(((3-(imino-(phenyl)methyl)phenyl)thio)methyl)phenyl)-3-methoxyacrylate (1). To discover new strobilurin analogues with higher fungicidal activity, the structural modification of compound 1 was carried out guided by bioisosterism. A series of benzophenone derivatives 2a–2j were synthesized, among which compound 2j with a K_i value of 1.89 nmol/L was identified as the most promising inhibitor of porcine cytochrome bc₁ complex, 157-fold improved binding affinity compared to the commercially available bc₁ inhibitor Azoxystrobin (AZ). In addition, most of the new compounds displayed excellent fungicidal activity against Sphaerotheca fuliginea at the concentration of 200 µmol/L. The present work indicates that strobilurin analogues containing benzophenone side chains may be the ideal leads for future fungicide discovery.

A novel three-component reaction of o-bromobenzaldehyde, terminal alkynes and tert-butyl amine has been established, which proceeded smoothly to give 3-substituted isoquinolines in good yields in the presence of palladium/copper catalysts under microwave irradiation.

The cytochrome bc₁ complex (complex III, cyt bc₁) is an essential component of cellular respiration. Cyt bc₁ has three core subunits that are required for its catalytic activity: cytochrome b, cytochrome c₁, and the Rieske iron–sulfur protein (ISP). Although most fungicides inhibit this enzyme by binding to the cytochrome b subunit, resistance to these fungicides has developed rapidly due to their widespread application. Resistance is mainly associated with mutations in cytochrome b, the only subunit encoded by mitochondrial DNA. Recently, the flexibility and motion of the ISP and its essential role in electron transfer have received intense attention; this leads us to propose a new classification of cyt bc₁ inhibitors (three types of Q_o inhibitors) that mobilize, restrict, or fix the rotation of the ISP. Importantly, the strengths of the ISP–inhibitor interactions correlate with inhibitor activity and the development of resistance to Q_o inhibitors, thereby offering clues for designing novel cyt bc₁ inhibitors with high potency and a low risk of resistance.

A series of new acetohydrazone-containing 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized for the purpose of searching for novel agrochemicals with higher fungicidal activity. Their in vitro fungicidal activities against Rhizoctonia solani were evaluated, and the most promising compound, 2-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)sulfanyl]-2′-[(2-hydroxyphenyl)methylidene]acetohydrazide (2-17), showed a lower EC₅₀ value (5.34 μg ml⁻¹) than that of commercial carbendazim (EC₅₀=7.62 μg ml⁻¹). Additionally, compound 2-17 was also found to display broad-spectrum fungicidal activities, and its EC₅₀ value (4.56 μg ml⁻¹) against Botrytis cinereapers was very similar to that of carbendazim. Qualitative structure–activity relationships (QSARs) of the synthesized compounds were also discussed.