NMR Spectroscopic Signatures of Cationic Surface Sites from Supported Coinage Metals Interacting with N-Heterocyclic Carbenes.

N-heterocyclic carbenes (NHCs) have been extensively studied to modulate the reactivity of molecular catalysts, colloids, and their supported analogues, being isolated sites, clusters, or nanoparticles. While the interaction of NHCs on metal surfaces has been discussed in great detail, showing specific coordination chemistry depending on the type of NHC ligands, much less is known when the metal is dispersed on oxide supports, as in heterogeneous catalysts. Herein, we study the interaction of NHC ligands with Au surface sites dispersed on silica, a nonreducible oxide support. We identify the easy formation of bis-NHC ligated Au(I) surface sites parallel to what is found on metallic Au surfaces. These species display a specific 13C NMR spectroscopic signature that clearly distinguishes them from the mono-NHC Au(I) surface sites or supported imidazoliums. We find that bis-ligated surface species are not unique to supported Au(I) species and are found for the corresponding Ag(I) and Cu(I) species, as well as for the isolobal surface silanols. Furthermore, the interaction of NHC ligand with silica-supported Au nanoparticles also yields bis-NHC ligated Au(I) surface sites, indicating that metal atoms can also be easily extracted from nanoparticles, further illustrating the dynamics of these systems and the overall favorable formation of such bis-ligated species across a range of systems, besides what has been found on crystalline metal facets.

Isomerization of Aziridines to Allyl Amines via Titanium and Chromium Cooperative Catalysis.

A Ti/Cr cooperative catalyst isomerizes aziridines to allyl amines under mild conditions. The reaction tolerates a broad range of aziridines with various nitrogen substituents. The titanium catalyst is most successful in opening 1,2-disubstituted aziridines, forming radical intermediates in a highly regioselective manner. The chromium catalyst appears to abstract an H• from these radical intermediates and then return the H• to the titanium system in the form of an H+ and an electron. The reaction is complementary to previous reports on the isomerization of aziridines to allyl amines.

Direct and Indirect Electron Transfer Routes of Chromium(VI) Reduction with Different Crystalline Ferric Oxyhydroxides in the Presence of Pyrogenic Carbon.

Electron transfer mediated by iron minerals is considered as a critical redox step for the dynamics of pollutants in soil. Herein, we explored the reduction process of Cr(VI) with different crystalline ferric oxyhydroxides in the presence of pyrogenic carbon (biochar). Both low- and high-crystallinity ferric oxyhydroxides induced Cr(VI) immobilization mainly via the sorption process, with a limited reduction process. However, the Cr(VI) reduction immobilization was inspired by the copresence of biochar. Low-crystallinity ferric oxyhydroxide had an intense chemical combination with biochar and strong sorption for Cr(VI) via inner-sphere complexation, leading to the indirect electron transfer route for Cr(VI) reduction, that is, the electron first transferred from biochar to iron mineral through C-O-Fe binding and then to Cr(VI) with Fe(III)/Fe(II) transformation on ferric oxyhydroxides. With increasing crystallinity of ferric oxyhydroxides, the direct electron transfer between biochar and Cr(VI) became the main electron transfer avenue for Cr(VI) reduction. The indirect electron transfer was suppressed in the high-crystallinity ferric oxyhydroxides due to less sorption of Cr(VI), limited combination with biochar, and higher iron stability. This study demonstrates that electron transfer mechanisms involving iron minerals change with the mineral crystallization process, which would affect the geochemical process of contaminants with pyrogenic carbon.

Evolution of redox activity of biochar during interaction with soil minerals: Effect on the electron donating and mediating capacities for Cr(VI) reduction.

Biochar in soil is susceptible to natural aging along with soil minerals, which might alter its electrochemical properties and redox reactions with contaminants. In this study, soluble mineral salts (FeCl3, MnCl2, AlCl3, CaCl2) and clay mineral (kaolinite) were selected to investigate the impact of co-aging with soil minerals on the redox activity of peanut-shell biochar for Cr(VI) reduction. Natural aging for 3-month induced oxidation of biochar with the decrease of reducing moieties, i.e., ‒C‒OH from 26.8-43.7% to 18.4-24.1%. Co-aging with minerals except for Mn(II) further decreased the proportion of ‒C‒OH to 6.94-22.2% because of the interaction between mineral ions and biochar, resulting in the formation of mineral-biochar complex and new minerals, e.g. ß-FeOOH. Due to its reductivity, Mn(II) presented the least decrease or even slight increase of ‒C‒OH while itself was oxidized to Mn(III) and Mn(IV). The decline of ‒C‒OH caused the decrease of Cr(VI) reduction rate constant from 2.18 to 2.47 × 10-2 h-1 for original biochars to 0.71-1.95 × 10-2 h-1 for aged ones, of which co-aging with Fe(III) showed the lowest reduction rate constant among all minerals. The electron mediating capacity of biochar also decreased after aging alone or co-aging with Al, Ca, and kaolinite, while co-aging with Fe(III) and Mn(II) facilitated the electron transfer process, increasing the rate constant by 219.3-1237% due to electron mediation through valence transformation of Fe(III)-Fe(II) and Mn(II)-Mn(III). Given the abundance of soil minerals, it was essential to consider this crucial factor for redox reactions when applying biochar for soil remediation.

Catalyzing the Hydrodefluorination of CF3-Substituted Alkenes by PhSiH3. H• Transfer from a Nickel Hydride.

The hydrodefluorination of CF3-substituted alkenes can be catalyzed by a nickel(II) hydride bearing a pincer ligand. The catalyst loading can be as low as 1 mol%. gem-Difluoroalkenes containing a number of functional groups can be formed in good to excellent yields by a radical mechanism initiated by H• transfer from the nickel hydride. The relative reactivity of various substrates supports the proposed mechanism, as does a TEMPO trapping experiment.

Interaction with low molecular weight organic acids affects the electron shuttling of biochar for Cr(VI) reduction.

Biochar can act as "electron shuttle" in soil redox reactions. It is possible that biochar accepts the electrons from low molecular weight organic acids (LMWOAs) in soil and then transfer them to the acceptors, e.g., Cr(VI). This study evaluated the interaction between seven soil LMWOAs and peanut shell biochar (BC) as well as its effect on the electron shuttling of biochar for Cr(VI) reduction. Both redox reactions and sorption process occurred during the interaction of biochar and LMWOAs, which altered the contents of Cr(VI) reduction-relevant groups (i.e., CO and CO) on the surface of biochar. The redox reactions were more important to the electron transfer between biochar produced at 400℃ (BC400) and LMWOAs due to the repeated cycle of reduction-oxidation of surface functional groups. The reduction rate of Cr(VI) by LMWOAs mediated by BC400 was 1.10-7.09 × 10-3 h-1, among which tartaric acid had the best reduction efficiency due to its highest reducing capability. For biochar produced at 700℃ (BC700), the sorption process of LMWOAs was the key factor to the direct electron shuttling process through the conjugated structure of biochar. The reduction rate of Cr(VI) by LMWOAs mediated by BC700 was significantly higher and ranged 7.40-864 × 10-3 h-1, with the oxalic acid having the best reduction efficiency due to its highest sorption capacity by BC700. The results obtained from this study can help to establish the linkage between biochar and LMWOAs in soil electron network, which better explains the multifunctional roles of biochar during the redox processes such as Cr(VI) reduction in soil.

Anti-Markovnikov alcohols via epoxide hydrogenation through cooperative catalysis.

The opening of epoxides typically requires electrophilic activation, and subsequent nucleophilic (SN2) attack on the less substituted carbon leads to alcohols with Markovnikov regioselectivity. We describe a cooperative catalysis approach to anti-Markovnikov alcohols by combining titanocene-catalyzed epoxide opening with chromium-catalyzed hydrogen activation and radical reduction. The titanocene enforces the anti-Markovnikov regioselectivity by forming the more highly substituted radical. The chromium catalyst sequentially transfers a hydrogen atom, proton, and electron from molecular hydrogen, avoiding a hydride transfer to the undesired site and resulting in 100% atom economy. Each step of the interconnected catalytic cycles was confirmed separately.

H· Transfer-Initiated Synthesis of γ-Lactams: Interpretation of Cycloisomerization and Hydrogenation Ratios.

A cobaloxime/H2 system used to synthesize valuable γ-lactams from acrylamide molecules is described. In addition to cycloisomerized lactams, linear hydrogenated products were also observed. The amounts of the hydrogenation product were observed to correlate with the bulk of the substituent on the acrylamide nitrogen. Further analysis of the product distributions with experimental and computational studies suggested that while cyclization can occur from one C=C acrylamide rotamer, hydrogenation can occur from both. This observation was further evinced through calculation of the hydrogenation rate constant, which was observed to be ca. 102 faster than previously determined for a related system using n Bu3SnH.

Small Molecule and Peptide Recognition of Protein Transmembrane Domains.

Membrane proteins play vital roles in cell signaling, molecular transportation, and cell adhesion. The interactions of transmembrane domains are much less well understood than those of their water-soluble counterparts, and they have been deemed "undruggable" despite their important biological functions such as protein anchoring, signal transduction, and ligand recognition. Nevertheless, continual developments in this area have revealed useful probes for investigating and regulating these membrane proteins. This review summarizes and evaluates the strategies available for discovering small molecules and peptides that recognize the protein transmembrane domains of membrane proteins, with a particular focus on rational design and library screening.

Pyrimidine Triazole Thioether Derivatives as Toll-Like Receptor†5 (TLR5)/Flagellin Complex Inhibitors.

Protein-protein interactions have been regarded as "undruggable" despite their importance in many biological processes. The complex formed between host toll-like receptor 5 (TLR5) and flagellin, a globular protein that is the main component of a bacterial flagellum, plays a vital role in a number of pathogen defenses, immunological diseases and cancers. Through high-throughput screening, we identified two hits with a common pharmacophore, which were used to successfully develop a series of small-molecule probes as novel inhibitors of flagellin binding to TLR5. In a multitude of assays, 4-((4-benzyl-5-(pyridin4yl)-4H-1,2,4-triazol-3-yl)thio)pyrido[3',2':4,5]thieno[3,2-d]pyrimidine (TH1020) was identified as a potent antagonist of TLR5 signaling with promising activity (IC50 =0.85±0.12 µm) and specificity. Furthermore, TH1020 was shown to repress the expression of downstream TNF-α signaling pathways mediated by the TLR5/flagellin complex formation. Based on molecular docking simulation, TH1020 is suggested to compete with flagellin and disrupt its association with TLR5. TH1020 provides a much-needed molecular probe for studying this important protein-protein interaction and a lead compound for identifying novel therapeutics targeting TLR5.