Voltage-Gated Electrocatalysis of Efficient and Selective Methane Oxidation by Tricopper Clusters under Ambient Conditions.

Selective methane oxidation is difficult chemistry. Here we describe a strategy for the electrocatalysis of selective methane oxidation by immobilizing tricopper catalysts on the cathodic surface. In the presence of dioxygen and methane, the activation of these catalysts above a threshold cathodic potential can initiate the dioxygen chemistry for O atom transfer to methane. The catalytic turnover is completed by facile electron injections into the tricopper catalysts from the electrode. This technology leads to dramatic enhancements in performance of the catalysts toward methane oxidation. Unprecedented turnover frequencies (>40 min-1) and high product throughputs (turnover numbers >30 000 in 12 h) are achieved for this challenging chemical transformation in water under ambient conditions. The technology is green and suitable for on-site direct conversion of methane into methanol.

Selective Oxidation of Simple Aromatics Catalyzed by Nano-Biomimetic Metal Oxide Catalysts: A Mini Review.

The process of selective oxy-functionalization of hydrocarbons using peroxide, O3, H2O2, O2, and transition metals can be carried out by the reactive oxygen species such as hydroxyl/hydroperoxyl radical and/or metal oxygenated species generated in the catalytic reaction. Thus, a variety of mechanisms have been proposed for the selective catalytic oxidation of various hydrocarbons including light alkanes, olefins, and simple aromatics by the biological metalloproteins and their biomimetics either in their homogeneous or heterogeneous platforms. Most studies involving these metalloproteins are Fe or Cu monooxygenases. The pathways carried out by these metalloenzymes in the oxidation of C-H bonds invoke either radical reaction mechanisms including Fenton's chemistry and hydrogen atom transfer followed by radical rebound reaction mechanism or electrophilic oxygenation/O-atom transfer by metal-oxygen species. In this review, we discuss the metal oxide nano-catalysts obtained from metal salts/molecular precursors (M = Cu, Fe, and V) that can easily form in situ through the oxidation of substrates using H2O2(aq) in CH3CN, and be facilely separated from the reaction mixtures as well as recycled for several times with comparable catalytic efficiency for the highly selective conversion from hydrocarbons including aromatics to oxygenates. The mechanistic insights revealed from the oxy-functionalization of simple aromatics mediated by the novel biomimetic metal oxide materials can pave the way toward developing facile, cost-effective, and highly efficient nano-catalysts for the selective partial oxidation of simple aromatics.

A Carbon Electrode Functionalized by a Tricopper Cluster Complex: Overcoming Overpotential and Production of Hydrogen Peroxide in the Oxygen Reduction Reaction.

A study of the oxygen reduction reaction (ORR) on a screen printed carbon electrode surface mediated by the tricopper cluster complex Cu3 (7-N-Etppz(CH2 OH)) dispersed on electrochemically reduced carbon black, where 7-N-Etppz(CH2 OH) is the ligand 3,3'-(6-(hydroxymethyl)-1,4-diazepane-1,4-diyl)bis(1-(4-ethyl piperazin-1-yl)propan-2-ol), is described. Onset oxygen reduction potentials of about 0.92 V and about 0.77 V are observed at pH 13 and pH 7 vs. the reversible hydrogen electrode, which are comparable to the best values reported for any synthetic copper complex. Based on half-wave potentials (E1/2 ), the corresponding overpotentials are about 0.42 V and about 0.68 V, respectively. Kinetic studies indicate that the trinuclear copper catalyst can accomplish the 4 e- reduction of O2 efficiently and the ORR is accompanied by the production of only small amounts of H2 O2 . The involvement of the copper triad in the O2 activation process is also verified.

Design and Synthesis of Chiral Diene Ligands for RhI -Catalyzed Enantioselective Arylation of N-DPP-protected Aldimines: Synthesis of the Antifungal Agent Bifonazole.

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the RhI -catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl (N-DPP)-protected aldimines. Unlike the analogous RhI -catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31-99 % and with ee values up to 91-99 %. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole (13).

Synthesis and biological evaluation of helioxanthin analogues.

Helioxanthin and analogues have been demonstrated to suppress gene expression of human hepatitis B virus. In the continuous attempt to optimize antiviral activity, various structural motifs were grafted on the helioxanthin scaffold. Many such analogues were synthesized and evaluated for their anti-hepatitis B virus activity. Structure-activity relationships of these helioxanthin derivatives are also discussed. Among these new compounds, 15 exhibits the highest activity against HBV (EC50=0.06 µM). This compound can suppress viral surface antigen and DNA expression. Furthermore, viral RNA is also diminished while the core promoter is deactivated upon treatment by 15. A plausible working mechanism is postulated. Our results establish helioxanthin lignans as potent anti-HBV agents with unique mode of action. Since their antiviral mechanism is distinct from current nucleoside/nucleotide drugs, helioxanthin lignans constitute a potentially new class of anti-HBV agents for combination therapy.

Preparation of chiral 3-arylpyrrolidines via the enantioselective 1,4-addition of arylboronic acids to fumaric esters catalyzed by Rh(I)/chiral diene complexes.

A highly efficient rhodium-catalyzed protocol for the preparation of 2-arylsuccinic esters and 3-arylpyrrolidines of high optical purity has been achieved. In the presence of 1 mol % of a chiral diene/Rh(I) catalyst, asymmetric addition of various arylboronic acids to di-tert-butyl fumarate (3c) provides the corresponding adducts in up to 99% yield and 94→99.5% ee. Excellent enantioselectivities were also observed in the regio- and enantioselective conjugate addition of phenylboronic acid (4a) to compound 3e.

Synthesis and the biological evaluation of arylnaphthalene lignans as anti-hepatitis B virus agents.

We have previously shown that helioxanthin can suppress human hepatitis B virus gene expression. A series of helioxanthin analogues were synthesized and evaluated for their anti-hepatitis B virus activity. Modifications at the lactone rings and methylenedioxy unit of helioxanthin can modulate the antiviral activity. Among them, compound 32 is the most effective anti-HBV agent. Compound 32 can suppress the secretion of viral surface antigen and e antigen in HepA2 cells with EC(50) values of 0.06 and 0.14 microM, respectively. Compound 32 not only inhibited HBV DNA with wild-type and lamivudine-resistant strain but also suppressed HBV mRNA, core protein and viral promoters. In this study, a full account of the preparation, structure-activity relationships of helioxanthin analogues, and the possible mechanism of anti-HBV activity of this class of compounds are presented. This type of compounds possesses unique mode of action differing from existing therapeutic drugs. They are potentially new anti-HBV agents.

Helioxanthin inhibits interleukin-1 beta-induced MIP-1 beta production by reduction of c-jun expression and binding of the c-jun/CREB1 complex to the AP-1/CRE site of the MIP-1 beta promoter in Huh7 cells.

An elevated level of macrophage inflammatory protein-1beta (MIP-1beta) induced by IL-1beta has been correlated with chronic hepatic inflammatory disease. However, molecular mechanism of IL-1beta-induced MIP-1beta expression in hepatic cells is obscure. Previously, we reported the mechanism of the anti-hepatitis B virus (HBV) activity of helioxanthin (HE-145). Here, we demonstrated that HE-145 inhibited IL-1beta-induced MIP-1beta expression in a dose-dependent manner in Huh7 cells. To understand the mode of action of HE-145, we first examined how IL-1beta induced MIP-1beta expression at the molecular level. Using selective inhibitors, we found that JNK and p38 pathways participated in IL-1beta-induced MIP-1beta expression. HE-145 specifically suppressed IL-1beta-induced c-jun mRNA and protein expression and prevented c-jun-mediated AP-1 DNA-binding activity, whereas it had no effect on IL-1beta-induced activation of JNK, p38 and ATF2. Further studies indicated that HE-145 may downregulate c-jun mRNA expression directly at transcriptional level without requirement of de novo protein synthesis. Mutational analysis and supershift assays indicated that IL-1beta stimulated c-jun and CREB1 binding to the essential AP-1/CRE site of the MIP-1beta promoter. The inhibitory effect of HE-145 on IL-1beta-induced MIP-1beta promoter activity was completely reversed by overexpressing c-jun. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay consistently revealed that HE-145 reduced c-jun binding to the AP-1/CRE site in vitro and in vivo. Our results established a major role for c-jun in IL-1beta-induced MIP-1beta expression in hepatic cells. The reduction in IL-1beta-induced c-jun expression and subsequent binding of the c-jun/CREB1 complex to AP-1/CRE site mainly contributed to the inhibitory action of HE-145 on IL-1beta-induced MIP-1beta production.

The role of helioxanthin in inhibiting human hepatitis B viral replication and gene expression by interfering with the host transcriptional machinery of viral promoters.

A non-nucleosidic compound, Helioxanthin (HE-145), was found to suppress HBV gene expression and replication in HCC cells. To understand the molecular mode of action of HE-145 on HBV gene expression, the effects of HE-145 on four viral promoter activities using luciferase as a reporter were examined. It was found that HE-145 selectively suppresses surface antigen promoter II (SPII) and core promoter (CP) but has no effect on surface antigen promoter I (SPI) or promoter for X gene (Xp). The suppressive effects of HE-145 on either SPII or CP activity is liver-specific, since no suppressive activity of HE-145 was observed when CP or SPII promoter activity was assayed in non-liver cells such as HeLa or 293T. To examine the mode of action of HE-145, EMSA analysis revealed that HE-145 decreased the DNA-binding activity of nuclear extract of HepA2 cells to specific cis element of HBV promoter for core antigen, including peroxisome proliferator-activated receptors (PPARs), PPARs binding site (PPRE), alpha-fetoprotein transcription factor (FTF), and Sp1. Ectopic expression of PPAR gamma or HNF4 alpha partially reversed the HE-145-mediated suppression of HBV RNA. Therefore, HE-145 may represent a novel class of anti-HBV agents which selectively modulate transcriptional machinery of human liver cells to suppress HBV gene expression and replication.