The active metabolite of leflunomide, A77 1726, interferes with dendritic cell function

Leflunomide, a potent disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA), exhibits anti-inflammatory, antiproliferative and immunosuppressive effects. Although most of the beneficial effects of leflunomide have been attributed to its antimetabolite activity, mainly in T cells, other targets accounting for its potency might still exist. Because of mounting evidence for a prominent role of dendritic cells (DCs) in the initiation and maintenance of the immune response in RA, we analyzed the effect of the active metabolite of leflunomide (A77 1726; LEF-M) on phenotype and function of human myleloid DCs at several stages in their life cycle. Importantly, DCs differentiated in the presence of LEF-M exhibited an altered phenotype, with largely reduced surface expression of the critical co-stimulatory molecules CD40 and CD80. Furthermore, treatment of DCs during the differentiation or maturation phase with LEF-M aborted successful DC maturation. Exogenous addition of uridine revealed that DC modulation by LEF-M was independent of its proposed ability as an antimetabolite. In addition, the ability of DCs to initiate T-cell proliferation and to produce the proinflammatory cytokines IL-12 and tumour necrosis factor-α was markedly impaired by LEF-M treatment. As a molecular mechanism, transactivation of nuclear factor-κB, an transcription factor essential for proper DC function, was completely suppressed in DCs treated with LEF-M. These data indicate that interference with several aspects of DC function could significantly contribute to the beneficial effects of leflunomide in inflammatory diseases, including RA

Steering the methanol steam reforming reactivity of intermetallic Cu-In compounds by redox activation: stability vs. formation of an intermetallic compound-oxide interface.

To compare the inherent methanol steam reforming properties of intermetallic compounds and a corresponding intermetallic compound-oxide interface, we selected the Cu-In system as a model to correlate the stability limits, self-activation and redox activation properties with the catalytic performance. Three distinct intermetallic Cu-In compounds - Cu7In3, Cu2In and Cu11In9 - were studied both in an untreated and redox-activated state resulting from alternating oxidation-reduction cycles. The stability of all studied intermetallic compounds during methanol steam reforming (MSR) operation is essentially independent of the initial stoichiometry and all accordingly resist substantial structural changes. The inherent activity under batch MSR conditions is highest for Cu2In, corroborating the results of a Cu2In/In2O3 sample accessed through reactive metal-support interaction. Under flow MSR operation, Cu7In3 displays considerable deactivation, while Cu2In and Cu11In9 feature stable performance at simultaneously high CO2 selectivity. The missing significant self-activation is most evident in the operando thermogravimetric experiments, where no oxidation is detected for any of the intermetallic compounds. In situ X-ray diffraction allowed us to monitor the partial decomposition and redox activation of the Cu-In intermetallic compounds into Cu0.9In0.1/In2O3 (from Cu7In3), Cu7In3/In2O3 (from Cu2In) and Cu7In3/Cu0.9In0.1/In2O3 (from Cu11In9) interfaces with superior MSR performance compared to the untreated samples. Although the catalytic profiles appear surprisingly similar, the latter interface with the highest indium content exhibits the least deactivation, which we explain by formation of stabilizing In2O3 patches under MSR conditions

Steering the methanol steam reforming reactivity of intermetallic Cu-In compounds by redox activation: stability vs. formation of an intermetallic compound-oxide interface.

To compare the inherent methanol steam reforming properties of intermetallic compounds and a corresponding intermetallic compound-oxide interface, we selected the Cu-In system as a model to correlate the stability limits, self-activation and redox activation properties with the catalytic performance. Three distinct intermetallic Cu-In compounds - Cu7In3, Cu2In and Cu11In9 - were studied both in an untreated and redox-activated state resulting from alternating oxidation-reduction cycles. The stability of all studied intermetallic compounds during methanol steam reforming (MSR) operation is essentially independent of the initial stoichiometry and all accordingly resist substantial structural changes. The inherent activity under batch MSR conditions is highest for Cu2In, corroborating the results of a Cu2In/In2O3 sample accessed through reactive metal-support interaction. Under flow MSR operation, Cu7In3 displays considerable deactivation, while Cu2In and Cu11In9 feature stable performance at simultaneously high CO2 selectivity. The missing significant self-activation is most evident in the operando thermogravimetric experiments, where no oxidation is detected for any of the intermetallic compounds. In situ X-ray diffraction allowed us to monitor the partial decomposition and redox activation of the Cu-In intermetallic compounds into Cu0.9In0.1/In2O3 (from Cu7In3), Cu7In3/In2O3 (from Cu2In) and Cu7In3/Cu0.9In0.1/In2O3 (from Cu11In9) interfaces with superior MSR performance compared to the untreated samples. Although the catalytic profiles appear surprisingly similar, the latter interface with the highest indium content exhibits the least deactivation, which we explain by formation of stabilizing In2O3 patches under MSR conditions

The sol–gel autocombustion as a route towards highly CO 2 -selective, active and long-term stable Cu/ZrO 2 methanol steam reforming catalysts

Ploner, Kevin; Nezhad, Parastoo Delir Kheyrollahi; Gili, Albert; Kamutzki, Franz; Gurlo, Aleksander; Doran, Andrew; Cao, Pengfei; Heggen, Marc; Köwitsch, Nicolas; Armbrüster, Marc; "The sol–gel autocombustion as a route towards highly CO 2-selective, active and long-term stable Cu/ZrO 2 methanol steam reforming catalysts", Mater. Chem. Front., (2021) 5, 5093-5105, DOI: 10.1039/D1QM00641JThe adaption of the sol–gel autocombustion method to the Cu/ZrO2 system opens new pathways for the specific optimisation of the activity, long-term stability and CO2 selectivity of methanol steam reforming (MSR) catalysts. Calcination of the same post-combustion precursor at 400 °C, 600 °C or 800 °C allows accessing Cu/ZrO2 interfaces of metallic Cu with either amorphous, tetragonal or monoclinic ZrO2, influencing the CO2 selectivity and the MSR activity distinctly different. While the CO2 selectivity is less affected, the impact of the post-combustion calcination temperature on the Cu and ZrO2 catalyst morphology is more pronounced. A porous and largely amorphous ZrO2 structure in the sample, characteristic for sol–gel autocombustion processes, is obtained at 400 °C. This directly translates into superior activity and long-term stability in MSR compared to Cu/tetragonal ZrO2 and Cu/monoclinic ZrO2 obtained by calcination at 600 °C and 800 °C. The morphology of the latter Cu/ZrO2 catalysts consists of much larger, agglomerated and non-porous crystalline particles. Based on aberration-corrected electron microscopy, we attribute the beneficial catalytic properties of the Cu/amorphous ZrO2 material partially to the enhanced sintering resistance of copper particles provided by the porous support morphology