Tungsten Oxide Dispersed on Silica as Robust and Readily Available Oxo/Imido Heterometathesis Catalyst.

Continuing our investigation of catalytic oxo/imido heterometathesis as novel water-free method for C=N bond construction, we report here the application of classical transition metal oxides dispersed on silica (MOx/SiO2, M=V, Mo, W) as cheap, robust and readily available alternative to the catalysts prepared via Surface Organometallic Chemistry (SOMC). The oxide materials demonstrated activity in heterometathetical imidation of ketones, WO3/SiO2 being the most efficient. We also describe a new well-defined supported W imido complex (≡SiO)W(=NMes)2(Me2Pyr) (Mes=2,4,6-Me3C6H2, Me2Pyr=2,5-dimethylpyrrolyl) and characterize it with SOMC protocols, which allowed us to identify the position of W on the oxo/imido heterometathesis activity scale (Mo

Readily available Ti-based in situ catalytic system for oxo/imido heterometathesis.

We investigate Ti(NEt2)4 supported on silica dehydroxylated at 700 °C as an easily accessible pre-catalyst for oxo/imido heterometathesis reactions. Being activated with TolNH2, the supported Ti amide (SiO)Ti(NEt2)3 (1) demonstrates catalytic activity in the imidation of ketones with N-sulfinylamines comparable with the most active previously described well-defined imido catalyst (SiO)Ti(NtBu)(Me2Pyr)(py)2 (2) (Me2Pyr = 2,5-dimethylpyrrolyl), which implies the in situ formation of surface imido species in this system. The materials obtained via treatment of 1 with anilines (TolNH2 (1a) and p-MeOC6H415NH2 (1b)) were studied with IR, EA and 1H, 13C, 15N and 2D solid-state NMR, although the proposed imido intermediate has not been detected, pointing towards tris-amides (SiO)Ti(NHC6H4X)3 (X = Me, OMe) being the major surface species in the isolated materials 1a and 1b. The system 1/TolNH2 was tested in a range of imidation reactions and demonstrated excellent performance for express high-yielding preparation of ketimines, formamidines, lactone imidates and sulfurdiimines, making it a convenient alternative to the well-defined supported Ti imido catalysts.

TIGIT is a key inhibitory checkpoint receptor in lymphoma.

BACKGROUND: PD-1 checkpoint blockade therapy (CBT) has greatly benefited patients with select solid tumors and lymphomas but has limited efficacy against diffuse large B-cell lymphoma (DLBCL). Because numerous inhibitory checkpoint receptors have been implicated in driving tumor-specific T cell dysfunction, we hypothesized that combinatorial CBT would enhance the activity of anti-PD-1-based therapy in DLBCL. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a coinhibitory receptor expressed on dysfunctional tumor-infiltrating T cells, and TIGIT blockade has demonstrated encouraging activity in combination with PD-1 blockade in murine tumor models and in clinical studies. However, the degree to which TIGIT mediates T cell dysfunction in DLBCL has not been fully explored. RESULTS: Here, we demonstrate that TIGIT is broadly expressed on lymphoma-infiltrating T cells (LITs) across a variety of human lymphomas and is frequently coexpressed with PD-1. TIGIT expression is particularly common on LITs in DLBCL, where TIGIT+ LITs often form distinct cellular communities and exhibit significant contact with malignant B cells. TIGIT+/PD-1+ LITs from human DLBCL and murine lymphomas exhibit hypofunctional cytokine production on ex vivo restimulation. In mice with established, syngeneic A20 B-cell lymphomas, TIGIT or PD-1 mono-blockade leads to modest delays in tumor outgrowth, whereas PD-1 and TIGIT co-blockade results in complete rejection of A20 lymphomas in most mice and significantly prolongs survival compared with mice treated with monoblockade therapy. CONCLUSIONS: These results provide rationale for clinical investigation of TIGIT and PD-1 blockade in lymphomas, including DLBCL.

Direct imidation of lactones via catalytic oxo/imido heterometathesis.

We report the first examples of direct imidation of lactones giving the corresponding cyclic imidates via oxo/imido heterometathesis with N-sulfinylamines catalysed by a well-defined silica-supported Ti imido complex.

Catalytic Oxo/Imido Heterometathesis by a Well-Defined Silica-Supported Titanium Imido Complex.

Grafting Ti(=NtBu)(Me2 Pyr)2 (py)2 (Me2 Pyr= 2,5-dimethylpyrrolyl, py=pyridine) onto the surface of silica partially dehydroxylated at 700 °C gives the well-defined silica-supported Ti imido complex (≡SiO)Ti(=NtBu)(Me2 Pyr)(py)2 , which is fully characterized by IR and solid-state NMR spectroscopy as well as elemental and mass balance analyses. While stoichiometric imido-transfer reactivity is typical for Ti imides, the obtained surface complex is unique in that it enables catalytic transformations involving Ti imido and oxo intermediates. In particular, it efficiently catalyzes imidation of carbonyl compounds with N-sulfinylamines by oxo/imido heterometathesis.

Time-Resolved In†Situ MAS NMR Monitoring of the Nucleation and Growth of Zeolite BEA Catalysts under Hydrothermal Conditions.

Time-resolved 13 C, 23 Na, 27 Al, and 29 Si MAS NMR has been applied in situ for monitoring the hydrothermal synthesis of zeolite BEA. Isotopic labelling with 29 Si and 13 C isotopes has been used to follow the fate of siliceous species and structure directing agent ((13 CH3 -CH2 )4 NOH). Two mechanistic pathways, namely solution-mediated and solid-solid hydrogel rearrangement have been distinguished for two synthesis procedures studied. The mechanisms of structure-directing behavior of TEA+ cations in two reaction pathways have been elucidated. The results show that multinuclear MAS NMR can serve as a superior tool for monitoring hydrothermal synthesis of various solids including zeolites, zeotypes, mesoporous materials, metal-organic frameworks and so on and for the design of novel outstanding materials for different applications.

Effects of cooperative ion-channel interactions on the dynamics of excitable membranes.

Cooperative interactions between ion channels are known to exist, but have so far received relatively little attention in the study of excitable membranes. Based on bifurcation analysis and stochastic simulations of an extended Morris-Lecar model, we show that cooperativity and anticooperativity can modify the range of sustained firing and cell-intrinsic noise, induce multistability, and account for a number of experimental observations, including prolongation of action-potential duration. We hypothesize that channel interactions could be an efficient mechanism to regulate the activity of neurons or cardiac muscle cells.