Palladium/IzQO-Catalyzed Coordination–Insertion Copolymerization of Ethylene and 1,1-Disubstituted Ethylenes Bearing a Polar Functional Group

Coordination–insertion copolymerization of ethylene with 1,1-disubstituted ethylenes bearing a polar functional group, such as methyl methacrylate (MMA), is a long-standing challenge in catalytic polymerization. The major obstacle for this process is the huge difference in reactivity of ethylene versus 1,1-disubstituted ethylenes toward both coordination and insertion. Herein we report the copolymerization of ethylene and 1,1-disubstituted ethylenes by using an imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene-supported palladium catalyst. Various types of 1,1-disubstituted ethylenes were successfully incorporated into the polyethylene chain. In-depth characterization of the obtained copolymers and mechanistic inferences drawn from stoichiometric reactions of alkylpalladium complexes with methyl methacrylate and ethylene indicate that the copolymerization proceeds by the same coordination–insertion mechanism that has been postulated for ethylene

Synthesis and Reactivity of Methylpalladium Complexes Bearing a Partially Saturated IzQO Ligand

A saturated N-heterocyclic carbene–phenolate bidentate ligand, 3,3a,4,5-tetrahydroimidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (SIzQO), was synthesized and characterized. The SIzQO ligand was then treated with PdClMe­(pyridine)₂ and [Pd­(μ-Cl)­Me­(2,6-lutidine)]₂, which afforded <i>C</i>,<i>C</i>-<i>cis</i>-(SIzQO)­PdMe­(pyridine) and the thermodynamically unstable <i>trans</i> isomer <i>C</i>,<i>C</i>-<i>trans</i>-(SIzQO)­PdMe­(2,6-lutidine), respectively. The latter isomerizes at 40 °C into the corresponding <i>cis</i> isomer via a dissociative mechanism. These palladium/SIzQO complexes catalyze the polymerization of ethylene at 100–120 °C, although the catalytic activity is lower than that of a previously reported palladium/imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (IzQO) system

Palladium/IzQO-Catalyzed Coordination–Insertion Copolymerization of Ethylene and 1,1-Disubstituted Ethylenes Bearing a Polar Functional Group

Coordination–insertion copolymerization of ethylene with 1,1-disubstituted ethylenes bearing a polar functional group, such as methyl methacrylate (MMA), is a long-standing challenge in catalytic polymerization. The major obstacle for this process is the huge difference in reactivity of ethylene versus 1,1-disubstituted ethylenes toward both coordination and insertion. Herein we report the copolymerization of ethylene and 1,1-disubstituted ethylenes by using an imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene-supported palladium catalyst. Various types of 1,1-disubstituted ethylenes were successfully incorporated into the polyethylene chain. In-depth characterization of the obtained copolymers and mechanistic inferences drawn from stoichiometric reactions of alkylpalladium complexes with methyl methacrylate and ethylene indicate that the copolymerization proceeds by the same coordination–insertion mechanism that has been postulated for ethylene

Synthesis and Reactivity of Methylpalladium Complexes Bearing a Partially Saturated IzQO Ligand

A saturated N-heterocyclic carbene–phenolate bidentate ligand, 3,3a,4,5-tetrahydroimidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (SIzQO), was synthesized and characterized. The SIzQO ligand was then treated with PdClMe­(pyridine)₂ and [Pd­(μ-Cl)­Me­(2,6-lutidine)]₂, which afforded <i>C</i>,<i>C</i>-<i>cis</i>-(SIzQO)­PdMe­(pyridine) and the thermodynamically unstable <i>trans</i> isomer <i>C</i>,<i>C</i>-<i>trans</i>-(SIzQO)­PdMe­(2,6-lutidine), respectively. The latter isomerizes at 40 °C into the corresponding <i>cis</i> isomer via a dissociative mechanism. These palladium/SIzQO complexes catalyze the polymerization of ethylene at 100–120 °C, although the catalytic activity is lower than that of a previously reported palladium/imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (IzQO) system

Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer

Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient’s prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition

Elucidating the Key Role of Phosphine−Sulfonate Ligands in Palladium-Catalyzed Ethylene Polymerization: Effect of Ligand Structure on the Molecular Weight and Linearity of Polyethylene

The mechanism of linear polyethylene formation catalyzed by palladium/phosphine−sulfonate and the effect of the ligand structure on the catalytic performance, such as linearity and molecular weight of the polyethylene, were reinvestigated theoretically and experimentally. We used dispersion-corrected density functional theory (DFT-D3) to study the entire mechanism of polyethylene formation from (R₂PC₆H₄SO₃)­PdMe­(2,6-lutidine) (R = Me, <i>t-</i>Bu) and elucidated the key steps that determine the molecular weight and linearity of the polyethylene. The alkylpalladium ethylene complex is the key intermediate for both linear propagation and β-hydride elimination from the growing polymer chain. On the basis of the key species, the effects of substituents on the phosphorus atom (R = <i>t-</i>Bu, <i>i</i>-Pr, Cy, Men, Ph, 2-MeOC₆H₄, biAr) were further investigated theoretically to explain the experimental results in a comprehensive manner. Thus, the experimental trend of molecular weights of polyethylene could be correlated to the ΔΔ<i><i>G</i></i>^⧧ value between (i) the transition state of linear propagation and (ii) the transition state of the path for ethylene dissociation leading to β-hydride elimination. Moreover, the experimental behavior of the catalysts under varied ethylene pressure was well explained by our computation on the small set of key species elucidated from the entire mechanism. In our additional experimental investigations, [<i>o</i>-Ani₂PC₆H₄SO₃]­PdH­[P­(<i>t</i>-Bu)₃] catalyzed a hydrogen/deuterium exchange reaction between ethylene and MeOD. The deuterium incorporation from MeOD into the main chain of polyethylene, therefore, can be explained by the incorporation of deuterated ethylene formed by a small amount of Pd–H species. These insights into the palladium/phosphine−sulfonate system provide a comprehensive understanding of how the phosphine−sulfonate ligands function to produce linear polyethylene