The insertion of an olefin into a preformed metal–carbon bond is a common mechanism for transition‐metal‐catalyzed olefin polymerization. However, in one important industrial catalyst, the Phillips ...catalyst, a metal–carbon bond is not present in the precatalyst. The Phillips catalyst, CrO3 dispersed on silica, polymerizes ethylene without an activator. Despite 60 years of intensive research, the active sites and the way the first CrC bond is formed remain unknown. We synthesized well‐defined dinuclear CrII and CrIII sites on silica. Whereas the CrII material was a poor polymerization catalyst, the CrIII material was active. Poisoning studies showed that about 65 % of the CrIII sites were active, a far higher proportion than typically observed for the Phillips catalyst. Examination of the spent catalyst and isotope labeling experiments showed the formation of a Si–(μ‐OH)–CrIII species, consistent with an initiation mechanism involving the heterolytic activation of ethylene at CrIIIO bonds.
Three is better than two: CrIII silicates, in contrast to the CrII analogues, were found to be efficient ethylene‐polymerization catalysts that initiate the reaction without a cocatalyst through the heterolytic splitting of an ethylene CH bond across a CrO bond (see picture). This study provides clues about the active sites and initiation mechanism of the industrial Phillips catalyst.
Use of doravirine (DOR), a new nonnucleoside reverse-transcriptase inhibitors recently approved for HIV treatment, is still unclear in clinical practice and real-life data are scarce. We ...retrospectively investigated the rationale for switching people with HIV to DOR-containing/-based regimens in a real-life cohort. Among 132 patients (68.9% males, median age 56 years), the main reasons to start DOR were prevention of toxicities (39.4%) and dyslipidemia (18.2%). DOR was combined with integrase inhibitors in 40.9% cases, and in 25.7% of patients, DOR was prescribed without availability of a genotypic resistance test. Twenty-four weeks after the switch to DOR-containing/-based regimens, no significant changes in CD4+ T-cell count, CD4/CD8 ratio, detectable HIV-RNA, serum creatinine levels, and body weight were detected. By contrast, a significant reduction in lipids (both cholesterol and triglycerides) was observed in 52 patients for whom a follow-up assessment was available (P = .008 and .01, respectively). Our data confirmed that switching to DOR-containing/-based regimens may have a favorable impact on lipid profile and a neutral impact on weight gain. However, more data are needed to support its use in patients who do not have a genotypic test available or have an extensive nonnucleoside reverse-transcriptase inhibitors-associated resistance, as well as its use in a dual regimen, especially in combination with second-generation integrase inhibitors.
The insertion of an olefin into a preformed metal-carbon bond is a common mechanism for transition-metal-catalyzed olefin polymerization. However, in one important industrial catalyst, the Phillips ...catalyst, a metal-carbon bond is not present in the precatalyst. The Phillips catalyst, CrO3 dispersed on silica, polymerizes ethylene without an activator. Despite 60 years of intensive research, the active sites and the way the first CrC bond is formed remain unknown. We synthesized well-defined dinuclear Cr(II) and Cr(III) sites on silica. Whereas the Cr(II) material was a poor polymerization catalyst, the Cr(III) material was active. Poisoning studies showed that about 65 % of the Cr(III) sites were active, a far higher proportion than typically observed for the Phillips catalyst. Examination of the spent catalyst and isotope labeling experiments showed the formation of a Si-(μ-OH)-Cr(III) species, consistent with an initiation mechanism involving the heterolytic activation of ethylene at Cr(III) O bonds.
Abstract
The insertion of an olefin into a preformed metal–carbon bond is a common mechanism for transition‐metal‐catalyzed olefin polymerization. However, in one important industrial catalyst, the ...Phillips catalyst, a metal–carbon bond is not present in the precatalyst. The Phillips catalyst, CrO
3
dispersed on silica, polymerizes ethylene without an activator. Despite 60 years of intensive research, the active sites and the way the first CrC bond is formed remain unknown. We synthesized well‐defined dinuclear Cr
II
and Cr
III
sites on silica. Whereas the Cr
II
material was a poor polymerization catalyst, the Cr
III
material was active. Poisoning studies showed that about 65 % of the Cr
III
sites were active, a far higher proportion than typically observed for the Phillips catalyst. Examination of the spent catalyst and isotope labeling experiments showed the formation of a Si–(μ‐OH)–Cr
III
species, consistent with an initiation mechanism involving the heterolytic activation of ethylene at Cr
III
O bonds.
Remdesivir shortens time to recovery in adults with severe coronavirus disease 2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes in children with severe ...COVID-19 treated with remdesivir.
Seventy-seven hospitalized patients <18 years old with confirmed severe acute respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-use program between March 21 and April 22, 2020. The intended remdesivir treatment course was 10 days (200 mg on day 1 and 100 mg daily subsequently for children ≥40 kg and 5 mg/kg on day 1 and 2.5 mg/kg daily subsequently for children <40 kg, given intravenously). Clinical data through 28 days of follow-up were collected.
Median age was 14 years (interquartile range 7-16, range <2 months to 17 years). Seventy-nine percent of patients had ≥1 comorbid condition. At baseline, 90% of children required supplemental oxygen and 51% required invasive ventilation. By day 28 of follow-up, 88% of patients had a decreased oxygen-support requirement, 83% recovered, and 73% were discharged. Among children requiring invasive ventilation at baseline, 90% were extubated, 80% recovered, and 67% were discharged. There were 4 deaths, of which 3 were attributed to COVID-19. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to COVID-19 or comorbid conditions. Laboratory abnormalities, including elevations in transaminase levels, were common; 61% were grades 1 or 2.
Among 77 children treated with remdesivir for severe COVID-19, most recovered and the rate of serious adverse events was low.
PDF
