Dehydroalkylative Activation of CNN- and PNN-Pincer Ruthenium Catalysts for Ester Hydrogenation

Ruthenium–pincer complexes bearing CNN- and PNN-pincer ligands with diethyl- or diisopropylamino side groups, which have previously been reported to be active precatalysts for ester hydrogenation, undergo dehydroalkylation on heating in the presence of tricyclohexylphosphine to release ethane or propane, giving five-coordinate ruthenium(0) complexes containing a nascent imine functional group. Ethane or propane is also released under the conditions of catalytic ester hydrogenation, and time-course studies show that this release is concomitant with the onset of catalysis. A new PNN-pincer ruthenium(0)–imine complex is a highly active catalyst for ester hydrogenation at room temperature, giving up to 15 500 turnovers with no added base. This complex was shown to react reversibly at room temperature with two equivalents of hydrogen to give a ruthenium­(II)–dihydride complex, where the imine functionality has been hydrogenated to give a protic amine side group. These observations have potentially broad implications for the identities of catalytic intermediates in ester hydrogenation and related transformations

Dehydroalkylative Activation of CNN- and PNN-Pincer Ruthenium Catalysts for Ester Hydrogenation

Ruthenium–pincer complexes bearing CNN- and PNN-pincer ligands with diethyl- or diisopropylamino side groups, which have previously been reported to be active precatalysts for ester hydrogenation, undergo dehydroalkylation on heating in the presence of tricyclohexylphosphine to release ethane or propane, giving five-coordinate ruthenium(0) complexes containing a nascent imine functional group. Ethane or propane is also released under the conditions of catalytic ester hydrogenation, and time-course studies show that this release is concomitant with the onset of catalysis. A new PNN-pincer ruthenium(0)–imine complex is a highly active catalyst for ester hydrogenation at room temperature, giving up to 15 500 turnovers with no added base. This complex was shown to react reversibly at room temperature with two equivalents of hydrogen to give a ruthenium­(II)–dihydride complex, where the imine functionality has been hydrogenated to give a protic amine side group. These observations have potentially broad implications for the identities of catalytic intermediates in ester hydrogenation and related transformations

Table_1_Gross total resection and survival outcomes in elderly patients with spinal chordoma: a SEER-based analysis.docx

ObjectiveThe association between aggressive resection and improved survival for adult spinal chordoma patients has not been well characterized in the geriatric population. Thus, the present study aimed to elucidate the relationship between gross total resection (GTR) and survival outcomes for patients across different age groups.MethodsThe authors isolated all adult patients diagnosed with spinal chordoma from the 2000-2019 Surveillance, Epidemiology, and End Results database and divided patients into three surgical subgroups: no surgery, subtotal resection (STR), and GTR. Kaplan-Meier curves with a log-rank test were used to discern differences in overall survival (OS) between surgical subgroups. Univariate and multivariate analyses were used to identify prognostic factors of mortality.ResultsThere were 771 eligible patients: 227 (29.4%) received no surgery, 267 (34.6%) received STR, and 277 (35.9%) received GTR. Patients receiving no surgery had the lowest 5-year OS (45.2%), 10-year OS (17.6%), and mean OS (72.1 months). After stratifying patients by age, our multivariate analysis demonstrated that patients receiving GTR aged 40-59 (HR=0.26, CI=0.12-0.55, pConclusionGTR is associated with improved survival for middle-aged and elderly patients with spinal chordoma. Therefore, patients should not be excluded from aggressive resection on the basis of age alone. Rather, the decision to pursue surgery should be decided on an individual basis.</p

Dehydroalkylative Activation of CNN- and PNN-Pincer Ruthenium Catalysts for Ester Hydrogenation

Ruthenium–pincer complexes bearing CNN- and PNN-pincer ligands with diethyl- or diisopropylamino side groups, which have previously been reported to be active precatalysts for ester hydrogenation, undergo dehydroalkylation on heating in the presence of tricyclohexylphosphine to release ethane or propane, giving five-coordinate ruthenium(0) complexes containing a nascent imine functional group. Ethane or propane is also released under the conditions of catalytic ester hydrogenation, and time-course studies show that this release is concomitant with the onset of catalysis. A new PNN-pincer ruthenium(0)–imine complex is a highly active catalyst for ester hydrogenation at room temperature, giving up to 15 500 turnovers with no added base. This complex was shown to react reversibly at room temperature with two equivalents of hydrogen to give a ruthenium­(II)–dihydride complex, where the imine functionality has been hydrogenated to give a protic amine side group. These observations have potentially broad implications for the identities of catalytic intermediates in ester hydrogenation and related transformations

Unexpected CNN-to-CC Ligand Rearrangement in Pincer–Ruthenium Precatalysts Leads to a Base-Free Catalyst for Ester Hydrogenation

We report the conversion of a series of CNN–pincer–ruthenium complexes Ru­(CNN)­HCl­(CO) to a CC-chelated form Ru­(CC)­(PR3)2H­(CO) on reaction with sodium tert-butoxide and monodentate phosphines. When the phosphine is triphenylphosphine, cis-phosphine complexes form at room temperature, which convert to the trans isomer at elevated temperatures. When the phosphine is tricyclohexylphosphine, only the trans-phosphine isomer is observed. The CC-chelated complexes are active catalysts for the hydrogenation of esters, without the need for added base. The ligand structure–activity relationship in the series of CC-chelated complexes mirrors that in the precursor CNN-Ru complexes, potentially indicating a common catalytic mechanism. Density functional theory calculations establish a plausible mechanism for the CNN-to-CC rearrangement and demonstrate that this rearrangement is potentially reversible under the conditions of ester hydrogenation catalysis

Correlation analysis of peanut extract IgE titers and T cell cytokine production in response to peptide pool or peanut extract.

Correlation analysis of peanut extract IgE titers and T cell cytokine production in response to peptide pool or peanut extract.</p

Peanut extract and epitope responses and cytokine polarization in peanut symptomatic and non-symptomatic patients.

Magnitude and polarization of cytokine production (sum of IL-5, IL-10, IL-17 and IFNγ) in response to A-B) peanut extract and C-D) P19 pool is shown as SFC (spot forming cells) per 106 PBMC. On panel C, dashed line indicates positive response threshold of 70 SFC. Peanut sensitization status is indicated by IgE+. Sym = symptomatic (n = 15), Non-Sym = non-symtomatic (n = 14). Statistical comparison by Mann-Whitney test, one-tailed. *- p<0.05.</p

table_7_Urinary Peptides As a Novel Source of T Cell Allergen Epitopes.XLSX

<p>Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo). Posttranslationally modified peptides were common, accounting for almost half of total peptides. A pool consisting of 225 unique oligopeptides of 13 residues or more in size identified within was tested for its capacity to elicit T cell reactivity in mouse allergic donors. Following 14-day in vitro stimulation of PBMCs, we detected responses in about 95% of donors tested, directed against 116 distinct peptides, predominantly associated with Th2 cytokines (IL-5). Peptides from non-urine related proteins such as epidermal growth factor, collagen, and Beta-globin accounted for the highest response (15.9, 9.1, and 8.1% of the total response, respectively). Peptides derived from major urinary proteins (MUPs), kidney androgen-regulated protein (KAP), and uromodulin were the main T cell targets from kidney or urine related sources. Further ex vivo analysis of enrichment of 4-1BB expressing cells demonstrated that LoMo pool-specific T cell reactivity can be detected directly ex vivo in mouse allergic but not in non-allergic donors. Further cytometric analysis of responding cells revealed a bone fide memory T cell phenotype and confirmed their Th2 polarization. Overall, these data suggest that mouse urine-derived oligopeptides are a novel target for mouse allergy-associated T cell responses, which may contribute to immunopathological mechanisms in mouse allergy.</p

table_2_Urinary Peptides As a Novel Source of T Cell Allergen Epitopes.XLSX

<p>Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo). Posttranslationally modified peptides were common, accounting for almost half of total peptides. A pool consisting of 225 unique oligopeptides of 13 residues or more in size identified within was tested for its capacity to elicit T cell reactivity in mouse allergic donors. Following 14-day in vitro stimulation of PBMCs, we detected responses in about 95% of donors tested, directed against 116 distinct peptides, predominantly associated with Th2 cytokines (IL-5). Peptides from non-urine related proteins such as epidermal growth factor, collagen, and Beta-globin accounted for the highest response (15.9, 9.1, and 8.1% of the total response, respectively). Peptides derived from major urinary proteins (MUPs), kidney androgen-regulated protein (KAP), and uromodulin were the main T cell targets from kidney or urine related sources. Further ex vivo analysis of enrichment of 4-1BB expressing cells demonstrated that LoMo pool-specific T cell reactivity can be detected directly ex vivo in mouse allergic but not in non-allergic donors. Further cytometric analysis of responding cells revealed a bone fide memory T cell phenotype and confirmed their Th2 polarization. Overall, these data suggest that mouse urine-derived oligopeptides are a novel target for mouse allergy-associated T cell responses, which may contribute to immunopathological mechanisms in mouse allergy.</p