Preparation of Neutral trans - Cis [Ru(O2CR)2P2(NN)], Cationic [Ru(O2CR)P2(NN)](O2CR) and Pincer [Ru(O2CR)(CNN)P2] (P = PPh3, P2= diphosphine) Carboxylate Complexes and their Application in the Catalytic Carbonyl Compounds Reduction

The diacetate complexes trans-[Ru(\u3ba1-OAc)2(PPh3)2(NN)] (NN = ethylenediamine (en) (1), 2-(aminomethyl)pyridine (ampy) (2), 2-(aminomethyl)pyrimidine (ampyrim) (3)) have been isolated in 76-88% yield by reaction of [Ru(\u3ba2-OAc)2(PPh3)2] with the corresponding nitrogen ligands. The ampy-type derivatives 2 and 3 undergo isomerization to the thermodynamically most stable cationic complexes [Ru(\u3ba1-OAc)(PPh3)2(NN)]OAc (2a and 3a) and cis-[Ru(\u3ba1-OAc)2(PPh3)2(NN)] (2b and 3b) in methanol at RT. The trans-[Ru(\u3ba1-OAc)2(P2)2] (P2 = dppm (4), dppe (5)) compounds have been synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] by reaction with the suitable diphosphine in toluene at 95 \ub0C. The complex cis-[Ru(\u3ba1-OAc)2(dppm)(ampy)](6) has been obtained from [Ru(\u3ba2-OAc)2(PPh3)2] and dppm in toluene at reflux and reaction with ampy. The derivatives trans-[Ru(\u3ba1-OAc)2P2(NN)] (7-16; NN = en, ampy, ampyrim, 8-aminoquinoline; P2 = dppp, dppb, dppf, (R)-BINAP) can be easily synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] with a diphosphine and treatment with the NN ligands at RT. Alternatively these compounds have been prepared from trans-[Ru(OAc)2(PPh3)2(NN)] by reaction with the diphosphine in MEK at 50 \ub0C. The use of (R)-BINAP affords trans-[Ru(\u3ba1-OAc)2((R)-BINAP)(NN)] (NN = ampy (11), ampyrim (15)) isolated as single stereoisomers. Treatment of the ampy-type complexes 8-15 with methanol at RT leads to isomerization to the cationic derivatives [Ru(\u3ba2-OAc)P2(NN)]OAc (8a-15a; NN = ampy, ampyrim; P2 = dppp, dppb, dppf, (R)-BINAP). Similarly to 2, the dipivalate trans-[Ru(\u3ba1-OPiv)2(PPh3)2(ampy)] (18) is prepared from [Ru(\u3ba2-OPiv)2(PPh3)2] (17) and ampy in CHCl3. The pincer acetate [Ru(\u3ba1-OAc)(CNNOMe)(PPh3)2] (19) has been synthesized from [Ru(\u3ba2-OAc)2(PPh3)2] and HCNNOMe ligand in 2-propanol with NEt3 at reflux. In addition, the dppb pincer complexes [Ru(\u3ba1-OAc)(CNN)(dppb)] (CNN = AMTP (20), AMBQPh (21)) have been obtained from [Ru(\u3ba2-OAc)2(PPh3)2], dppb, and HAMTP or HAMBQPh with NEt3, respectively. The acetate NN and pincer complexes are active in transfer hydrogenation with 2-propanol and hydrogenation with H2 of carbonyl compounds at S/C values of up to 10000 and with TOF values of up to 160000 h-1

New N-phenylpyrrolamide DNA gyrase B inhibitors: Optimization of efficacy and antibacterial activity

The ATP binding site located on the subunit B of DNA gyrase is an attractive target for the development of new antibacterial agents. In recent decades, several small-molecule inhibitor classes have been discovered but none has so far reached the market. We present here the discovery of a promising new series of N-phenylpyrrolamides with low nanomolar IC50 values against DNA gyrase, and submicromolar IC50 values against topoisomerase IV from Escherichia coil and Staphylococcus aureus. The most potent compound in the series has an IC50 value of 13 nM against E. coil gyrase. Minimum inhibitory concentrations (MICs) against Gram-positive bacteria are in the low micromolar range. The oxadiazolone derivative with an IC50 value of 85 nM against E. coli DNA gyrase displays the most potent antibacterial activity, with MIC values of 1.56 mu M against Enterococcus faecalis, and 3.13 mu M against wild type S. aureus, methicillinresistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The activity against wild type E. coli in the presence of efflux pump inhibitor phenylalanine-arginine beta-naphthylamide (PA beta N) is 4.6 mu M. (C) 2018 Elsevier Masson SAS. All rights reserved

Causal effects of body mass index on airflow obstruction and forced mid-expiratory flow: a mendelian randomization study taking interactions and age-specific instruments into consideration toward a life course perspective

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18–60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25–75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25–75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25–75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes

Surrogate Models and Mixtures of Experts in Aerodynamic Performance Prediction for Mission Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140436/1/6.2014-2301.pd

Depression trajectories during the COVID-19 pandemic in the high-quality health care setting of Switzerland: the COVCO-Basel cohort

OBJECTIVES: During the pandemic, Switzerland avoided stringent lockdowns and provided funds to stabilize the economy. To assess whether and in what subgroups the pandemic impacted on depressive symptoms in this specific Swiss context, we derived depression trajectories over an extended pandemic period in a Swiss cohort and related them to individuals' sociodemographic characteristics. STUDY DESIGN: This was a population-based cohort study. METHODS: The population-based COVCO-Basel cohort in North-Western Switzerland invited 112,848 adult residents of whom 12,724 participated at baseline. Between July 2020 and December 2021, 6396 participants answered to additional 18 monthly online questionnaires. Depression symptoms were repeatedly measured by the DASS-21 scale. Group-based Trajectory Models methods were applied to identify clusters of similar depression trajectories. Trajectory clusters were characterized descriptively and with a Multinomial response model. RESULTS: Three distinct trajectories were identified. The 'Highly affected' trajectory (13%) had a larger presence of younger and female participants with lower average income, higher levels of past depression, and living alone. A majority of individuals in the 'Unaffected' trajectory (52%) were of medium or high average income, older average age, without previous depression symptoms, and not living alone. The 'Moderately affected' trajectory (35%) had a composition intermediate between the two opposite 'extreme' trajectories. CONCLUSIONS: This study is among few studies investigating depression trajectories up to the time when COVID-19 vaccination was readily available to the entire population. During these 18 months of the pandemic, depressive symptoms increased in a substantial percentage of participants. Economic support, high-quality health care system, and moderate containment measures did not sufficiently protect all population subgroups from adverse, potentially long-term psychological pandemic impacts