Asymmetric Hydrogenation of 1-aryl substituted-3,4-Dihydroisoquinolines with Iridium Catalysts Bearing Different Phosphorus-Based Ligands

Starting from the chiral 5,6,7,8-tetrahydroquinolin-8-ol core, a series of amino-phosphorusbased ligands was realized. The so-obtained amino-phosphine ligand (L1), amino-phosphinite (L2) and amino-phosphite (L3) were evaluated in iridium complexes together with the heterobiaryl diphosphines tetraMe-BITIOP (L4), Diophep (L5) and L6 and L7 ligands, characterized by mixed chirality. Their catalytic performance in the asymmetric hydrogenation (AH) of the model substrate 6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinoline 1a led us to identify Ir-L4 and Ir-L5 catalysts as the most eective. The application of these catalytic systems to a library of dierently substituted 1-aryl-3,4-dihydroisoquinolines aorded the corresponding products with variable enantioselective levels. The 4-nitrophenyl derivative 3b was obtained in a complete conversion and with an excellent 94% e.e. using Ir-L4, and a good 76% e.e. was achieved in the reduction of 2-nitrophenyl derivative 6a using Ir-L5

Morphometric parameters of cardiac implantable electronic device (CIED) pocket walls observed on device replacement

Background: The final stage of a conventional de-novo cardiac implantable electronic device (CIED) implantation procedure with transvenous lead insertion involves the formation of a pocket by tissue separation superficial to the pectoralis major muscle in the right or left infraclavicular region, where the device is subsequently placed. Over time, a scar “capsule” is formed around the CIED as a result of normal biological remodelling. Materials and methods: The purpose of this study was to analyse the structure and present the variations of CIED capsules observed during device replacement. The nature and extent of this local tissue remodelling, which had occurred from the time of device implantation to its replacement in 2016 (10 ± 3.1 years), was analysed in 100 patients (mean age 77.1 ± 14.5 years), including 45 women and 55 men. Results: The most prevalent types of “capsules” (70% of cases) were those with similar thickness of both walls or a slightly thicker posterior (< 1.0 mm) than anterior wall (< 0.5 mm). The second most common capsule type (23% of cases) was characterised by a significantly thicker posterior wall of scar tissue (> 1.0 mm). The third group of capsules was characterised by various degrees of wall calcification (7% of cases). Conclusions: The extent and nature of scar tissue structure in the CIED pocket walls seem to correlate with the relative position of cardiac lead loops with respect to the device itself; where the more extensive scarring is likely to result from pocket wall irritation in the capsule formation phase due to lead movements underneath the device. The group of cases with calcified capsules was characterised by “old” device pockets (> 13 years) and the oldest population (patients in their 80s and 90s)

On the relation between carbonyl stretching frequencies and the donor power of chelating diphosphines in nickel dicarbonyl complexes

The relation between spectroscopic observables and the detailed metal- ligand bonding features in chelation complexes is addressed using both experimental and state-of-the-art theoretical and computational methods. We synthesized and characterized a set of six nickel dicarbonyl complexes of general formula [Ni(CO)(2)(PP)], where PP is an atropoisomeric chelating diphosphine ligand. The analysis of the obtained experimental data and the basicity and oxidative potentials of the free ligands suggests a close relation between the donor ability of the chelating ligand and the carbonyl stretching frequencies observed in the complexes. We then use theory to unravel the detailed mechanisms of chelation-bond formation in terms of partial charge flows between the molecular orbitals of the fragments. By extending the promising, recently published natural orbitals for chemical valence/ charge displacement (NOCV/CD) analysis scheme we provide a thorough, quantitative description of the several charge fluxes following the metal-ligand bond formation and demonstrate that the carbonyl stretching frequencies in the considered complexes selectively respond to the sigma-donation charge flow from the phosphorus lone pairs of the ligands, with the frequency shift being in quantitative correlation with the extent of the ligand-to-metal charge transfer

In-hospital complications after invasive strategy for the management of Non STEMI: women fare as well as men

<p>Abstract</p> <p>Background</p> <p>To analyze the in-hospital complication rate in women suffering from non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) compared to men.</p> <p>Methods</p> <p>The files of 479 consecutive patients (133 women and 346 men) suffering from a Non STEMI (Non ST-segment elevation myocardial infarction) between the January 1^st2006 and March 21^st2009 were retrospectively analyzed with special attention to every single complication occurring during hospital stay. Data were analyzed using nonparametric tests and are reported as median unless otherwise specified. A p value < .05 was considered significant.</p> <p>Results</p> <p>As compared to men, women were significantly older (75.8 <it>vs</it>. 65.2 years; p < .005). All cardiovascular risk factors but tobacco and hypertension were similar between the groups: men were noticeably more often smoker (p < .0001) and women more hypertensive (p < .005). No difference was noticed for pre-hospital cardiovascular drug treatment. However women were slightly more severe at entry (more Killip class IV; p = .0023; higher GRACE score for in-hospital death - p = .008 and CRUSADE score for bleeding - p < .0001). All the patients underwent PCI of the infarct-related artery after 24 or 48 hrs post admission without sex-related difference either for timing of PCI or primary success rate. During hospitalization, 130 complications were recorded. Though the event rate was slightly higher in women (30% <it>vs</it>. 26% - p = NS), no single event was significantly gender related. The logistic regression identified age and CRP concentration as the only predictive variables in the whole group. After splitting for genders, these parameters were still predictive of events in men. In women however, CRP was the only one with a borderline p value.</p> <p>Conclusions</p> <p>Our study does not support any gender difference for in-hospital adverse events in patients treated invasively for an acute coronary syndrome without ST-segment elevation and elevated troponin.</p

The Rotterdam Study: objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in the Netherlands. The study targets cardiovascular, neurological, ophthalmological and endocrine diseases. As of 2008 about 15,000 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in some 600 research articles and reports (see http://www.epib.nl/rotterdamstudy). This article gives the reasons for the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

The Rotterdam Study: 2010 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in close to a 1,000 research articles and reports (see www.epib.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

Diastereoselectivity and catalytic activity in ruthenium complexes chiral at the metal centre

Cis-RuCl2(diphosphine)(CAMPY) complexes, chiral at the metal centre with matching or mismatching chiralities between diphosphine and CAMPY were prepared and the configuration at the metal was determined in solution by a complete set of NMR investigations; CAMPY is (R)-( ) or (S)-(\ufe)-8-amino- 5,6,7,8-tetrahydroquinoline. The complexes were used in ATH reactions of different aryl ketones with 2- propanol as hydrogen source. The effects of the chirality at the metal were studied and enantiomeric excesses up to 99% were obtained

Enantioselective transfer hydrogenation of aryl ketones: synthesis and 2D-NMR characterization of new 8-amino-5,6,7,8-tetrahydroquinoline Ru(II)-complexes

Chiral (R)-(-) and (S)-(+)-8-amino-5,6,7,8-tetrahydroquinoline, hereafter defined (R)-CAMPY and (S)-CAMPY, have proved to be valuable chiral ligands in Ru(II) precatalysts for the reduction of prochiral ketones by asymmetric hydrogen transfer AHT. These ligands bear chiral information on an alkyl ring fused to a pyridine and therefore have a flat nature, characterized by a high conformational rigidity. It represent the first application in AHT of a member of a family of ancillary ligands already known as starting material for medicinal compouds. The reaction with [RuCl2PPh3] furnished the (OC-6-14)-[RuCl2(PPh3)2(CAMPY)] which evolved to (OC-6-42-C)- [RuCl2(PPh3)2(CAMPY)] in refluxing toluene. The absence of a suitable crystal for X-ray structure was easily overcame by a combination of routines 2D-NMR experiments based on an unprecedent 4-bond P-H coupling. The formation of (OC-6-42-C)- [RuCl2(PPh3)2(CAMPY)] is totally stereoselective at the chiral metal center; the same behavior is followed when triphenyl phosphines are displaced by chelating diphosphines like Ph2P(CH2)4PPh2 (DPPB) and Ph2P(CH2)3PPh2 (DPPP). The flat and rigid nature of CAMPY alone gave catalyst able to reduce acetophenone with moderate e.e.; substitution of triphenylphosphines in the complex with an achiral chelating diphosphines produce Ru-catalysts witch gave enantioselectivities up to 96%

8-Amino-5,6,7,8-Tetrahydroquinolines as Ligands in Iridium(III) Catalysts for the Reduction of Aryl Ketones by asymmetric transfer hydrogenation (ATH)

Recently, it has been demonstrated the possibility to use iridium complexes as a valid alternative to the use of classical ruthenium systems.1 Aqua iridium(III) complexes with 8-amino-5,6,7,8- tetrahydroquinolines, CAMPY L1 and its derivatives as chiral ligands proved to be very efficient catalysts in the reduction of a wide range of prochiral aryl ketones, revealing a variety of behaviours in terms of reaction rate and stereoselectivity. Screening was carried out for the reduction of different types of aryl ketones and three hydrogen donors were evaluated: A deep variety of behaviours emerged by changing reaction conditions, stressing the matching between the substrates and the ligands used in the metal complexes. In particular the presence of HCOOH as hydrogen donor played an important role on the stereoselctivity of the catalysts. ATH reactions on \u3b2-lactam precursors led to interesting results achieving very high