An Efficient Protocol for the Palladium-Catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst

Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2-allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and piperazinones has been previously reported by our laboratory. The efficient construction of chiral all-carbon quaternary centers by allylic alkylation was previously achieved with a catalyst derived in situ from zero-valent palladium sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved reaction protocol with broad applicability among different substrate classes in industry-compatible reaction media using loadings of palladium(II) acetate as low as 0.075 mol% and the readily available chiral PHOX ligands. The novel and highly efficient procedure enables facile scale-up of the reaction in an economical and sustainable fashion

nanoparticles production and inclusion in s aureus incubated with polyurethane an electron microscopy analysis

This study shows that submicron/nanoparticles found in bacterial cells (S. aureus) incubated with polyurethane (a material commonly used for prostheses in odontostomatology) are a consequence of biodestruction. The presence of polyurethane nanoparticles into bacterial vesicles suggests that the internalization process occurs through endocytosis. TEM and FIB/SEM are a suitable set of correlated instruments and techniques for this multi facet investigation: polyurethane particles influence the properties of S. aureus from the morpho-functional standpoint that may have undesirable effects on the human body. S. aureus and C. albicans are symbiotic microorganisms; it was observed that C. albicans has a similar interaction with polyurethane and an increment of the biodestruction capacity is expected by its mutual work with S. aureus

Epidemiological Differences between Localized and Nonlocalized Low Back Pain

Study Design. A cross-sectional survey with a longitudinal follow-up. Objectives. The aim of this study was to test the hypothesis that pain, which is localized to the low back, differs epidemiologically from that which occurs simultaneously or close in time to pain at other anatomical sites Summary of Background Data. Low back pain (LBP) often occurs in combination with other regional pain, with which it shares similar psychological and psychosocial risk factors. However, few previous epidemiological studies of LBP have distinguished pain that is confined to the low back from that which occurs as part of a wider distribution of pain. Methods. We analyzed data from CUPID, a cohort study that used baseline and follow-up questionnaires to collect information about musculoskeletal pain, associated disability, and potential risk factors, in 47 occupational groups (office workers, nurses, and others) from 18 countries. Results. Among 12,197 subjects at baseline, 609 (4.9%) reported localized LBP in the past month, and 3820 (31.3%) nonlocalized LBP. Nonlocalized LBP was more frequently associated with sciatica in the past month (48.1% vs. 30.0% of cases), occurred on more days in the past month and past year, was more often disabling for everyday activities (64.1% vs. 47.3% of cases), and had more frequently led to medical consultation and sickness absence from work. It was also more often persistent when participants were followed up after a mean of 14 months (65.6% vs. 54.1% of cases). In adjusted Poisson regression analyses, nonlocalized LBP was differentially associated with risk factors, particularly female sex, older age, and somatizing tendency. There were also marked differences in the relative prevalence of localized and nonlocalized LBP by occupational group. Conclusion. Future epidemiological studies should distinguish where possible between pain that is limited to the low back and LBP that occurs in association with pain at other anatomical locations

Mechanism and Enantioselectivity in Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to β‑Substituted Cyclic Enones: Insights from Computation and Experiment

Enantioselective conjugate additions of arylboronic acids to β-substituted cyclic enones have been previously reported from our laboratories. Air- and moisture-tolerant conditions were achieved with a catalyst derived in situ from palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report a combined experimental and computational investigation on the mechanism, the nature of the active catalyst, the origins of the enantioselectivity, and the stereoelectronic effects of the ligand and the substrates of this transformation. Enantioselectivity is controlled primarily by steric repulsions between the t-Bu group of the chiral ligand and the α-methylene hydrogens of the enone substrate in the enantiodetermining carbopalladation step. Computations indicate that the reaction occurs via formation of a cationic arylpalladium(II) species, and subsequent carbopalladation of the enone olefin forms the key carbon–carbon bond. Studies of nonlinear effects and stoichiometric and catalytic reactions of isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium–ligand complex is the active species in the selectivity-determining step. The addition of water and ammonium hexafluorophosphate synergistically increases the rate of the reaction, corroborating the hypothesis that a cationic palladium species is involved in the reaction pathway. These additives also allow the reaction to be performed at 40 °C and facilitate an expanded substrate scope

Granular time warp objects

A recent trend has shown the relevance of PDES paradigms where simulation objects are no longer seen as fully disjoint entities only interacting via events' scheduling. Particularly, mutual cross-state access (as a form of state sharing) can represent an approach enabling the simplification of the programmer's job. In this article, we present a multi-core oriented Time Warp platform supporting so called granular objects, where cross-state access is transparently enabled jointly with the dynamic clustering (granulation) of objects into groups depending on the volume of mutual state accesses along phases of the model execution. Each group represents an island where activities are sequentially dispatched in timestamp order. Concurrency is still preserved by enabling the optimistic execution of the different islands. Granulated objects do not pay synchronization costs due to mutual causal inconsistencies. Also, the underlying Time Warp platform does not pay memory management (e.g. memory access tracing) overheads to determine that mutual accesses are taking place within a group. Overall, the platform transparently (and dynamically) determines a well-suited granulation of the overall model state, and a corresponding level of concurrency, depending on the actual state access pattern by the simulation code. As far as we know, this is the first study where the problem of clustering Time Warp simulation objects is addressed for the case of in-place cross-object state accesses by the application code, and where dynamic granulation of multiple objects in a larger one is supported in a fully transparent manner. We integrated our proposal in the open source ROOT-Sim platform

High-throughput synthesis provides data for predicting molecular properties and reaction success.

The generation of attractive scaffolds for drug discovery efforts requires the expeditious synthesis of diverse analogues from readily available building blocks. This endeavor necessitates a trade-off between diversity and ease of access and is further complicated by uncertainty about the synthesizability and pharmacokinetic properties of the resulting compounds. Here, we document a platform that leverages photocatalytic N-heterocycle synthesis, high-throughput experimentation, automated purification, and physicochemical assays on 1152 discrete reactions. Together, the data generated allow rational predictions of the synthesizability of stereochemically diverse C-substituted N-saturated heterocycles with deep learning and reveal unexpected trends on the relationship between structure and properties. This study exemplifies how organic chemists can exploit state-of-the-art technologies to markedly increase throughput and confidence in the preparation of drug-like molecules