SEALONE (Safety and Efficacy of Coronary Computed Tomography Angiography with Low Dose in Patients Visiting Emergency Room) trial: study protocol for a randomized controlled trial

Objective Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. Methods The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. Results and Conclusion Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible

Synergistic Activation of Amides and Hydrocarbons for Direct C(sp3)–H Acylation Enabled by Metallaphotoredox Catalysis

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimThe utilizations of omnipresent, thermodynamically stable amides and aliphatic C(sp3)−H bonds for various functionalizations are ongoing challenges in catalysis. In particular, the direct coupling between the two functional groups has not been realized. Here, we report the synergistic activation of the two challenging bonds, the amide C−N and unactivated aliphatic C(sp3)−H, via metallaphotoredox catalysis to directly acylate aliphatic C−H bonds utilizing amides as stable and readily accessible acyl surrogates. N-acylsuccinimides served as efficient acyl reagents for the streamlined synthesis of synthetically useful ketones from simple C(sp3)−H substrates. Detailed mechanistic investigations using both computational and experimental mechanistic studies were performed to construct a detailed and complete catalytic cycle. The origin of the superior reactivity of the N-acylsuccinimides over other more reactive acyl sources such as acyl chlorides was found to be an uncommon reaction pathway which commences with C−H activation prior to oxidative addition of the acyl substrate11sciescopu

Toward fast and accurate machine learning interatomic potentials for atomic layer deposition precursors

Under thin film deposition, when used in conjunction with the semiconductor atomic layer deposition (ALD) method, the choice of precursor determines the properties and quality of the thin film. Organometallic precursors such as alkaline earth metals (Sr and Ba) and group 4 transition metals (Zr and Hf) with cyclopentadienyl and tetrakis (ethylmethylamino) ligands have recently gained attention for their stable deposition within high-temperature windows in the ALD. The design of organometallic precursors with an ab initio molecular dynamics (AIMD) simulations-based approach ensures high accuracy but comes with significant computational costs. In this study, we aim to develop a machine-learning interatomic potential (MLIP) through moment tensor potential (MTP) for fast and accurate potential development of Sr, Ba, Zr, and Hf precursors. To establish the reliable training database for MTP construction, we conducted AIMD simulations on each precursor across a range of temperature settings, resulting in a variety of atomic structures. Constructed MTPs enable efficient utilization of molecular dynamics (MD) simulations as well as calculations that achieve an accuracy that approximates density functional theory (DFT). MTP construction coupled with active learning ensures that the MTP for each precursor is reliable and that databases can be expanded. High prediction accuracy is demonstrated by a mean absolute error (MAE) of less than 0.04 eV/atom in all structures. In addition, generalization performance is confirmed for general structures (structures with the same chemical elements but different proportions) and is extended to cluster structures. The constructed MTP exhibits an MAE of less than 0.15 eV/atom, even for untrained cluster structures. These results demonstrate adequate representation and scalability as a basis for the development of MLIPs capable of atomic simulations of organometallic precursors under various thermodynamic conditions

One-pot bifunctionalization of unactivated alkenes, P(O)-H compounds, and N-methoxypyridinium salts for the construction of β-pyridyl alkylphosphonates

β-Pyridylphosphines consisting of vicinal pyridine and phosphine groups possess soft acceptor properties of phosphines and hard σ-donor features of pyridines. An efficient method for the synthesis of β-pyridyl alkylphosphonates was developed via a three-component reaction between P(O)-H compounds, alkenes and N-methoxypyridinium salts under mild conditions. The reaction is thought to occur by the addition of a phosphonyl radical to the alkene to form alkyl radical intermediate, which goes on to add to the N- N-methoxypyridinium salt. Solvation plays an important role and DFT calculations suggest that the solvation effect is critical in the first step where an alkyl radical intermediate is formed by coupling the phosphonyl radical and the alkene substrate. A plausible mechanism is proposed based on DFT calculations and this novel methodology is applied to a variety of heteroarenium salts and alkene substrates to prepare various synthetically and biologically important β-pyridyl alkylphosphonates. © 2018 the Partner Organisations11sci

Nickel‐Catalyzed Anionic Cross‐Coupling Reaction of Lithium Sulfonimidoyl Alkylidene Carbenoids With Organolithiums

The mechanistic platform for a novel nickel(0)-catalyzed anionic cross-coupling reaction (ACCR) of lithium sulfonimidoyl alkylidene carbenoids (metalloalkenyl sulfoximines) with organometallic reagents is reported herein, affording substituted alkenylmetals and lithium sulfinamides. The Ni-0-catalyzed ACCR of three different types of metalloalkenyl sulfoximines, including acyclic, axially chiral and exocyclic derivatives, with sp(2) organolithiums and sp(2) and sp(3) Grignard reagents has been studied. The ACCR of metalloalkenyl sulfoximines with PhLi in the presence of the Ni-0-catalyst and precatalyst Ni(PPh3)(2)Cl-2 afforded alkenyllithiums, under inversion of configuration at the C atom and complete retention at the S atom. In a combination of experimental and DFT studies, we propose a catalytic cycle of the Ni-0-catalyzed ACCR of lithioalkenyl sulfoximines. Computational studies reveal two distinctive pathways of the ACCR, depending on whether a phosphine or 1,5-cyclooctadiene (COD) is the ligand of the Ni atom. They rectify the underlying importance of forming the key Ni-0-vinylidene intermediate through an indispensable electron-rich Ni-0-center coordinated by phosphine ligands. Fundamentally, we present a mechanistic study in controlling the diastereoselectivity of the alkenyllithium formation via the key lithium sulfinamide coordinated Ni-0-vinylidene complex, which consequently avoids an unselective formation of an alkylidene carbene Ni-complex and ultimately racemic alkenyllithium. T 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinhei

Enantioselective [2+2] Cycloadditions of Cinnamate Esters: Generalizing Lewis Acid Catalysis of Triplet Energy Transfer

© 2019 American Chemical Society.We report the enantioselective [2+2] cycloaddition of simple cinnamate esters, the products of which are useful synthons for the controlled assembly of cyclobutane natural products. This method utilizes a cocatalytic system in which a chiral Lewis acid accelerates the transfer of triplet energy from an excited-state Ir(III) photocatalyst to the cinnamate ester. Computational evidence indicates that the principal role of the Lewis acid cocatalyst is to lower the absolute energies of the substrate frontier molecular orbitals, leading to greater electronic coupling between the sensitizer and substrate and increasing the rate of the energy transfer event. These results suggest Lewis acids can have multiple beneficial effects on triplet sensitization reactions, impacting both the thermodynamic driving force and kinetics of Dexter energy transfer © 2019 American Chemical Societ

Enantioselective [2+2] Cycloadditions of Cinnamate Esters: Generalizing Lewis Acid Catalysis of Triplet Energy Transfer

We report the enantioselective [2+2] cycloaddition of simple cinnamate esters, the products of which are useful synthons for the controlled assembly of cyclobutane natural products. This method utilizes a cocatalytic system in which a chiral Lewis acid accelerates the transfer of triplet energy from an excited-state Ir(III) photocatalyst to the cinnamate ester. Computational evidence indicates that the principal role of the Lewis acid cocatalyst is to lower the absolute energies of the substrate frontier molecular orbitals, leading to greater electronic coupling between the sensitizer and substrate and increasing the rate of the energy transfer event. These results suggest Lewis acids can have multiple beneficial effects on triplet sensitization reactions, impacting both the thermodynamic driving force and kinetics of Dexter energy transfer

Nickel-Catalyzed Anionic Cross-Coupling Reaction of Lithium Sulfonimidoyl Alkylidene Carbenoids With Organolithiums

The mechanistic platform for a novel nickel(0)-catalyzed anionic cross-coupling reaction (ACCR) of lithium sulfonimidoyl alkylidene carbenoids (metalloalkenyl sulfoximines) with organometallic reagents is reported herein, affording substituted alkenylmetals and lithium sulfinamides. The Ni-0-catalyzed ACCR of three different types of metalloalkenyl sulfoximines, including acyclic, axially chiral and exocyclic derivatives, with sp(2) organolithiums and sp(2) and sp(3) Grignard reagents has been studied. The ACCR of metalloalkenyl sulfoximines with PhLi in the presence of the Ni-0-catalyst and precatalyst Ni(PPh3)(2)Cl-2 afforded alkenyllithiums, under inversion of configuration at the C atom and complete retention at the S atom. In a combination of experimental and DFT studies, we propose a catalytic cycle of the Ni-0-catalyzed ACCR of lithioalkenyl sulfoximines. Computational studies reveal two distinctive pathways of the ACCR, depending on whether a phosphine or 1,5-cyclooctadiene (COD) is the ligand of the Ni atom. They rectify the underlying importance of forming the key Ni-0-vinylidene intermediate through an indispensable electron-rich Ni-0-center coordinated by phosphine ligands. Fundamentally, we present a mechanistic study in controlling the diastereoselectivity of the alkenyllithium formation via the key lithium sulfinamide coordinated Ni-0-vinylidene complex, which consequently avoids an unselective formation of an alkylidene carbene Ni-complex and ultimately racemic alkenyllithium. T 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinhei

Room temperature olefination of methane with titanium-carbon multiple bonds

C-H activation of methane followed by dehydrocoupling at room temperature led ultimately to the formation of the olefin H2CCHtBu via the addition of redox-active ligands (L) such as thioxanthone or 2,2′-bipyridine (bipy) to (PNP)TiCHtBu(CH3) (1). Using both of these exogenous ligand systems, we could trap the titanium fragment via an insertion reaction with these two substrates to afford species of the type (PNP)Ti(L)(LH). A combination of computational and isotopic labeling studies reveals that the L ligand promotes the C-C bond forming step by migration of the methyl moiety in 1 to the α-alkylidene carbon by producing a Ti(iii) species (PNP)Ti{CH(CH3)tBu}(L). In the case of L = thioxanthone, β-hydrogen abstraction gives an olefin, whereas with 2,2′-bipyridine β-hydride elimination and migratory insertion lead to (PNP)Ti(L)(LH). These redox-active ligands play two important roles: (i) they accept an electron from the Ti-alkylidene fragment to allow the methyl to approach the alkylidene and (ii) they serve as traps of a hydrogen atom resulting from olefin elimination. These systems represent the first homogeneous models that can activate methane and selectively dehydrocouple it with a carbene to produce an olefin at room temperature. © 2018 The Royal Society of Chemistry11sciescopu

Ni-Catalyzed Intermolecular C(sp3)-H Amidation Tuned by Bidentate Directing Groups

We disclose herein a directing group-assisted nickel-catalyzed intermolecular C(sp3)-H amidation using organic azides as nitrene precursors. With the installation of an electronically tailored directing group, enhanced amidation efficiency was achieved. A series of experimental and computational studies suggested that a putative nickel(III)-nitrenoid species is a key intermediate in the C-N bond-forming process.11Nsciescopu