Formation of CNHC∧Calkyl and CNHC∧Caryl κ2-Chelate Complexes through Competitive sp3- and sp2-CH Activations: An Experimental and Computational Study.

Depending on the chelate ring present, cyclometalated complexes are useful catalysts for various reactions. The reactivity of IrIII and RhIII NHC complexes bearing aliphatic or aromatic N,N'-substituents and thus featuring various metalation sites toward cyclometalation has been investigated. The RhIII complex bearing an N-mesityl-N'-benzyl-NHC does not participate in any cyclometalation, while the IrIII complex reacts under metalation of an ortho-methyl group of the Mes substituent to give complex [3] with a six-membered chelate ring. The RhIII and IrIII complexes bearing an N-o-tolyl,N-benzyl-NHC undergo sp2-CH activation to yield the cyclometalated complexes [4] and [5] featuring a five-membered CNHC∧C chelate ring. Density functional theory (DFT) studies corroborated the experimental findings.

Unravelling the Roles of Solvophobic Effects and π⋠⋠⋠π Stacking Interactions in the Formation of [2]Catenanes Featuring Di-(N-Heterocyclic Carbene) Building Blocks.

A series of [2]catenanes has been prepared from di-NHC building blocks by utilizing solvophobic effects and/or π⋅⋅⋅π stacking interactions. The dinickel naphthobiscarbene complex syn-[1] and the kinked biphenyl-bridged bipyridyl ligand L2 yield the [2]catenane [2-IL](OTf)4 by self-assembly. Solvophobic effects are pivotal for the formation of the interlocked species. Substitution of the biphenyl-linker in L2 for a pyromellitic diimide group gave ligand L3 , which yielded in combination with syn-[1] the [2]catenane [3-IL](OTf)4 . This assembly exhibits enhanced stability in diluted solution, aided by additional π⋅⋅⋅π stacking interactions. The π⋅⋅⋅π stacking was augmented by the introduction of a pyrene bridge between two NHC donors in ligand L4 . Di-NHC precursor H2 -L4 (PF6 )2 reacts with Ag2 O to give the [Ag2 L4 2 ]2 [2]catenane [4-IL](PF6 )4 , which shows strong π⋅⋅⋅π stacking interactions between the pyrene groups. This assembly was readily converted into the [Au2 L4 2 ]2 gold species [5-IL](PF6 )4 , which exhibits exceptional stability based on the strong π⋅⋅⋅π stacking interactions and the enhanced stability of the Au-CNHC bonds.

Trinuclear PdII Complexes with a C3 -Symmetric Triethynylbenzene-Based Tris-NHC Ligand: Catalytic Benefits.

A new C3 -symmetric tris-imidazolium tribromide salt 3, featuring 1,3,5-substituted triethynylbenzene, was used for the preparation of a trinuclear PdII pyridine-enhanced precatalyst preparation stabilization and initiation-type (PEPPSI) complex by triple C2 deprotonation followed by the addition of PdCl2 . Trinuclear PdII complex possessing a combination of NHC and PPh3 ligands has also been synthesized. The corresponding mononuclear palladium(II) complexes have also been synthesized for the comparison purpose. All these complexes have been characterized by using NMR spectroscopy and ESI mass spectrometry. The molecular structure of the trinuclear palladium(II) complex bearing mixed carbene and pyridine donor ligands has been established by using single crystal XRD. All the palladium(II) complexes have been used as pre-catalysts, which gave good to excellent yields in intermolecular α-arylation of 1-methyl-2-oxindole and Sonogashira coupling reaction. Catalytic studies indicate an enhanced activity of the trinuclear PdII complex in comparison to the corresponding mononuclear PdII complex for both catalytic transformations. The better performance of the trinuclear complex has also been further supported by preliminary electrochemical measurements. A negative mercury poison test was observed for both the aforementioned catalyses and therefore, it is likely that these organic transformations proceed homogeneously.

Organometallic Borromean Rings and [2]Catenanes Featuring Di-NHC Ligands.

We report herein a series of organometallic Borromean rings (BRs) and [2]catenanes prepared from benzobiscarbene ligands. The reaction of dinickel complexes of the benzobiscarbenes 1 a-1 c with a thiazolothiazole bridged bipyridyl ligand L2 led by self-assembly to a series of organometallic BRs. Solvophobic effects played a crucial role in the formation and stability of the interlocked species. The stability of BRs is related to the N-alkyl substituents at the precursors 1 a-1 c, where longer alkyl substitutes improve stability and inter-ring interactions. Solvophobic effects are also important for the stability of [2]catenanes prepared from 1 a-1 c and a flexible bipyridyl ligand L3 . In solution, an equilibrium between the [2]catenanes and their macrocyclic building blocks was observed. High proportions of [2]catenanes were obtained in concentrated solutions or polar solvents. The proportion of [2]catenanes in solution could be further enhanced by lengthening of the N-alkyl substitutes.

Qualitative evaluation of postdoctoral trainee and faculty advisor experiences within a research-intensive school of pharmacy.

BACKGROUND: Postdoctoral trainees play a vital role in securing grant funding, building alliances, and mentoring graduate students under the guidance of a mentor who can help develop their intellectual independence. However, the experiences of postdoctoral trainees, particularly within health professions schools, is largely unexplored. The purpose of this study was to investigate the experiences of postdoctoral trainees and faculty advisors at a public four-year school of pharmacy and identify areas of opportunity to improve postdoctoral training. METHODS: Focus groups and interviews were conducted to elicit participants' experiences, perceptions, and suggestions for improvement. Stakeholder groups included postdoctoral trainees and faculty who serve as postdoctoral advisors. Thematic coding was used to identify semantic themes, and summaries of participant perceptions were generated. Results were mapped to the identity-trajectory framework. RESULTS: Participants described various experiences related to intellectual growth, networking opportunities, and institutional support. In addition, participant agency was critical for developing career goals and navigating transitions. COVID-19 introduced unique challenges associated with transitioning to remote work and managing goals/motivation. Areas of opportunity were identified, such as improving infrastructure, enhancing mentoring, and enhancing communication. CONCLUSION: Postdoctoral trainees play a critical role in the success of academic institutions. Scholarly endeavors that explore postdoctoral experiences, specifically those utilizing qualitative methods, can help pharmacy education better understand and meet the needs of postdoctoral trainees and faculty advisors. This study provides insight into the experiences of postdoctoral scholars and provides evidence for improving these training programs in schools of pharmacy.

Photon-counting detector CT improves quality of arterial phase abdominal scans: A head-to-head comparison with energy-integrating CT.

PURPOSE: Photon-counting detector (PCD)-CT is expected to have a substantial impact on oncologic abdominal imaging. We compared subjective and objective image quality between PCD-CT and conventional energy-integrating detector (EID-)CT arterial phase abdominal scans. METHODS: This study included 84 patients undergoing both types of abdominal CT. EID-CT scans were acquired with a tube voltage of 100 kVp. With PCD-CT, acquired with 120-kVp, we reconstructed polychromatic T3D images and virtual monoenergetic images (VMIs) in 10-keV intervals from 40 to 90 keV. Quantitative image analysis included noise and contrast-to-noise ratio (CNR) of hepatic vessels, kidney cortex, and hypervascular liver lesions to liver parenchyma. Three raters used a 5-point Likert scale for qualitative image analysis of image noise and contrast, lesion conspicuity, and overall image quality. Radiation dose exposure (CT dose index) was compared between the two CT types. RESULTS: Mean CT dose index and effective dose were respectively 18 % and 26 % lower with PCD-CT versus EID-CT. Compared with EID-CT, CNRs of kidney cortex and vessel to liver parenchyma were significantly higher in PCD-CT VMIs at energies ≤ 60 keV and in polychromatic T3D images (p < 0.004). Overall image quality of PCD-CT VMIs at 50 and 60 keV was rated as significantly better (p < 0.01) than the EID-CT images (inter-reader agreement alpha = 0.80). Lesion conspicuity was significantly better in low-keV VMIs (p < 0.03) and worse in > 70-keV VMIs. CONCLUSIONS: With low-keV VMI, PCD-CT yields significantly improved objective and subjective quality of arterial phase oncological imaging compared with EID-CT. This advantage may translate into higher diagnostic confidence and lower radiation dose protocols.

N-heterocyclic carbene-stabilized metal nanoparticles within porous organic cages for catalytic application.

Tuning the surface-embellishing ligands of metal nanoparticles (NPs) is a powerful strategy to modulate their morphology and surface electronic and functional features, impacting their catalytic activity and selectivity. In this work, we report the design and synthesis of a polytriazolium organic cage PIC-T, capable of stabilizing PdNPs within its discrete cavity. The obtained material (denoted Pd@PCC-T) is highly durable and monodispersed with narrow particle-size distribution of 2.06 ± 0.02 nm, exhibiting excellent catalytic performance and recyclability in the Sonogashira coupling and tandem reaction to synthesize benzofuran derivatives. Further investigation indicates that the modulation of N-heterocyclic carbene sites embedded in the organic cage has an impact on NPs' catalytic efficiency, thus providing a novel methodology to design superior NP catalysts.

Palladium-Catalyzed Three-Component Dearomatization/Sulfonylation Cascade.

The diastereoselective synthesis of sulfonylated indolines is reported. A palladium-catalyzed dearomative sulfination of (aza)indole-tethered aryl iodides generates reactive benzylic sulfinates. These intermediates react with electrophiles in a one-pot, two-step process to generate sulfonylated products in good yields and excellent diastereoselectivity. This three-component sequence demonstrates good scalability and can be applied toward the synthesis of sulfonamides. Additionally, further derivatizations of aryl iodide containing products furnish spiro- and alkynylated indoline products.

Synthesis of N-Heterocyclic Carbenes and Their Complexes by Chloronium Ion Abstraction from 2-Chloroazolium Salts Using Electron-Rich Phosphines.

N-Heterocyclic carbenes (NHCs) are commonly prepared by deprotonation of azolium salts using strong anionic bases. This reaction is often unselective, yielding alkali metal NHC complexes or dimerized NHCs. Alternatively, free NHCs are obtained by the dechlorination of 2-chloroazolium salts using electron-rich phosphines. PPh3 , PCy3 , and PtBu3 are unsuitable for Cl+ abstraction, while the sterically encumbered tris(1,3-tert-butylimidazolidin-2-ylidenamino)phosphine 1 selectively removes Cl+ from 2-chloroazolium salts. Since bulky 1 does not bind to metal complexes, it was used for the preparation of NHC complexes via in situ Cl+ abstraction from 2-chloroazolium salts. The dechlorination was employed for the site-selective monometallation with IrI , IrIII , RhI , RhIII , and RuII of a bis-NHC precursor composed of a 2-chlorobenzimidazolium and a 2-chlorobenzimidazole group, followed by the preparation of the heterobimetallic IrIII /PdII complex [18](BF4 )2 by a dechlorination/oxidative addition reaction sequence.

Natural language processing of radiology reports to investigate the effects of the COVID-19 pandemic on the incidence and age distribution of fractures.

OBJECTIVE: During the COVID-19 pandemic, the number of patients presenting in hospitals because of emergency conditions decreased. Radiology is thus confronted with the effects of the pandemic. The aim of this study was to use natural language processing (NLP) to automatically analyze the number and distribution of fractures during the pandemic and in the 5 years before the pandemic. MATERIALS AND METHODS: We used a pre-trained commercially available NLP engine to automatically categorize 5397 radiological reports of radiographs (hand/wrist, elbow, shoulder, ankle, knee, pelvis/hip) within a 6-week period from March to April in 2015-2020 into "fracture affirmed" or "fracture not affirmed." The NLP engine achieved an F1 score of 0.81 compared to human annotators. RESULTS: In 2020, we found a significant decrease of fractures in general (p < 0.001); the average number of fractures in 2015-2019 was 295, whereas it was 233 in 2020. In children and adolescents (p < 0.001), and in adults up to 65 years (p = 0.006), significantly fewer fractures were reported in 2020. The number of fractures in the elderly did not change (p = 0.15). The number of hand/wrist fractures (p < 0.001) and fractures of the elbow (p < 0.001) was significantly lower in 2020 compared with the average in the years 2015-2019. CONCLUSION: NLP can be used to identify relevant changes in the number of pathologies as shown here for the use case fracture detection. This may trigger root cause analysis and enable automated real-time monitoring in radiology.

The use of a cognitive aid app supports guideline-conforming cardiopulmonary resuscitations: A randomized study in a high-fidelity simulation.

AIM: Cardiac arrests require fast, well-timed, and well-coordinated interventions delivered by several staff members. We evaluated a cognitive aid that works as an attentional aid to support specifically the timing and coordination of these interventions. We report the results of an experimental, simulation-based evaluation of the tablet-based cognitive aid in performing guideline-conforming cardiopulmonary resuscitation. METHODS: In a parallel group design, emergency teams (one qualified emergency physician as team leader and one qualified nurse) were randomly assigned to the cognitive aid application (CA App) group or the no application (No App) group and then participated in a simulated scenario of a cardiac arrest. The primary outcome was a cardiopulmonary resuscitation performance score ranging from zero to two for each team based on the videotaped scenarios in relation to twelve performance variables derived from the European Resuscitation Guidelines. As a secondary outcome, we measured the participants' subjective workload. RESULTS: A total of 67 teams participated. The CA App group (n = 32 teams) showed significantly better cardiopulmonary resuscitation performance than the No App group (n = 31 teams; mean difference = 0.23, 95 %CI = 0.08 to 0.38, p = 0.002, d = 0.83). The CA App group team leaders indicated significantly less mental and physical demand and less effort to achieve their performance compared to the No App group team leaders. CONCLUSIONS: Among well-trained in-hospital emergency teams, the cognitive aid could improve cardiopulmonary resuscitation coordination performance and decrease mental workload.

An "All-in-One" Synthetic Strategy for Linear Metalla[4]Catenanes.

One fascinating and challenging synthetic target in the field of mechanically interlocked molecules is the family of linear [4]catenanes, which are topologically identical to the logo of automobile maker Audi. Herein, we report an "all-in-one" synthetic strategy for the synthesis of linear metalla[n]catenanes (n = 2-4) by the coordination-driven self-assembly of Cp*Rh-based (Cp* = η5-pentamethylcyclopentadienyl) organometallic rectangle π-donors and tetracationic organic cyclophane π-acceptors. We selected the pyrenyl group as the π-donor unit, leading to homogeneous metalla[2]catenanes and cyclic metalla[3]catenanes via π-stacking interactions. By taking advantage of the strong electrostatic interactions between π-donor units and π-acceptor units, a heterogeneous metalla[2]catenanes and linear metalla[3]catenanes, respectively, could be obtained by the simple stirring of homogeneous metalla[2]catenanes with a suitable tetracationic cyclophane. On this basis, this "all-in-one" synthetic strategy was further used to realize a quantitative one-step synthesis of a linear metalla[4]catenanes via the self-assembly of cyclic metalla[3]catenanes and tetracationic cyclophanes. All heterogeneous metalla[n]catenanes (n = 2-4) were fully characterized by single-crystal X-ray analysis, NMR spectroscopy and electrospray ionization mass spectrometry.

Preparation of Complexes Bearing N-Alkylated, Anionic or Protic CAACs Through Oxidative Addition of 2-Halogenoindole Derivatives.

CAAC precursors 2-chloro-3,3-dimethylindole 1 and 2-chloro-1-ethyl-3,3-dimethylindolium tetrafluoroborate 2BF4 have been prepared and oxidatively added to [M(PPh3 )4 ] (M=Pd, Pt). Salt 2BF4 reacts with [Pd(PPh3 )4 ] in toluene at 25 °C over 4 days to yield complex cis-[3]BF4 featuring an N-ethyl substituted CAAC, two cis-arranged phosphines and a chloro ligand. Compound trans-[3]BF4 was obtained from the same reaction at 80 °C over 1 day. Salt 2BF4 reacts with [Pt(PPh3 )4 ] to give cis-[4]BF4 . The neutral indole derivative 1 adds oxidatively to [Pt(PPh3 )4 ] to give trans-[5] featuring a CAAC ligand with an unsubstituted ring-nitrogen atom. This nitrogen atom has been protonated with py⋅HBF4 to give trans-[6]BF4 bearing a protic CAAC ligand. The PdII complex trans-[7]BF4 bearing a protic CAAC ligand was obtained in a one-pot reaction from 1 and [Pd(PPh3 )4 ] in the presence of py⋅HBF4 .

Chemoselective synthesis of heterobimetallic bis-NHC complexes.

Bis-NHC precursors composed of an azolium and a 2-halogenoazole group connected by different linkers have been site-selectively metallated to give heterobimetallic complexes from a single-frame bis-NHC ligand. The azolium group reacts with a base and oxidized metal centers to give NHC complexes with no participation of the halogenoazole, while the halogenoazole reacts in an oxidative addition with low-valent transition metals to give azolato complexes with no participation of the azolium group.

Synthesis of IrIII Hydrido Complexes by Oxidative Addition of Halogenated Theophylline and Adenine Derivatives.

The IrIII hydrido complexes [1] and [2] have been synthesized by the regioselective oxidative addition of the N7-H bond of 8-halogenotheophyllines to [IrCl(coe)2]2 in the presence of PPh3. The use of dppf in this reaction yielded the bimetallic IrIII/FeII hydrido complexes [3] and [4]. X-ray diffraction studies confirmed that complexes [1]-[4] feature a theophyllinato ligand coordinated to the metal center in the rarely observed, chelating fashion via the N7 and O1 atoms. In addition, 8-bromoadenine reacts with [IrCl(coe)2]2 in the presence of PPh3 to form the IrIII hydrido complex [5] which features one anionic 8-bromoadeninato and one neutral 8-bromoadenine ligand linked by an intramolecular hydrogen bond. Complex [5] was characterized by high-resolution mass spectrometry and an X-ray diffraction analysis but could not be analyzed by nuclear magnetic resonance spectroscopy because of its low solubility.

Template-Controlled Synthesis of Polyimidazolium Salts by Multiple [2+2] Cycloaddition Reactions.

The tetrakisimidazolium salt H4 -2(Br)4 , featuring a central benzene linker and 1,2,4,5-(nBu-imidazolium-Ph-CH=CH-) substituents reacts with Ag2 O in the presence of AgBF4 to yield the tetranuclear, oktakis-NHC assembly [3](BF4 )4 . Cation [3]4+ features four pairs of olefins from the two tetrakis-NHC ligands perfectly arranged for a subsequent [2+2] cycloaddition. Irradiation of [3](BF4 )4 with a high pressure Hg lamp connects the two tetra-NHC ligands through four cyclobutane linkers to give compound [4](BF4 )4 . Removal of the template metals yields the novel oktakisimidazolium salt H8 -5(BF4 )8 . The tetrakisimidazolium salt H4 -2(BF4 )4 and the oktakisimidazolium salt H8 -5(BF4 )8 have been used as multivalent anion receptors and their anion binding properties towards six different anions have been compared.

Supramolecular-induced regiocontrol over the photochemical [4 + 4] cyclodimerization of NHC- or azole-substituted anthracenes.

Thanks to the impressive control that microenvironments within enzymes can have over substrates, many biological reactions occur with high regio- and stereoselectivity. However, comparable regio- and stereoselectivity is extremely difficult to achieve for many types of reactions, particularly photochemical cycloaddition reactions in homogeneous solutions. Here, we describe a supramolecular templating strategy that enables photochemical [4 + 4] cycloaddition of 2,6-difunctionalized anthracenes with unique regio- and stereoselectivity and reactivity using a concept known as the supramolecular approach. The reaction of 2,6-azolium substituted anthracenes H4-L(PF6)2 (L = 1a-1c) with Ag2O yielded complexes anti-[Ag2 L 2](PF6)4 featuring an antiparallel orientation of the anthracene groups. Irradiation of complexes anti-[Ag2 L 2](PF6)4 proceeded under [4 + 4] cycloaddition linking the two anthracene moieties to give cyclodimers anti-[Ag2(2)](PF6)2. Reaction of 2,6-azole substituted anthracenes with a dinuclear complex [Cl-Au-NHC-NHC-Au-Cl] yields tetranuclear assemblies with the anthracene moieties oriented in syn-fashion. Irradiation and demetallation gives a [4 + 4] syn-photodimer of two anthracenes. The stereoselectivity of the [4 + 4] cycloaddition between two anthracene moieties is determined by their orientation in the metallosupramolecular assemblies.

Strategy for the Construction of Diverse Poly-NHC-Derived Assemblies and Their Photoinduced Transformations.

A series of supramolecular assemblies of types [Ag8 (L)4 ](PF6 )8 and [Ag4 (L)2 ](PF6 )4 , obtained from the tetraphenylethylene (TPE) bridged tetrakis(1,2,4-triazolium) salts H4 -L(PF6 )4 and AgI ions, is described. The assembly type obtained dependends on the N-wingtip substituents of H4 -L(PF6 )4 . Changes in the lengths of the N4-wingtip substituents enables controlled formation of assemblies with either [Ag4 (L)2 ](PF6 )4 or [Ag8 (L)4 ](PF6 )8 stoichiometry. The molecular structures of selected [Ag8 (L)4 ](PF6 )8 and [Ag4 (L)2 ](PF6 )4 assemblies were determined by X-ray diffraction analyses. While H4 -L(PF6 )4 does not exhibit fluorescence in solution, their tetra-NHC (NHC=N-heterocyclic carbene) assemblies do upon NHC-metal coordination. Upon irradiation, all assemblies undergo a light-induced, supramolecule-to-supramolecule structural transformation by an oxidative photocyclization involving phenyl groups of the TPE core, resulting in a significant change of the luminescence properties.

C3 -Symmetric Assemblies from Trigonal Polycarbene Ligands and MI Ions for the Synthesis of Three-Dimensional Polyimidazolium Cations.

Metallosupramolecular poly-NHC-metal assemblies were prepared from trigonal hexakis (H6 -1 a(PF6 )6 and H6 -1 b(PF6 )6 ) or nonakis (H9 -3(BF4 )9 ) imidazolium salts and Ag2 O. Complexes [Ag6 (1 a)2 ](PF6 )6 and [Ag6 (1 b)2 ](PF6 )6 are built from six Ag+ ions sandwiched between two trigonal hexacarbene ligands with an inner and an outer NHC donor in each of the three ligand arms. The metal atoms are arranged in two triangles. The hexakis-NHC ligands bear cinnamic ester groups at the outlying NHC donors, used in postsynthetic [2+2] cycloaddition reactions linking two hexakis-NHC ligands by three cyclobutane units to give complexes [Ag6 (2 a)](PF6 )6 and [Ag6 (2 b)](PF6 )6 bearing a dodecacarbene ligand. From the related nonakisimidazolium salt H9 -3(BF4 )9 , complex [Ag9 (4)](BF4 )9 bearing an octadecacarbene ligand was obtained. Removal of the template metals yielded very large, stable, polyimidazolium cations with 12 or 18 internal imidazolium groups.

Synthesis, Characterization, and Properties of Tetraphenylethylene-Based Tetrakis-NHC Ligands and Their Metal Complexes.

The development of highly emissive dinuclear AgI or AuI complexes [M2 L](PF6 )2 (L=2 a, 2 b; M=Ag, Au) derived from tetraphenylethylene (TPE)-based tetrabenzimidazolin-2-ylidene ligands is reported. The new complexes exhibit a remarkable fluorescence enhancement compared to their parent benzimidazolium salts. The quantum yield (ΦF ) value for salt H4 -2 a(PF6 )4 in dilute solution (c=10-5 m) was found to be less than 1 %, whereas its metal complexes show ΦF values up to 55 % at similar solution concentration. This observation can be attributed to the rigidification of the TPE skeleton upon metalation resulting in a restriction of the intramolecular rotation of the phenyl groups. Functionalization of the complexes [M2 2 b](PF6 )2 (M=Ag, Au) with terminal coumarin groups and subsequent photoirradiation yielded the complexes [M2 3 b](PF6 )2 (M=Ag, Au) bearing a new type of ligand with an unaffected TPE moiety.