Pharyngeal electrical stimulation for neurogenic dysphagia following stroke, traumatic brain injury or other causes: Main results from the PHADER cohort study

BackgroundNeurogenic dysphagia is common and has no definitive treatment. We assessed whether pharyngeal electrical stimulation (PES) is associated with reduced dysphagia.MethodsThe PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia European Registry (PHADER) was a prospective single-arm observational cohort study. Participants were recruited with neurogenic dysphagia (comprising five groups – stroke not needing ventilation; stroke needing ventilation; ventilation acquired; traumatic brain injury; other neurological causes). PES was administered once daily for three days. The primary outcome was the validated dysphagia severity rating scale (DSRS, score best-worst 0–12) at 3 months.FindingsOf 255 enrolled patients from 14 centres in Austria, Germany and UK, 10 failed screening. At baseline, mean (standard deviation) or median [interquartile range]: age 68 (14) years, male 71%, DSRS 11·4 (1·7), time from onset to treatment 32 [44] days; age, time and DSRS differed between diagnostic groups. Insertion of PES catheters was successfully inserted in 239/245 (98%) participants, and was typically easy taking 11·8 min. 9 participants withdrew before the end of treatment. DSRS improved significantly in all dysphagia groups, difference in means (95% confidence intervals, CI) from 0 to 3 months: stroke (n = 79) –6·7 (–7·8, –5·5), ventilated stroke (n = 98) –6·5 (–7·6, –5·5); ventilation acquired (n = 35) –6·6 (–8·4, –4·8); traumatic brain injury (n = 24) -4·5 (–6·6, –2·4). The results for DSRS were mirrored for instrumentally assessed penetration aspiration scale scores. DSRS improved in both supratentorial and infratentorial stroke, with no difference between them (p = 0·32). In previously ventilated participants with tracheotomy, DSRS improved more in participants who could be decannulated (n = 66) –7·5 (–8·6, –6·5) versus not decannulated (n = 33) –2·1 (–3·2, –1·0) (

Arene–Ruthenium(II) and −Iridium(III) Complexes with “Click”-Based Pyridyl-triazoles, Bis-triazoles, and Chelating Abnormal Carbenes: Applications in Catalytic Transfer Hydrogenation of Nitrobenzene

The complexes [(Cym)­Ru­(<b>L</b>)­Cl]­PF₆, <b>2</b>–<b>4</b>, and [Cp*Ir­(<b>L</b>)­Cl]­PF₆, <b>6</b>–<b>8</b> (Cym = <i>p</i>-cymene, Cp* = pentamethylcyclopentadienyl), with <b>L</b> = “click”-derived pyridyl-triazol, bis-triazole, or bis-abnormal carbene, were synthesized and spectroscopically characterized. Structural elucidation of the complexes shows a half-sandwich, piano-stool type of coordination around the metal centers and a delocalized situation within the triazolylidene rings. All the complexes were tested for their catalytic efficiency in the transfer hydrogenation of nitrobenzenes, and the results were compared with their 2,2′-bipyridine (bpy) Ru counterpart <b>1</b> and Ir counterpart <b>5</b>. Remarkably, the nature of the final catalytic product is strongly dependent on the chosen metal center, with aniline being preferentially formed with the Ru complexes and azobenzenes with the Ir complexes. Judicious selection of catalyst and reaction conditions also facilitates the isolation of azoxybenzene. To the best of our knowledge, this is a rare example of a homogeneous catalytic synthesis of azobenzene from nitrobenzene. The influence of ligand substitution, metal substitution, and temperature variation on catalytic activity and selectivity has been investigated, whereby a systematic variation of the ligands from bpy, to pyridyl-triazole, to bis-triazole, to bis-abnormal carbene has been carried out. We also present a mechanistic investigation for this transformation with the aim of understanding reaction behavior

Mono- and Digold(I) Complexes with Mesoionic Carbenes: Structural Characterization and Use in Catalytic Silver-Free Oxazoline Formation

Triazolylidenes are a prominent class of mesoionic carbenes that have found use as supporting ligands in homogeneous catalysis in recent years. We present here the syntheses of three new mononuclear gold­(I) chlorido and two new dinuclear gold­(I) chlorido complexes. The ligands in the aforementioned complexes are derived from either the corresponding monotriazolium or the bitriazolium salts. All complexes have been characterized by ¹H and ¹³C­{¹H} NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction studies. Structural characterization delivers a delocalized bonding situation within the triazolylidene ligands and a linear coordination at the gold­(I) centers. The gold­(I) centers in all cases are bound to one triazolylidene-<i>C</i> donor and a chlorido ligand. Additionally, for the digold­(I) complexes large Au–Au distances were observed, ruling out the existence of aurophilic interactions in these digold complexes in the solid state. All of the gold­(I) complexes were tested as (pre)­catalysts for the cyclization reaction of propargylic amides to form oxazolines. We show here that the steric bulk of the substituents on the triazolylidene ligands plays a decisive role in the catalytic efficiency of the gold­(I) complexes. Copper­(II) triflate is shown as a viable alternative to silver­(I) salts as an additive for the oxazoline formation. Mechanistic studies show the detection of a gold­(I) triazolylidene vinyl complex as an intermediate in the catalytic synthesis of oxazoline with these complexes. These results thus establish copper­(II) triflate as an alternative to silver­(I) salts as an additive in gold­(I) triazolylidene catalysis. Furthermore, it also shows that steric tuning of triazolylidene ligands can indeed be utilized for increasing the catalytic efficiency of the corresponding complexes

Gauging Donor/Acceptor Properties and Redox Stability of Chelating Click-Derived Triazoles and Triazolylidenes: A Case Study with Rhenium(I) Complexes

Bidentate ligands containing at least one triazole or triazolylidene (mesoionic carbene, MIC) unit are extremely popular in contemporary chemistry. One reason for their popularity is the similarities as well as differences in the donor/acceptor properties that these ligands display in comparison to their pyridine or other N-heterocyclic carbene counterparts. We present here seven rhenium­(I) carbonyl complexes where the bidentate ligands contain combinations of pyridine/triazole/triazolylidene. These are the first examples of rhenium­(I) complexes with bidentate 1,2,3-triazol-5-ylidene-containing ligands. All complexes were structurally characterized through ¹H and ¹³C NMR spectroscopy as well as through single-crystal X-ray diffraction. A combination of structural data, redox potentials from cyclic voltammetry, and IR data related to the CO coligands are used to gauge the donor/acceptor properties of these chelating ligands. Additionally, a combination of UV–vis–near-IR/IR/electron paramagnetic resonance spectroelectrochemistry and density functional theory calculations are used to address questions related to the electronic structures of the complexes in various redox states, their redox stability, and the understanding of chemical reactivity following electron transfer in these systems. The results show that donor/acceptor properties in these bidentate ligands are sometimes, but not always, additive with respect to the individual components. Additionally, these results point to the fact that MIC-containing ligands confer remarkable redox stability to their <i>fac</i>-Re­(CO)₃-containing metal complexes. These findings will probably be useful for fields such as homogeneous- and electro-catalysis, photochemistry, and electrochemistry, where <i>fac</i>-Re­(CO)₃ complexes of triazoles/triazolylidenes are likely to find use

Influence of Mesoionic Carbenes on Electro- and Photoactive Ru and Os Complexes: A Combined (Spectro-)Electrochemical, Photochemical, and Computational Study

International audienc

The Power of Ferrocene, Mesoionic Carbenes, and Gold: Redox-Switchable Catalysis

Catalysis with gold­(I) complexes is a useful route for synthesizing a variety of important heterocycles. Often, silver­(I) additives are necessary to increase the Lewis acidity at the gold­(I) center and to make them catalytically active. We present here a concept in redox-switchable gold­(I) catalysis that is based on the use of redox-active mesoionic carbenes, and of electron transfer steps for increasing the Lewis acidity at the gold­(I) center. A gold­(I) complex with a mesoionic carbene containing a ferrocenyl backbone is presented. Investigations on the corresponding iridium­(I)–CO complex show that the donor properties of such carbenes can be tuned via electron transfer steps to make these seemingly electron rich mesoionic carbenes relatively electron poor. A combined crystallographic, electrochemical, UV–vis–near-IR/IR spectroelectrochemical investigation together with DFT calculations is used to decipher the geometric and the electronic structures of these complexes in their various redox states. The gold­(I) mesoionic carbene complexes can be used as redox-switchable catalysts, and we have used this concept for the synthesis of important heterocycles: oxazoline, furan and phenol. Our approach shows that a simple electron transfer step, without the need of any silver additives, can be used as a trigger in gold catalysis. This report is thus the first instance where redox-switchable (as opposed to only redox-induced) catalysis has been observed with gold­(I) complexes

Fluorinated click-derived tripodal ligands drive spin crossover in both iron(ii) and cobalt(ii) complexes

Control of the spin state of metal complexes is important because it leads to a precise control over the physical properties and the chemical reactivity of the metal complexes. Currently, controlling the spin state in metal complexes is challenging because a precise control of the properties of the secondary coordination sphere is often difficult. It has been shown that non-covalent interactions in the secondary coordination sphere of transition metal complexes can enable spin state control. Here we exploit this strategy for fluorinated triazole ligands and present mononuclear CoII and FeII complexes with “click”-derived tripodal ligands that contain mono-fluorinated benzyl substituents on the backbone. Structural characterization of 1 and 2 at 100 K revealed Co-N bond lengths that are typical of high spin (HS) CoII complexes. In contrast, the Fe-N bond lengths for 3 are characteristic of a low spin (LS) FeII state. All complexes show an intramolecular face-to-face non-covalent interaction between two arms of the ligand. The influence of the substituents and of their geometric structure on the spin state of the metal center was investigated through SQUID magnetometry, which revealed spin crossover occurring in compounds 1 and 3. EPR spectroscopy sheds further light on the electronic structures of 1 and 2 in their low- and high-spin states. Quantum-chemical calculations of the fluorobenzene molecule were performed to obtain insight into the influence of fluorine-specific interactions. Interestingly, this work shows that the same fluorinated tripodal ligands induce SCO behavior in both FeII and CoII complexes.Fil: Nößler, Maite. Freie Universität Berlin; AlemaniaFil: Hunger, David. Universität Stuttgart; AlemaniaFil: Neuman, Nicolás Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Reimann, Marc. Technishe Universitat Berlin; AlemaniaFil: Reichert, Felix. Universität Stuttgart; AlemaniaFil: Winkler, Mario. Universität Stuttgart; AlemaniaFil: Klein, Johannes. Freie Universität Berlin; AlemaniaFil: Bens, Tobias. Universität Stuttgart; AlemaniaFil: Suntrup, Lisa. Freie Universität Berlin; AlemaniaFil: Demeshko, Serhiy. Universität Göttingen; AlemaniaFil: Stubbe, Jessica. Freie Universität Berlin; AlemaniaFil: Kaupp, Martin. Technishe Universitat Berlin; AlemaniaFil: van Slageren, Joris. Universität Stuttgart; AlemaniaFil: Sarkar, Biprajit. Universität Stuttgart; Alemania. Freie Universität Berlin; Alemani