The impact of repeated temperature cycling on cryopreserved human iPSC viability stems from cytochrome redox state changes.

Human induced pluripotent stem cells (hiPSCs) are an attractive cell source for regenerative medicine. For its widespread use as a starting material, a robust storage and distribution system in the frozen state is necessary. For this system, managing transient warming during storage and transport is essential, but how transient warming affects cells and the mechanisms involved are not yet fully understood. This study examined the influence of temperature cyclings (from -80°C to -150°C) on cryopreserved hiPSCs using a custom-made cryo Raman microscope, flow cytometry, and performance indices to assess viability. Raman spectroscopy indicated the disappearance of mitochondrial cytochrome signals after thawing. A reduction in the mitochondrial membrane potential was detected using flow cytometry. The performance indices indicated a decrease in attachment efficiency with an increase in the number of temperature cycles. This decrease was observed in the temperature cycle range above the glass transition temperature of the cryoprotectant. Raman observations captured an increase in the signal intensity of intracellular dimethyl sulfoxide (DMSO) during temperature cycles. Based on these results, we proposed a schematic illustration for cellular responses to temperature fluctuations, suggesting that temperature fluctuations above the glass-transition temperature trigger the movement of DMSO, leading to cytochrome c oxidation, mitochondrial damage, and caspase-mediated cell death. This enhances our understanding of the key events during cryopreservation and informs the development of quality control strategies for hiPSC storage and transport.

Bridging Titanium Nitrido Complexes Containing A Linear Ti-N-Ti Core with A Two-Coordinate Nitrido Ligand.

A series of titanium m2-nitrido complexes supported by the triamidoamine ligand Xy-N3N (Xy-N3N = {(3,5-Me2C6H3)NCH2CH2}3N3-) is reported. The titanium azido complex [(Xy-N3N)TiN3] (1-N3), prepared by salt metathesis of the chloride complex [(Xy-N3N)TiCl] (1-Cl) with NaN3, reacted with lithium metal or with alkali metal naphthalenides (alkali metal M = Na, K, and Rb) in THF to give the corresponding dinuclear m2-nitrido complexes M[(Xy-N3N)Ti=N-Ti(Xy-N3N)] (2-M; M = Li, Na, K, Rb). Single crystal X-ray diffraction studies of 2-Li, 2-Na, and 2-K revealed alkali metal dependent structures in the solid state. While 2-Li and 2-K contain a m2-nitrido ligand with a linear Ti-N-Ti core, 2-Na includes a m3-nitrido ligand as part of a T-shape Ti2NaN fragment with the sodium cation weekly coordinated to the nitrido nitrogen atom. When the synthesis of the nitrido complexes was carried out in the presence of excess alkali metals, selective decomposition of the nitrido complexes was observed affording some intractable titanium species along with the trialkali metal salts [M3(Xy-N3N)] (3-M) (M = Li, Na, K, and Rb). These salts were also prepared by deprotonation of (Xy-N3N)H3 with the corresponding alkali metal hexamethyldisilazide and characterized by multinuclear NMR spectroscopy as well as single crystal X-ray diffraction.

Grubbs-Hoveyda catalysts conjugated to a ß-barrel protein: Effect of halide substitution on aqueous olefin metathesis activity.

The effect of halide substitution in Grubbs-Hoveyda II catalysts (GHII catalysts) embedded in the engineered ß-barrel protein nitrobindin (NB4exp) on metathesis activity in aqueous media was studied. Maleimide tagged dibromido and diiodido derivates of the GHII catalyst were synthesized and covalently conjugated to NB4exp. The biohybrid catalysts were characterized spectroscopically confirming the structural integrity. When the two chloride substituents at ruthenium center were exchanged against bromide and iodide, the diiodo derivative was found to show significantly higher catalytic activity in ring-closing metathesis of α,ω-diolefins, whereas the dibromido derivative was less efficient when compared with the parent dichlorido catalyst. Using the diiodido catalyst, high turnover numbers of up to 75 were observed for ring-closing metathesis (RCM) yielding unsaturated six- and seven-membered N-heterocycles.

Hydrogenolysis of Cationic Half-Sandwich Zinc Complexes Containing a Chelating Amine: Facile Cleavage of Zinc-Carbon Bond by Dihydrogen to Give Zinc Hydride Cations.

Cationic half-sandwich zinc complexes containing chelating amines [Cp*Zn(Ln)][BAr4 F] (2 a, Cp*=η3-C5Me5, Ln=N,N,N',N'-tetramethylethylenediamine, TMEDA; 2 b, Ln=N,N,N',N'-tetraethylethylenediamine, TEEDA; 2 c, Cp*=η1-C5Me5, Ln=N,N,N',N'',N''-pentamethyldiethylenetriamine, PMDTA; Ar4 F=(3,5-(CF3)2C6H3)4) reacted with dihydrogen (ca. 2 bar) in THF at 80 °C to give molecular zinc hydride cations [(Ln)ZnH(thf)m][BAr4 F] (3 a,b, m=1; 3 c, m=0) previously reported along with Cp*H. Pseudo first-order kinetics with respect to the concentration of 2 b suggests heterolytic cleavage of dihydrogen by the Zn-Cp* bond, reminiscent of σ-bond metathesis. Hydrogenolysis of the zinc cation 2 b in the presence of benzophenone gave the zinc alkoxide [(TEEDA)Zn(OCHPh2)(thf)][BAr4 F] (5 b). Cation 2 b was shown to catalytically hydrogenate N-benzylideneaniline. The PMDTA complex 2 c underwent C-H bond activation in acetonitrile to give a dinuclear µ-κC,κN-cyanomethyl zinc complex [(PMDTA)Zn(CH2CN)]2[BAr4 F]2 (6 c).

Dihydrogen Cleavage by a Zinc-Zinc Bond of a Heteroleptic Dizinc(I) Cation.

Oxidative addition of dihydrogen across a metal-metal bond to form reactive metal hydrides in homogeneous catalysis is known for transition metals but not for zinc(I)-zinc(I) bond as found in Carmona's eponymous dizinconene [Zn2Cp*2] (Cp* = η5-C5Me5). Dihydrogen reacted with the heteroleptic zinc(I)-zinc(I) bonded cation [(L2)Zn-ZnCp*][BAr4F] (L2 = TMEDA, N,N,N',N'-tetramethylethylenediamine, TEEDA, N,N,N',N'-tetraethylethylenediamine; ArF = 3,5-(CF3)2C6H3) under 2 bar at 80 °C to give the zinc(II) hydride cation [(L2)ZnH(thf)][BAr4F] along with zinc metal and Cp*H derived from the intermediate [Cp*ZnH]. DFT calculations show that the cleavage of dihydrogen occurs through a highly unsymmetrical transition state. Mechanistic studies agree with a heterolytic cleavage of dihydrogen as a result of the cationic charge and unsymmetrical ligand coordination. To explore the existence of zinc(I) hydride, thermally unstable hydridotriphenylborate complexes of zinc(I) [(L2)Zn(HBPh3)-ZnCp*] (L2 = TMEDA, TEEDA; TMPDA, N,N,N',N'-tetramethyl-1,3-propylenediamine) have been prepared by salt metathesis and were shown to undergo fast exchange with both BPh3 and [HBPh3]-.

Engineered Anchor Peptide LCI with a Cobalt Cofactor Enhances Oxidation Efficiency of Polystyrene Microparticles.

A typical component of polymer waste is polystyrene (PS) used in numerous applications, but degraded only slowly in the environment due to its hydrophobic properties. To increase the reactivity of polystyrene, polar groups need to be introduced. Here, biohybrid catalysts based on the engineered anchor peptide LCI_F16C are presented, which are capable of attaching to polystyrene microparticles and hydroxylating benzylic C-H bonds in polystyrene microparticles using commercially available oxone as oxidant. LCI peptides achieve a dense surface coverage of PS through monolayer formation within minutes in aqueous solutions at ambient temperature. The catalytically active cobalt cofactor Co-L1 or Co-L2 with a modified NNNN macrocyclic TACD ligand (TACD=1,4,7,10-tetraazacyclododecane) is covalently bound to the anchor peptide LCI through a maleimide linker. Compared to the free cofactors, a 12- to 15-fold improvement in catalytic activity using biohybrid catalysts based on LCI_F16C was observed.

Benzylic C(sp3 )-H Bond Oxidation with Ketone Selectivity by a Cobalt(IV)-Oxo Embedded in a ß-Barrel Protein.

Artificial metalloenzymes have emerged as biohybrid catalysts that allow to combine the reactivity of a metal catalyst with the flexibility of protein scaffolds. This work reports the artificial metalloenzymes based on the ß-barrel protein nitrobindin NB4, in which a cofactor [CoII X(Me3 TACD-Mal)]+ X- (X=Cl, Br; Me3 TACD=N,N' ,N''-trimethyl-1,4,7,10-tetraazacyclododecane, Mal=CH2 CH2 CH2 NC4 H2 O2 ) was covalently anchored via a Michael addition reaction. These biohybrid catalysts showed higher efficiency than the free cobalt complexes for the oxidation of benzylic C(sp3 )-H bonds in aqueous media. Using commercially available oxone (2KHSO5 ⋅ KHSO4 ⋅ K2 SO4 ) as oxidant, a total turnover number of up to 220 and 97 % ketone selectivity were achieved for tetralin. As catalytically active intermediate, a mononuclear terminal cobalt(IV)-oxo species [Co(IV)=O]2+ was generated by reacting the cobalt(II) cofactor with oxone in aqueous solution and characterized by ESI-TOF MS.

Cationic tetranuclear macrocyclic CaCo3 complexes as highly active catalysts for alternating copolymerization of propylene oxide and carbon dioxide.

We found that a cationic hetero tetranuclear complex including a calcium and three cobalts exhibited high catalytic activity toward alternating copolymerization of propylene oxide (PO) and carbon dioxide (CO2). The tertiary anilinium salt [PhNMe2H][B(C6F5)4] was the best additive to generate the cationic species while maintaining polymer selectivity and carbonate linkage, even under 1.0 MPa CO2. Density functional theory calculations clarified that the reaction pathway mediated by the cationic complex is more favorable than that mediated by the neutral complex by 1.0 kcal mol-1. We further found that the flexible ligand exchange between Ca and Co ions is important for the alternating copolymerization to proceed smoothly.

Heterobimetallic Hydrides with a Germanium(II)-Zinc Bond.

In the presence of TMEDA (TMEDA=N,N,N',N'-tetramethylethylenediamine), zinc dihydride reacted with germanium(II) compounds (BDI-H)Ge (1) and [(BDI)Ge][B(3,5-(CF3 )2 C6 H3 )4 ] (3) (BDI-H = HC{(C=CH2 )(CMe)(NAr)2 }, BDI = [HC(CMeNAr)2 ]; Ar = 2,6-i Pr2 C6 H3 ) by formal insertion of the germanium(II) center into the Zn-H bond of polymeric [ZnH2 ]n to give neutral and cationic zincagermane with a H-Ge-Zn-H core [(BDI-H)Ge(H)-(H)Zn(tmeda)] (2) and [(BDI)Ge(H)-(H)Zn(tmeda)][B(3,5-(CF3 )2 C6 H3 )4 ] (4), respectively. Compound 2 eliminated [ZnH2 ] giving diamido germylene 1 at 60 °C. Compound 2 and deuterated analogue 2-d2 exchanged with [ZnH2 ]n and [ZnD2 ]n in the presence of TMEDA to give a mixture of 2 and 2-d2 . Compounds 2 and 4 reacted with carbon dioxide (1 bar) at room temperature to form zincagermane diformate [(BDI-H)Ge(OCHO)-(OCHO)Zn(tmeda)] (5) and formate bridged digermylene [({BDI}Ge)2 (µ-OCHO)]+ [B(C6 H3 (CF3 )2 )4 ] (6) along with zinc formate [(tmeda)Zn(µ-OCHO)3 Zn(tmeda)][B(C6 H3 (CF3 )2 )4 ] (7), respectively. The hydridic nature of the Ge-H and Zn-H bonds in 2 and 4 was probed by reactions with Brönsted and Lewis acids.

FhuA: From Iron-Transporting Transmembrane Protein to Versatile Scaffolds through Protein Engineering.

Protein engineering has emerged as a powerful methodology to tailor the properties of proteins. It empowers the design of biohybrid catalysts and materials, thereby enabling the convergence of materials science, chemistry, and medicine. The choice of a protein scaffold is an important factor for performance and potential applications. In the past two decades, we utilized the ferric hydroxamate uptake protein FhuA. FhuA is, from our point of view, a versatile scaffold due to its comparably large cavity and robustness toward temperature as well as organic cosolvents. FhuA is a natural iron transporter located in the outer membrane of Escherichia coli (E. coli). Wild-type FhuA consists of 714 amino acids and has a ß-barrel structure composed of 22 antiparallel ß-sheets, closed by an internal globular "cork" domain (amino acids 1-160). FhuA is robust in a broad pH range and toward organic cosolvents; therefore, we envisioned FhuA to be a suitable platform for various applications in (i) biocatalysis, (ii) materials science, and (iii) the construction of artificial metalloenzymes.(i) Applications in biocatalysis were achieved by removing the globular cork domain (FhuA_Δ1-160), thereby creating a large pore for the passive transport of otherwise difficult-to-import molecules through diffusion. Introducing this FhuA variant into the outer membrane of E. coli facilitates the uptake of substrates for downstream biocatalytic conversion. Furthermore, removing the globular "cork" domain without structural collapse of the ß-barrel protein allowed the use of FhuA as a membrane filter, exhibiting a preference for d-arginine over l-arginine.(ii) FhuA is a transmembrane protein, which makes it attractive to be used for applications in non-natural polymeric membranes. Inserting FhuA into polymer vesicles yielded so-called synthosomes (i.e., catalytic synthetic vesicles in which the transmembrane protein acted as a switchable gate or filter). Our work in this direction enables polymersomes to be used in biocatalysis, DNA recovery, and the controlled (triggered) release of molecules. Furthermore, FhuA can be used as a building block to create protein-polymer conjugates to generate membranes.(iii) Artificial metalloenzymes (ArMs) are formed by incorporating a non-native metal ion or metal complex into a protein. This combines the best of two worlds: the vast reaction and substrate scope of chemocatalysis and the selectivity and evolvability of enzymes. With its large inner diameter, FhuA can harbor (bulky) metal catalysts. Among others, we covalently attached a Grubbs-Hoveyda-type catalyst for olefin metathesis to FhuA. This artificial metathease was then used in various chemical transformations, ranging from polymerizations (ring-opening metathesis polymerization) to enzymatic cascades involving cross-metathesis. Ultimately, we generated a catalytically active membrane by copolymerizing FhuA and pyrrole. The resulting biohybrid material was then equipped with the Grubbs-Hoveyda-type catalyst and used in ring-closing metathesis.The number of reports on FhuA and its various applications indicates that it is a versatile building block to generate hybrid catalysts and materials. We hope that our research will inspire future research efforts at the interface of biotechnology, catalysis, and material science in order to create biohybrid systems that offer smart solutions for current challenges in catalysis, material science, and medicine.

Hydroboration and Deoxygenation of CO2 Mediated by a Gallium(I) Cation.

Hydroboration of CO2 to formoxy borane occurs under ambient conditions in acetonitrile using pinacolborane HBpin in the presence of gallium(I) cation [(Me4TACD)Ga][BAr4] (1; Me4TACD = N,N',N″,N'''-tetramethyl-1,4,7,10-tetraazacyclododecane; Ar = C6H3-3,5-Me2). Slow turnover was accompanied by side reactions including ligand scrambling of HBpin to give BH3(CH3CN) and crystalline B2pin3. When 1 was reacted with CO2 alone, the formation of the gallium(III) carbonato complex [(Me4TACD)Ga(κ2-O2CO)][BAr4] (3) along with CO was observed. This complex was assumed to form via the unstable oxido cation [(Me4TACD)Ga=O]+ (4). Reaction of 1 with N2O in the presence of BPh3 confirmed the formation of the oxido cation, which was spectroscopically characterized as a triphenylborane adduct [(Me4TACD)Ga=O(BPh3)][BAr4] (4·BPh3). CO was also detected when CO2 was reacted with 1 in the presence of HBpin, suggesting that compound 3 may also be formed in initial stages of catalysis. Compound 3 reacts with HBpin to give formoxy borane, borane redistribution products, and an unidentified Me4TACD-containing species 5, which was also observed in "catalytic" runs starting from 1, HBpin, and CO2. Hydroboration of CO2 using HBpin with slow turnover and competitive ligand scrambling was also observed in the presence of gallium(III) hydride dication [(Me4TACD)GaH][BAr4]2 (2), which is unreactive toward CO2 in the absence of HBpin.

Formate complexes of tri- and tetravalent titanium supported by a tris(phenolato)amine ligand.

Titanium(III) and titanium(IV) formate complexes supported by the sterically encumbering tris(phenolato)amine ligand (H3(O3N) = tris(4,6-di-tert-butyl-2-hydroxybenzyl)amine) are described. Salt metathesis of the chlorido precursor [(O3N)TiCl] (1-Cl) with sodium formate in a 2 : 1 ratio in THF gave a dimer of sodium dititanium triformate units with 12-membered ring [Na{(O3N)Ti}2(µ-OCHO-ηO:ηO')3]2 (3-Na) when crystallized from acetonitrile. Complex 3-Na was also prepared by reacting the previously reported terminal formate complex [(O3N)Ti(OCHO)] (2) with excess sodium formate. Salt metathesis of 1-Cl with potassium formate gave a tetratitanium cluster of the composition [K3{(O3N)Ti}4(OCHO)7] (3-K) which can be also obtained by treating 2 with potassium formate. In 3-K both Ti and K centers are six-coordinate. The titanium(III) complexes [(O3N)Ti(L)] (4-L, L = THF, THP, Et2O) and solvent free dimeric [(O3N)Ti]2 (5) were synthesized by reduction of 1-Cl with sodium sand or magnesium in THF, THP, Et2O, and n-pentane, respectively. The tert-butyl formate adduct of titanium(III)-[(O3N)Ti(tBuOCHO)] (6) was isolated by reacting 4-L or 5 with tert-butyl formate. Complex 6 is thermolabile and slowly decomposed in solution to produce a formate-bridged mixed-valence titanium(III)/titanium(IV) complex [{(O3N)Ti}2(µ-OCHO-ηO:ηO')] (7) which further decomposed to a mixture containing 2, [(O3N)Ti(OH)] and [(O3N)Ti-O-Ti(O3N)]. All new complexes were isolated in moderate to good yields and fully characterized by elemental analysis, 1H and 13C NMR spectroscopy, and single crystal X-ray diffraction analysis. For the titanium(III) complexes solution magnetic moments were measured by the Evans method and EPR spectra recorded as toluene glass at 77 K.

Solvent-Dependent Oxidative Addition and Reductive Elimination of H2 Across a Gallium-Zinc Bond.

H2 adds reversibly across the metal-metal bond of [(BDI)Ga(H)-Zn(tmeda)(thf)][BAr4 F ] (BDI=[HC{C(CH3 )N(2,6-iPr2 -C6 H3 )}2 ]- , TMEDA=N,N,N',N'-tetramethylethylenediamine, BAr4 F- =[B(C6 H3 -3,5-(CF3 )2 )4 ]- ). Due to the stabilising effect of solvent coordination, hydrogenation products [(BDI)GaH2 ] and [(tmeda)ZnH(thf)][BAr4 F ] are favoured in THF solution, but THF-free mixtures of [(BDI)GaH2 ] and [(tmeda)ZnH(OEt2 )][BAr4 F ] are predisposed towards entropically driven dehydrogenation to [(BDI)Ga(H)-Zn(tmeda)][BAr4 F ] in fluorobenzene solution.

Reversible Oxidative Addition of Zinc Hydride at a Gallium(I)-Centre: Labile Mono- and Bis(hydridogallyl)zinc Complexes.

In the presence of TMEDA (N,N,N',N'-tetramethylethylenediamine), partially deaggregated zinc dihydride as hydrocarbon suspensions react with the gallium(I) compound [(BDI)Ga] (I, BDI={HC(C(CH3 )N(2,6-iPr2 -C6 H3 ))2 }- ) by formal oxidative addition of a Zn-H bond to the gallium(I) centre. Dissociation of the labile TMEDA ligand in the resulting complex [(BDI)Ga(H)-(H)Zn(tmeda)] (1) facilitates insertion of a second equiv. of I into the remaining Zn-H to form a thermally sensitive trinuclear species [{(BDI)Ga(H)}2 Zn] (2). Compound 1 exchanges with polymeric zinc dideuteride [ZnD2 ]n in the presence of TMEDA, and with compounds I and 2 via sequential and reversible ligand dissociation and gallium(I) insertion. Spectroscopic and computational studies demonstrate the reversibility of oxidative addition of each Zn-H bond to the gallium(I) centres.

Strontium Hydride Cations Supported by a Large NNNNN Type Macrocycle: Synthesis, Structure, and Hydrofunctionalization Catalysis.

The use of the 15-membered NNNNN macrocyclic ligand Me5PACP (Me5PACP = 1,4,7,10,13-pentamethyl-1,4,7,10,13-pentaazacyclopentadecane) allowed the isolation of two cationic strontium hydride complexes by hydrogenolysis of benzyl precursors. Treatment of sparingly soluble [(Me5PACP)Sr(CH2Ph)2] with dihydrogen gave free Me5PACP, toluene, and oligomeric strontium hydride [SrH2]n, while hydrogenolysis in the presence of 1 equiv of the benzyl cation [(Me5PACP)Sr(CH2Ph)][B(C6H3-3,5-Me2)4] enabled isolation of the thermally unstable trihydride cation [(Me5PACP)2Sr2(µ-H)3][B(C6H3-3,5-Me2)4]. When the benzyl cation [(Me5PACP)Sr(CH2Ph)][BAr4]2 (Ar = C6H3-3,5-Me2 or C6H4-4-nBu) was reacted with dihydrogen or n-octylsilane, dihydride complexes [(Me5PACP)2Sr2(µ-H)2][BAr4]2 containing a dinuclear core bridged by two hydride ligands were obtained. The soluble dihydride complex [(Me5PACP)2Sr2(µ-H)2][B(C6H4-4-nBu)4]2 was tested in olefin hydrogenation and hydrosilylation catalysis. Kinetic analyses for [(Me5PACP)2Sr2(µ-H)2]2+ showed lower catalytic activity as compared to that of the isostructural calcium homologue [(Me5PACP)2Ca2(µ-H)2]2+. This is explained by a shift in the monomer-dimer equilibrium which precedes the catalytic cycle.

Strategies Employed by Forensic Community Mental Health Nurses to Resolve Difficulties in Supporting Offenders With Mental Disorders Under the Medical Treatment and Supervision Act in Japan.

OBJECTIVE: This study aimed to identify the strategies used by forensic community mental health nurses to resolve difficulties in supporting offenders with mental disorders under the Medical Treatment and Supervision Act in Japan. METHOD: Interviews were conducted with 13 nurses, and the data were analyzed using content analysis. RESULTS: The study identified the strategies for difficulties in (a) assessing and managing risk potential of forensic service patients, (b) addressing offending behavior, (c) managing the transition of patients, (d) supporting patients to understand the impact of justice processes and applying knowledge of legislation to nursing, and (e) promoting the role of forensic community mental health nurses within the multidisciplinary team. CONCLUSIONS: The findings can benefit and support forensic community mental health nurses' practices. The Japanese forensic community mental health nurses experiencing difficulties and providing home visits to patients can utilize the identified strategies.

Formation and Reactivity of a Hexahydridosilicate [SiH6 ]2- Coordinated by a Macrocycle-Supported Strontium Cation.

The cationic benzyl complex [(Me4 TACD)Sr(CH2 Ph)][A] (Me4 TACD=1,4,7,10-tetramethyltetraazacyclododecane; A=B(C6 H3 -3,5-Me2 )4 ) reacted with two equivalents of phenylsilane to give the bridging hexahydridosilicate complex [(Me4 TACD)2 Sr2 (thf)4 (µ-κ3 : κ3 -SiH6 )][A]2 (3 a). Rapid phenyl exchange between phenylsilane molecules is assumed to generate monosilane SiH4 that is trapped by two strontium hydride cations [(Me4 TACD)SrH(thf)x ]+ . Complex 3 a decomposed in THF at room temperature to give the terminal silanide complex [(Me4 TACD)Sr(SiH3 )(thf)2 ][A], with release of H2 . Upon reaction with a weak Brønsted acid, CO2 , and 1,3,5,7-cyclooctatetraene SiH4 was released. The reaction of a 1 : 2 mixture of cationic benzyl and neutral dibenzyl complex with phenylsilane gave the trinuclear silanide complex [(Me4 TACD)3 Sr3 (µ2 -H)3 (µ3 -SiH3 )2 ][A], while n OctSiH3 led to the trinuclear (n-octyl)pentahydridosilicate complex [(Me4 TACD)3 Sr3 (µ2 -H)3 (µ3 -SiH5 n Oct)][A].

A Brønsted Acidic Gallium Hydride: Facile Interconversion of NNNN-Macrocycle Supported [GaI ]+ and [GaIII H]2.

Protonolysis of [Cp*M] (M=Ga, In, Tl) with [(Me4 TACD)H][BAr4 Me ] (Me4 TACD=N,N',N'',N'''-tetramethyl-1,4,7,10-tetraazacyclododecane; [BAr4 Me ]- =[B{C6 H3 -3,5-(CH3 )2 }4 ]- ) provided monovalent salts [(Me4 TACD)M][BAr4 Me ], whereas [Cp*Al]4 yielded trivalent [(Me4 TACD)AlH][BAr4 Me ]2 . Protonation of [(Me4 TACD)Ga][BAr4 Me ] with [Et3 NH][BAr4 Me ] gave an unusually acidic (pKa (CH3 CN)=24.5) gallium(III) hydride dication [(Me4 TACD)GaH][BAr4 Me ]2 . Deprotonation with IMe4 (1,3,4,5-tetramethyl-imidazol-ylidene) returned [(Me4 TACD)Ga][BAr4 Me ]. These reversible processes occur with formal two-electron oxidation and reduction of gallium. DFT calculations suggest that gallium(I) protonation is facilitated by strong coordination of the tetradentate ligand, which raises the HOMO energy. High nuclear charge of [(Me4 TACD)GaH]2+ facilitates hydride-to-metal charge transfer during deprotonation. Attempts to prepare a gallium(III) dihydride cation resulted in spontaneous dehydrogenation to [(Me4 TACD)Ga]+ .

Effects of Thoracic Epidural Anesthesia on Systemic and Local Inflammatory Responses in Patients Undergoing Lung Cancer Surgery: A Randomized Controlled Trial.

OBJECTIVE: Inflammatory responses play major roles in the development of acute lung injury following lung cancer surgery. The authors tested the hypothesis that thoracic epidural anesthesia (TEA) during surgery could attenuate both systemic and local inflammatory cytokine productions in patients undergoing lung cancer surgery. DESIGN: A prospective randomized controlled trial. SETTING: At Keio University Hospital, Tokyo, Japan. PARTICIPANTS: Patients scheduled for lung cancer surgery. INTERVENTIONS: Sixty patients were randomly allocated into two groups (n = 30 each group): the epidural group (group E), in which anesthesia was maintained with propofol, fentanyl, rocuronium, and epidural anesthesia with 0.25% levobupivacaine; or the remifentanil group (group R), in which a remifentanil infusion was used as a potent analgesia instead of epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: The lung epithelial lining fluid (ELF) and blood sampling were collected prior to one-lung ventilation (OLV) initiation (T1) and at 30 minutes after the end of OLV (T2). The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the ELF at T2 were increased significantly compared with those at T1 in both groups. The ELF concentration of IL-6 in group E was significantly lower than that in group R at T2 (median [interquartile range]: 39.7 [13.8-80.2] versus 76.1 [44.9-138.2], p = 0.008). Plasma IL-6 concentrations at T2, which increased in comparison to that at T1, were not significantly different between the two groups. The plasma concentrations of TNF-α did not change in both groups. CONCLUSIONS: This randomized clinical trial suggested that TEA could attenuate local inflammatory responses in the lungs during lung cancer surgery.

Aerobic oxygenation of α-methylene ketones under visible-light catalysed by a CeNi3 complex with a macrocyclic tris(salen)-ligand.

A hetero-tetranuclear CeNi3 complex with a macrocyclic ligand catalysed the aerobic oxygenation of a methylene group adjacent to a carbonyl group under visible-light radiation to produce the corresponding α-diketones. The visible-light induced homolysis of the Ce-O bond of a bis(enolate) intermediate is proposed prior to aerobic oxygenation.