Stronger Together! Mechanistic Investigation into Synergistic Effects during Homogeneous Carbon Dioxide Hydrogenation Using a Heterobimetallic Catalyst.

A series of group 6 heterobimetallic complexes [M0;IrIII] (M = Cr, Mo, W) were synthesized and fully characterized, and the catalytic behavior was studied. The heterobimetallic complex [Mo0;IrIII] (C1) was by far the most active and has shown a considerable synergistic effect, with both metals actively participating in homogeneous carbon dioxide hydrogenation, leading to formate salts. Based on theoretical calculations, the synergistic interaction is due to Pauli repulsion, lowering the transition state and thus enabling higher catalytic activity. The mechanism of both the hydrogenation itself and the synergistic interaction was studied by NMR spectroscopy, kinetic measurements, and theoretical calculations. The homogeneous nature of the reaction was proven using in situ high-pressure (HP) NMR experiments. The same experiments also showed that the octahedral Mo(CO)3P3 moiety of the complex is stable under the reaction conditions. The hydride complex is the resting state because the hydride transfer is the rate-determining step. This is supported by kinetic measurements, in situ HP NMR experiments, and theoretical calculations and is in contrast to the monometallic IrIII counterpart of C1.

Low-Temperature Isolation of a Labile Silylated Hydrazinium-yl Radical Cation, [(Me3 Si)2 N-N(H)SiMe3 ].

The oxidation of silylated hydrazine, (Me3 Si)2 N-N(H)SiMe3 , with silver salts led to the formation of a highly labile hydrazinium-yl radical cation, [(Me3 Si)2 N-N(H)SiMe3 ].+ , at very low temperatures (decomposition > -40 °C). EPR, NMR, DFT and Raman studies revealed the formation of a nitrogen-centered radical cation along the N-N unit of the hydrazine. In the presence of the weakly coordinating anion [Al{OCH(CF3 )2 }4 ]- , crystallization and structural characterization in the solid state were achieved. The hydrazinium-yl radical cation has a significantly shortened N-N bond and a nearly planar N2 Si3 framework, in contrast to the starting material. According to DFT calculations, the shortened N-N bond has a total bond order of 1.5 with a π-bond order of 0.5. The π bond can be regarded as a three-π-electron, two-center bond.

Selective Oxidation of Clopidogrel by Peroxymonosulfate (PMS) and Sodium Halide (NaX) System: An NMR Study.

A selective transformation of clopidogrel hydrogen sulfate (CLP) by reactive halogen species (HOX) generated from peroxymonosulfate (PMS) and sodium halide (NaX) is described. Other sustainable oxidants as well as different solvents have also been investigated. As result of this study, for each sodium salt the reaction conditions were optimized, and four different degradation products were formed. Three products were halogenated at C-2 on the thiophene ring and have concomitant functional transformation, such as N-oxide in the piperidine group. A halogenated endo-iminium product was also observed. With this condition, a fast preparation of known endo-iminium clopidogrel impurity (new counterion) was reported as well. The progress of the reaction was monitored using nuclear magnetic resonance spectroscopy as an analytical tool and all the products were characterized by 1D-, 2D-NMR and HRMS.

New Antimycotics in the Pipeline - For Ophthalmology Too? / Neue Antimykotika in der Pipeline ­ auch für die Augenheilkunde?

Seven new antimycotics are presented that are at different points of development or approval. These substances are mainly first-in-class drugs. They are primarily developed for systemic administration. However, with the support of a pharmacist, the intravenous formulation may be used as eyedrops. In this short review, the activities of the substances against various fungal infections are described. After unsuccessful conventional therapy of fungal eye infections, one of these new substances might be suitable to cure the mycosis.

Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide.

Hydrogen produced from renewable resources is a promising potential source of clean energy. With the help of low-temperature proton-exchange membrane fuel cells, molecular hydrogen can be converted efficiently to produce electricity. The implementation of sustainable hydrogen production and subsequent hydrogen conversion to energy is called "hydrogen economy". Unfortunately, its physical properties make the transport and handling of hydrogen gas difficult. To overcome this, methanol can be used as a material for the storage of hydrogen, because it is a liquid at room temperature and contains 12.6 per cent hydrogen. However, the state-of-the-art method for the production of hydrogen from methanol (methanol reforming) is conducted at high temperatures (over 200 degrees Celsius) and high pressures (25-50 bar), which limits its potential applications. Here we describe an efficient low-temperature aqueous-phase methanol dehydrogenation process, which is facilitated by ruthenium complexes. Hydrogen generation by this method proceeds at 65-95 degrees Celsius and ambient pressure with excellent catalyst turnover frequencies (4,700 per hour) and turnover numbers (exceeding 350,000). This would make the delivery of hydrogen on mobile devices--and hence the use of methanol as a practical hydrogen carrier--feasible.

Keratomycosis due to Tintelnotia destructans refractory to common therapy treated successfully with systemic and local terbinafine in combination with polyhexamethylene biguanide.

PURPOSE: To report on a wearer of rigid gas-permeable contact lenses with a keratomycosis due to Tintelnotia-a new genus of Phaeosphaeriaceae-treated with terbinafine and polyhexamethylene biguanide. METHODS: Chart review of a patient with fungal keratitis treated additionally with systemic and topical terbinafine 0.25% after symptoms increased under conventional antimycotic therapy with voriconazole. Antifungal susceptibility had been tested in vitro. RESULTS: After starting an additional treatment with systemic and topical terbinafine, the severe corneal infection was sufficiently resolved. The drug was well tolerated without any neurological, dermatological or gastroenterological problems. Terbinafine revealed a marked in vitro antifungal activity of 0.12 µg/ml. The fungus was identified as Tintelnotia destructans. CONCLUSIONS: Terbinafine might be considered as a therapeutic option in severe cases of fungal keratitis refractory to common antifungal therapy.

Stereoselective Synthesis of Highly Substituted Conjugated Dienes via Pd-Catalyzed Carbonylation of 1,3-Diynes.

The stereoselective synthesis of conjugated dienes was realized for the first time via Pd-catalyzed alkoxycarbonylation of easily available 1,3-diynes. Key to success is the utilization of the specific ligand 1,1'-ferrocenediyl-bis(tert-butyl(pyridin-2-yl)phosphine) (L1), which allows this novel transformation to proceed at room temperature. A range of 1,2,3,4-tetrasubstituted conjugated dienes are obtained in this straightforward access in high yields and selectivities. The synthetic utility of the protocol is showcased in the concise synthesis of several important intermediates for construction of natural products rac-cagayanin, rac-galbulin, rac-agastinol, and cannabisin G.

Visiting the Limits between a Highly Strained 1-Zirconacyclobuta-2,3-diene and Chemically Robust Dizirconacyclooctatetraene.

The reaction of the allene precursor Li2 (Me3 SiC3 SiMe3 ) with [Cp2 ZrCl2 ] (Cp=cyclopentadienyl) was examined. The selective formation of hitherto unknown linear, allene-bridged dizirconocene complexes [(Cp2 ZrCl)2 {-µ-(Me3 Si)C3 (SiMe3 )-}] and [(Cp2 Zr)2 {-µ-(Me3 Si)C3 (SiMe3 )-}2 ] was observed. Upon σ coordination of the allenediyl unit to {Cp2 Zr}, pyrophoric Li2 (Me3 SiC3 SiMe3 ) is tamed stepwise to yield a surprisingly robust 1,5-dizirconacyclooctatetra-2,3,6,7-ene with cumulated double bonds. This complex is unexpectedly inert against moisture, air, water and acetone. Surprisingly, it degrades under MS conditions to give the highly strained 1-zirconacyclobuta-2,3-diene. All compounds isolated have been fully characterised and the molecular structures are discussed. The stability and reactivity of these complexes are rationalised by DFT computations.

Selective Hydrogenation of α,ß-Unsaturated Aldehydes and Ketones by Air-Stable Ruthenium NNS Complexes.

The selective hydrogenation of the carbonyl functionality of α,ß-unsaturated aldehydes and ketones is catalysed by ruthenium dichloride complexes bearing a tridentate NNS ligand as well as triphenylphosphine. The tridentate ligand backbone is flexible, as evidenced by the equilibrium observed in solution between the cis- and trans-isomers of the dichloride precatalysts, as well as crystal structures of several of these complexes. The complexes are activated by base in the presence of hydrogen and readily hydrogenate carbonyl functionalities under mild conditions. Despite the activation by base, side reactions are negligible, even for aldehyde substrates, because of the low amount of base. Thus, the corresponding allylic alcohols can be isolated in very good yields on a 10-25 mmol scale. Turnover numbers up to 200 000 were achieved.

VEP-based acuity assessment in low vision.

PURPOSE: Objective assessment of visual acuity (VA) is possible with VEP methodology, but established with sufficient precision only for vision better than about 1.0 logMAR. We here explore whether this can be extended down to 2.0 logMAR, highly desirable for low-vision evaluations. METHODS: Based on the stepwise sweep algorithm (Bach et al. in Br J Ophthalmol 92:396-403, 2008) VEPs to monocular steady-state brief onset pattern stimulation (7.5-Hz checkerboards, 40% contrast, 40 ms on, 93 ms off) were recorded for eight different check sizes, from 0.5° to 9.0°, for two runs with three occipital electrodes in a Laplace-approximating montage. We examined 22 visually normal participants where acuity was reduced to ≈ 2.0 logMAR with frosted transparencies. With the established heuristic algorithm the "VEP acuity" was extracted and compared to psychophysical VA, both obtained at 57 cm distance. RESULTS: In 20 of the 22 participants with artificially reduced acuity the automatic analysis indicated a valid result (1.80 logMAR on average) in at least one of the two runs. 95% test-retest limits of agreement on average were ± 0.09 logMAR for psychophysical, and ± 0.21 logMAR for VEP-derived acuity. For 15 participants we obtained results in both runs and averaged them. In 12 of these 15 the low-acuity results stayed within the 95% confidence interval (± 0.3 logMAR) as established by Bach et al. (2008). CONCLUSIONS: The fully automated analysis yielded good agreement of psychophysical and electrophysiological VAs in 12 of 15 cases (80%) in the low-vision range down to 2.0 logMAR. This encourages us to further pursue this methodology and assess its value in patients.

Low-Temperature Hydrogenation of Carbon Dioxide to Methanol with a Homogeneous Cobalt Catalyst.

Herein we describe the first homogeneous non-noble metal catalyst for the hydrogenation of CO2 to methanol. The catalyst is formed in situ from [Co(acac)3 ], Triphos, and HNTf2 and enables the reaction to be performed at 100 °C without a decrease in activity. Kinetic studies suggest an inner-sphere mechanism, and in situ NMR and MS experiments reveal the formation of the active catalyst through slow removal of the acetylacetonate ligands.

Selective Catalytic Hydrogenations of Nitriles, Ketones, and Aldehydes by Well-Defined Manganese Pincer Complexes.

Hydrogenations constitute fundamental processes in organic chemistry and allow for atom-efficient and clean functional group transformations. In fact, the selective reduction of nitriles, ketones, and aldehydes with molecular hydrogen permits access to a green synthesis of valuable amines and alcohols. Despite more than a century of developments in homogeneous and heterogeneous catalysis, efforts toward the creation of new useful and broadly applicable catalyst systems are ongoing. Recently, Earth-abundant metals have attracted significant interest in this area. In the present study, we describe for the first time specific molecular-defined manganese complexes that allow for the hydrogenation of various polar functional groups. Under optimal conditions, we achieve good functional group tolerance, and industrially important substrates, e.g., for the flavor and fragrance industry, are selectively reduced.

Unravelling the Mechanism of Basic Aqueous Methanol Dehydrogenation Catalyzed by Ru-PNP Pincer Complexes.

Ruthenium PNP complex 1a (RuH(CO)Cl(HN(C2H4Pi-Pr2)2)) represents a state-of-the-art catalyst for low-temperature (<100 °C) aqueous methanol dehydrogenation to H2 and CO2. Herein, we describe an investigation that combines experiment, spectroscopy, and theory to provide a mechanistic rationale for this process. During catalysis, the presence of two anionic resting states was revealed, Ru-dihydride (3-) and Ru-monohydride (4-) that are deprotonated at nitrogen in the pincer ligand backbone. DFT calculations showed that O- and CH- coordination modes of methoxide to ruthenium compete, and form complexes 4- and 3-, respectively. Not only does the reaction rate increase with increasing KOH, but the ratio of 3-/4- increases, demonstrating that the "inner-sphere" C-H cleavage, via C-H coordination of methoxide to Ru, is promoted by base. Protonation of 3- liberates H2 gas and formaldehyde, the latter of which is rapidly consumed by KOH to give the corresponding gem-diolate and provides the overall driving force for the reaction. Full MeOH reforming is achieved through the corresponding steps that start from the gem-diolate and formate. Theoretical studies into the mechanism of the catalyst Me-1a (N-methylated 1a) revealed that C-H coordination to Ru sets-up C-H cleavage and hydride delivery; a process that is also promoted by base, as observed experimentally. However, in this case, Ru-dihydride Me-3 is much more stable to protonation and can even be observed under neutral conditions. The greater stability of Me-3 rationalizes the lower rates of Me-1a compared to 1a, and also explains why the reaction rate then drops with increasing KOH concentration.

NNP-Type Pincer Imidazolylphosphine Ruthenium Complexes: Efficient Base-Free Hydrogenation of Aromatic and Aliphatic Nitriles under Mild Conditions.

A series of seven novel N(Im)N(H)P-type pincer imidazolylphosphine ruthenium complexes has been synthesized and fully characterized. The use of hydrogenation of benzonitrile as a benchmark test identified [RuHCl(CO)(N(Im)N(H) P(tBu))] as the most active catalyst. With its stable Ru-BH4 analogue, in which chloride is replaced by BH4, a broad range of (hetero)aromatic and aliphatic nitriles, including industrially interesting adiponitrile, has been hydrogenated under mild and base-free conditions.

Multiple and Highly Selective Alkyne-Isonitrile C-C and C-N Couplings at Group†4 Metallocenes.

Reactions of the group 4 metallocene alkyne complexes [Cp'2 M(η(2) -Me3 SiC2 SiMe3 )] [Cp'2 =rac-(ebthi)=rac-1,2-ethylene-1,1'-bis(η(5) -tetrahydroindenyl): M=Ti, Zr, Hf; Cp'2 =Cp*2 (Cp*=η(5) -pentamethylcyclopentadienyl): M=Zr] with 2,6-dimethylphenyl isocyanide (2-xylyl isonitrile, XyNC) were investigated. Depending on the metal, the Cp' ligand, and/or the stoichiometry, as well as the reaction temperature and time, different products were obtained. The products included simple end-on coordination compounds of XyNC in addition to those of the coupling of Me3 SiC2 SiMe3 with two, three, or four isonitriles to form enimine complexes, aza-metallacycloallenes, and fused heterocyclic systems, respectively. One example of the latter tricyclic compounds was subject to demetalation by using HCl. Molecular structures of the heterometallacycles were determined by X-ray crystallography. The interconversion of the products was investigated by (1) H NMR spectroscopy.

In Situ FTIR and NMR Spectroscopic Investigations on Ruthenium-Based Catalysts for Alkene Hydroformylation.

Homogeneous ruthenium complexes modified by imidazole-substituted monophosphines as catalysts for various highly efficient hydroformylation reactions were characterized by in situ IR spectroscopy under reaction conditions and NMR spectroscopy. A proper protocol for the preformation reaction from [Ru3 (CO)12] is decisive to prevent the formation of inactive ligand-modified polynuclear complexes. During catalysis, ligand-modified mononuclear ruthenium(0) carbonyls were detected as resting states. Changes in the ligand structure have a crucial impact on the coordination behavior of the ligand and consequently on the catalytic performance. The substitution of CO by a nitrogen atom of the imidazolyl moiety in the ligand is not a general feature, but it takes place when structural prerequisites of the ligand are fulfilled.

Feasibility study: 7 T MRI in giant cell arteritis.

OBJECTIVES: To assess the detectability of vasculitic changes of the superficial cranial arteries with contrast-enhanced 7 T MRI in three patients with GCA and intraindividual comparison with 3 T MRI. METHODS: Three patients (two female, one male) with suspected GCA underwent contrast-enhanced T1-weighted high-resolution MRI at 3 T and 7 T magnetic field strength. The clinical diagnosis, based on criteria of the American College of Rheumatology, was confirmed by biopsy of the superficial temporal artery after MRI. MR images were visually assessed for detection of vasculitic mural contrast enhancement and vessel wall thickening of the superficial cranial arteries. RESULTS: Both 3 T and 7 T MRI allows for visualisation of mural inflammatory changes and assessment of the vasculitic involvement pattern. Image quality of 7 T MRI was rated superior to image quality of 3 T MRI scans. CONCLUSIONS: 7 T MR imaging of vasculitic changes in patients with GCA is possible, and suggests superior image quality. Larger patient studies are necessary to quantify the diagnostic advantages of 7 T MRI.

Impact of chiasma opticum malformations on the organization of the human ventral visual cortex.

Congenital malformations of the optic chiasm, such as enhanced and reduced crossing of the optic nerve fibers, are evident in albinism and achiasma, respectively. In early visual cortex the resulting additional visual input from the ipsilateral visual hemifield is superimposed onto the normal retinotopic representation of the contralateral visual field, which is likely due to conservative geniculo-striate projections. Counterintuitively, this organization in early visual cortex does not have profound consequences on visual function. Here we ask, whether higher stages of visual processing provide a correction to the abnormal representation allowing for largely normal perception. To this end we assessed the organization patterns of early and ventral visual cortex in five albinotic, one achiasmic, and five control participants. In albinism and achiasma the mirror-symmetrical superposition of the ipsilateral and contalateral visual fields was evident not only in early visual cortex, but also in the higher areas of the ventral processing stream. Specifically, in the visual areas VO1/2 and PHC1/2 no differences in the extent, the degree of superposition, and the magnitude of the responses were evident in comparison to the early visual areas. Consequently, the highly atypical organization of the primary visual cortex was propagated downstream to highly specialized processing stages in an undiminished and unchanged manner. This indicates largely unaltered cortico-cortical connections in both types of misrouting, i.e., enhanced and reduced crossing of the optic nerves. It is concluded that main aspects of visual function are preserved despite sizable representation abnormalities in the ventral visual processing stream.

New pentacoordinated rhodium species as unexpected products during the in situ generation of dimeric diphosphine-rhodium neutral catalysts.

Dimeric rhodium complexes of the type [Rh(PP)(µ2 -Cl)]2 (PP=diphosphine) are often used as precatalysts and are generated "in situ" from the corresponding diolefin complexes by exchange of the diene with the desired diphosphine. Herein, we report that the "in situ" procedure also leads to unexpected monomeric pentacoordinated neutral complexes of the type [RhCl(PP)(diolefin)], for the first time herein characterized by NMR spectroscopy and X-ray crystallography for the ligands 1,4-bis(diphenylphosphino)propane (DPPP), 1,4-bis(diphenylphosphino)butane (DPPB), and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP). The pentacoordinated complexes are in equilibrium with the dimeric target compound [Rh(PP)(µ2 -Cl)]2 . The equilibrium is influenced by the rhodium-diolefin precursor, the solvent and the temperature. Based on the results of NMR and UV/Vis spectroscopic analysis (kinetics) it could be shown that the pentacoordinated complex [RhCl(PP)(diolefin)] may arise both from the "in situ"-generated neutral complex [Rh(PP)(µ2 -Cl)] by reaction with the free diolefin and, more surprisingly, directly from [Rh(diolefin)(µ2 -Cl)]2 and the diphosphine.