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Mononuclear, coordinatively unsaturated rhenium(V) dioxo species of the type XReO2 (X = Me, substituted cyclopentadienyl) have long been postulated as intermediates in rhenium-catalyzed deoxydehydration, but their characterization was precluded because of aggregation into dimeric or oligomeric structures. Using the bulky 1,2,4-tri-tert-butylcyclopentadienyl (Cpttt) ligand, the rhenium(V) dioxo species (Cpttt)ReO2 could now be observed, in equilibrium with the dimeric form [(Cpttt)Re(O)μ-O]2, and characterized by NMR, IR, and UV-vis spectroscopies, as well as electrospray ionization mass spectrometry. (Cpttt)ReO2 is shown to be the primary product of reduction of the rhenium(VII) complex (Cpttt)ReO3 with PPh3 and demonstrated to react with ethylene glycol significantly faster than its dimeric counterpart, supporting its role as an intermediate in rhenium-catalyzed deoxydehydration reactions.

The substrate scope and the mechanism have been investigated for the MnCl2-catalyzed cross-coupling reaction between aryl halides and Grignard reagents. The transformation proceeds rapidly and in good yield when the aryl halide component is an aryl chloride containing a cyano or an ester group in the para position or a cyano group in the ortho position. A range of other substituents gave no conversion of the aryl halide or led to the formation of side products. A broader scope was observed for the Grignard reagents, where a variety of alkyl- and arylmagnesium chlorides participated in the coupling. Two radical-clock experiments were carried out, and in both cases an intermediate aryl radical was successfully trapped. The cross-coupling reaction is therefore believed to proceed by an SRN1 mechanism, with a triorganomanganate complex serving as the most likely nucleophile and single-electron donor. Other mechanistic scenarios were excluded based on the substrate scope of the aryl halide.

The substrate scope of the MnCl2-catalyzed cross-coupling between aryl halides and Grignard reagents has been extended to several methyl-substituted aryl iodides by performing the reaction at elevated temperature in a microwave oven. A radical clock experiment revealed the presence of an aryl radical as an intermediate leading to the proposal of an SRN1 pathway for the coupling. The mechanistic information gave rise to suspicion about two previously published cross-coupling reactions catalyzed by manganese(II) salts. As a result, the coupling between aryl halides and organostannanes as well as between aryl halides and amines were revisited. Both reactions were found impossible to reproduce without the addition of small amounts of palladium or copper and are therefore not believed to be catalyzed by manganese.

The present invention concerns a process for converting biomass into useful organic building blocks for the chemical industry. The process involves the use of vanadium-based catalysts of the formula Aα+a(VvXxR1yR2z)α*a-, which may be readily prepared from industrial vanadium compounds, for converting a polyol in a solvent.

The present invention concerns a process for converting biomass into useful organic building blocks for the chemical industry. The process involves the reduction of a polyol wherein at least two of the hydroxyl groups are located on adjacent carbon atoms in the presence of a molybdenum-based catalyst of the formula (I), such as (ΝΗ4)6Μo7O24⋅4Η20. A primary or secondary monohydric C1-C4 alcohol is used as reductant, as well as a solvent.

The present invention concerns a process for converting biomass into useful organic building blocks for the chemical industry. The process involves the use of molybdenum catalysts of the formula Aa+a(MovXxR1yR2zR3e)a*3-, which may be readily prepared from industrial molybdenum compounds.

The mechanism of the ruthenium-catalyzed dehydrogenative synthesis of amides from alcohols and amines was studied in detail by employing the combination of experimental and theoretical techniques. The Hammett study revealed that a small positive charge is formed at the benzylic positionin the transition state of the turnover-determining step. The value of the kinetic isotope effect of 2.290.15 indicated that the C–H bond breakage isnot the rate-determining step, but that it is one of several slow steps in the catalytic cycle. Experiments with deuterium-labeled alcohols and aminesrevealed that ruthenium-dihydride species are involved in the catalytic cycle. These experimental results were used in the dft/m06 computational studyand a plausible catalytic cycle was proposed. Both cis-dihydride and transdihydride intermediates were considered, but when the theoretical turnoverfrequencies were obtained from the calculated energies, it was found that only the trans-dihydride pathway was in agreement with the experimentallydetermined frequencies. The proposed catalytic cycle was used for an in silico search for more effective carbene ligands. The study showed that the ruthenium complexes with dimethoxyisopropylidene and pyridilidene ligands could be more active than RuCl2(IiPr)(p-cymene) used in the mechanistic investigation. Two analogs of the calculated complexes were synthesized but were not isolated in a pure form. The amidation reaction catalyzed by a mixture containing theN-ethyl pyridilidene-substituted ruthenium complex afforded the amide in 38% yield. It indicated that in silico ligand screening might be used for catalystoptimization if it is combined with a more comprehensive experimental study. An improved protocol was developed for the ruthenium-catalyzed dehydrogenative self-coupling of primary alcohols to give esters. Addition of 16.7 mol% of Mg3N2 to the reaction mixture gave esters from aliphatic alcoholsin similar yields but at lower temperature as compared with previously a reported catalytic system. This additive also suppressed the decarbonylation ofaromatic alcohols. A previously unknown ruthenium-catalyzed dehydrogenative Guerbet reaction with secondary alcohols to give ketones was discovered.The reaction conditions were optimized and the scope and the limitations were studied. It was found that only acyclic 2-methyl carbinols and simplecyclic alcohols underwent this transformation. It was shown that the reaction proceeded via the oxidation–aldol condensation–reduction pathway and thatthe active ruthenium species was a dihydride During the external stay at Haldor Topsøe A/S, the transformation of acetaldehyde over zeolite-type heterogeneous catalysts was studied. It was shown that tin-Beta zeolite was only capable of producing crotonaldehyde in low yields. Several other heterogeneous catalysts were tested (Al-Beta, Ti-Beta, Sn-MCM-41, ts-1) but none of them demonstrated substantially higher activity in the studied transformation.

Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. Using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described and compounds optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives the new analogues exhibit an equally potent anti-proliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed sub-nanomolar anti-proliferative activity towards a series of cancer cell-lines (compound 15: IC50 0.025 nM and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively), and potent anti-tumour in vivo activity in well tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumours (500 mm3) compound 15 reduced the tumour volume to one fifth of the starting volume at a dose of 3 mg/kg administered i.p., bid, day 1-9. Thus, compounds found in this study compared favourably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

The purpose of this thesis is to probe and nuance the latest Danish research in the field of self-leadership by qualifying and juxtaposing it to Weicks "Sensemaking in Organizations" and Starks theories of organized dissonance. The theoretical framework of understanding is late-modern and is in turn represented by Weick, Chia and Luhmann. Qualitative research, through interviews and observations, has expanded our knowledge and understanding of the practical implications of managing self-leadership at Politiken. Furthermore we have used our theoretical framework as the basis for the analysis of three cases, each of which has provided us with a deeper understanding of the theories' practical use in handling the complex challenges of managing the many different perspectives, performance criteria and contradictory logics that all have to coexist and come together in a synergetic and meaningful co-creation. We conclude that organizational design at Politiken is similar to that of Starks Heterachy in a number of ways, and that particularly the journalists' ability to spot new perspectives and angles is conducive in promoting new and different orders of worth. Additionally we conclude that the primary leadership challenge connected to organized dissonance is to create the necessary order to promote it. This can be done by balancing a constant scanning and reduction of complexity. We propose that a systemic and appreciative leadership style is best suited for this task. Finally we conclude that self-leadership also requires context based and individualized management in order to develop the necessary competencies and skills to have success.

Histamine receptors (HRs) are excellent drug targets for the treatment of diseases, such as schizophrenia, psychosis, depression, migraine, allergies, asthma, ulcers, and hypertension. Among them, the human H_3 histamine receptor (hH3HR) antagonists have been proposed for specific therapeutic applications, including treatment of Alzheimer’s disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity. However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity and activity for such treatments, it would be useful to have the three-dimensional structures for all four HRs. We report here the predicted structures of four HR subtypes (H_1, H_2, H_3, and H_4) using the GEnSeMBLE (GPCR ensemble of structures in membrane bilayer environment) Monte Carlo protocol, sampling ~35 million combinations of helix packings to predict the 10 most stable packings for each of the four subtypes. Then we used these 10 best protein structures with the DarwinDock Monte Carlo protocol to sample ~50 000 × 10^(20) poses to predict the optimum ligand–protein structures for various agonists and antagonists. We find that E206^(5.46) contributes most in binding H3 selective agonists in agreement with experimental mutation studies. We also find that conserved E5.46/S5.43 in both of hH_(3)HR and hH_(4)HR are involved in H_(3)/ H_(4) subtype selectivity. In addition, we find that M378^(6.55) in hH_(3)HR provides additional hydrophobic interactions different from hH_(4)HR (the corresponding amino acid of T323^(6.55) in hH_(4)HR) to provide additional subtype bias. From these studies, we developed a pharmacophore model based on our predictions for known hH_(3)HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2, PF-3654746 3, and BF2.649 (tiprolisant) 4] that suggests critical selectivity directing elements are: the basic proton interacting with D114^(3.32), the spacer, the aromatic ring substituted with the hydrophilic or lipophilic groups interacting with lipophilic pockets in transmembranes (TMs) 3–5–6 and the aliphatic ring located in TMs 2–3–7. These 3D structures for all four HRs should help guide the rational design of novel drugs for the subtype selective antagonists and agonists with reduced side effects.

A course was devised for teaching analysis and chromatography at the advanced level. Master students and ph.d. students may benefit from the learning objectives of the course. Analytical chemistry is characterised by hyphenating several types of apparatus that are designed to perform specialised unit operations. The purpose is automation of chemical analysis and chromatography that allows reliable determination of chemical species. Results of analytical chemistry form the basis of decision making that requires experience in assessment of results in terms of quality assurance. In order to obtain reliable analytical results students should combine theory of chemical reactions, experience in laboratory work and evaluation of data by means of statistics following the concepts of CDIO. The syllabus includes theory, exercise, reports and the students are examined orally. The course was attended by 30-50 students where more than 50 % found the learning objectives fullfilled but they also found the workload to be relatively high.