Johan Johansson

Sequential One-Pot Ruthenium-Catalyzed Azide-Alkyne Cycloaddition from Primary Alkyl Halides and Sodium Azide

An experimentally simple sequential one-pot RuAAC reaction, affording 1,5-disubstituted 1H-1,2,3-triazoles in good to excellent yields starting from an alkyl halide, sodium azide, and an alkyne, is reported. The organic azide is formed in situ by treating the primary alkyl halide with sodium azide in DMA under microwave heating. Subsequent addition of [RuClCp*(PPh(3))(2)] and the alkyne yielded the desired cycloaddition product after further microwave irradiation.

Sniffing out early reaction intermediates

Powerful tools for identifying reaction intermediates and by-products of chemical reactions are crucial for the development of high-yield chemical syntheses, not only for testing theoretical mechanistic models and calculations, but also to obtain improved understanding of reaction mechanisms during trial experiments. This will enable more efficient steering toward optimum yields for a variety of practical synthetic applications. With more demanding challenges regarding synthetic yields, for example for the production of larger and more sophisticated pharmaceuticals, efficient analytical tools become increasingly more important. NMR is one of the most powerful techniques for studying reaction mechanisms in organic reactions, but mass spectrometric tests on the reaction mixture can often be a good complement to time-consuming NMR experiments. The incorporation of a high-resolution mass spectrometry technique and the use of a custom-made desorption electrospray ionization (DESI) source as reported by Zare and others (1, 2) offer a remarkably increased ability to identify ions directly, because they are formed in a liquid-phase chemical reaction.

Optimization of ketone-based P2Y12 receptor antagonists as antithrombotic agents: Pharmacodynamics and receptor kinetics considerations

Modification of a series of P2Y12 receptor antagonists by replacement of the ester functionality was aimed at minimizing the risk of in vivo metabolic instability and pharmacokinetic variability. The resulting ketones were then optimized for their P2Y12 antagonistic and anticoagulation effects in combination with their physicochemical and absorption profiles. The most promising compound showed very potent antiplatelet action in vivo. However, pharmacodynamic-pharmacokinetic analysis did not reveal a significant separation between its anti-platelet and bleeding effects. The relevance of receptor binding kinetics to the in vivo profile is described.

Bridging ligand length controls at selectivity and enantioselectivity of binuclear ruthenium threading intercalators.

The slow dissociation of DNA threading intercalators makes them interesting as model compounds in the search for new DNA targeting drugs, as there appears to be a correlation between slow dissociation and biological activity. Thus, it would be of great value to understand the mechanisms controlling threading intercalation, and for this purpose we have investigated how the length of the bridging ligand of binuclear ruthenium threading intercalators affects their DNA binding properties. We have synthesised a new binuclear ruthenium threading intercalator with slower dissociation kinetics from ct-DNA than has ever been observed for any ruthenium complex with any type of DNA, a property that we attribute to the increased distance between the ruthenium centres of the new complex. By comparison with previously studied ruthenium complexes, we further conclude that elongation of the bridging ligand reduces the sensitivity of the threading interaction to DNA flexibility, resulting in a decreased AT selectivity for the new complex. We also find that the length of the bridging ligand affects the enantioselectivity with increasing preference for the ΔΔ enantiomer as the bridging ligand becomes longer.

Conformational properties of 1,4- and 1,5-substituted 1,2,3-triazole amino acids-building units for peptidic foldamers

Conformational diversity of 1,4- and 1,5-substituted 1,2,3-triazole amino acids makes them promising building units for novel peptidic foldamers.

Towards Artificial Photosynthesis of CO2‐Neutral Fuel: Homogenous Catalysis of CO2‐Selective Reduction to Methanol Initiated by Visible‐Light‐Driven Multi‐Electron Collector

B.N. was supported by grants from the King Abdullah University of Science and Technology (KAUST). Y.N. holds a KAUST postdoctoral fellowship.

Covalent functionalization of carbon nanotube forests grown in situ on a metal-silicon chip

We report on the successful covalent functionalization of carbon nanotube (CNT) forests, in situ grown on a silicon chip with thin metal contact film as the buffer layer between the CNT forests and the substrate. The CNT forests were successfully functionalized with active amine and azide groups, which can be used for further chemical reactions. The morphology of the CNT forests was maintained after the functionalization. We thus provide a promising foundation for a miniaturized biosensor arrays system that can be easily integrated with Complementary Metal-Oxide Semiconductor (CMOS) technology.

Generation of a functional humanized Delta-like ligand 4 transgenic mouse model

Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form. However, KIKO strategies can fail to generate homozygous mice, even though the human form is expressed and the endogenous mouse locus is correctly targeted. A typical strategy for generating KIKO mice is by ATG fusion where the human cDNA is inserted downstream of the endogenous mouse promoter elements. However, when adopting this strategy it is possible that the mouse promoter fails to express the human form in a manner compensating for loss of the mouse form or alternatively the human protein is incompatible in the context of the mouse pathway being investigated. So to understand more around the biology of KIKO models, and to overcome our failure with a number of ATG fusion strategies, we developed a range of humanized models focused on Delta-like 4 (Dll4), a target where we initially failed to generate a humanized model. By adopting a broader biologic strategy, we successfully generated a humanized DLL4 KIKO which led to a greater understanding of critical biological aspects for consideration when developing humanized models.

Incentive Schemes and Female Leadership in Financial Firms

Purpose: To explore how performance in Swedish financial companies is affected by the presence of a female chief executive officer (CEO), the presence of an incentive scheme, and the proportion of female board members. Design/methodology/approach: Our sample consists of data from the last 10 years of all the 43 companies within GICS 40 listed at the Swedish stock exchange OMX Stockholm. We used multiple regressions to explore the association between the explanatory and firm performance variables. Findings: The results indicate that a female CEO is associated with a lower return on equity (ROE) and a lower Tobin’s Q, but we find no significant association between the proportion of female board members and firm performance. An incentive scheme is generally associated with a lower return on assets (ROA) and a higher Tobin’s Q. In particular, a share-based incentive scheme is associated with a lower ROA, a lower ROE, and a higher Tobin’s Q. Originality/value: To the authors’ knowledge, this is the first paper to analyse governance in financial firms with respect to female leadership as well as to incentive schemes. We conclude that governance structures in financial firms need to balance accounting-based and market-based performance. A large focus on share prices, especially at a certain time, may create short-term effects that need not necessarily be optimal in the long run for shareholders.