The synthesis of various new trialkylhydroxylamines is described. The rate constant of the C-O bond cleavage of these new alkoxyamines has been measured. For example, C-O bond homolysis rates in a series of para-substituted TEMPO-styryl compounds TEMPO-CH(CH3)C6H5X 1a (p-MeO), 1b (p-Me), 1d (p-H), 1e (p-Br), and 1f (p-MeO2C) are presented. Furthermore, rate constants for the C-O bond cleavage of alpha-heteroaryl-substituted secondary alkoxyamines are discussed. A correlation by which the rate constant for the C-O bond cleavage of TEMPO-derived alkoxyamines can be predicted from the C-H BDEs of the corresponding alkanes is presented. Solvent effects as well as the effect of camphorsulfonic acid on the rate of the C-O bond homolysis are discussed. Finally, EPR and kinetic evidence show that alkoxyamines derived from nitroxides which are capable of intramolecular H-bonding undergo C-O bond cleavage faster than the corresponding non-H-bond-forming analogues.

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a microplate enzyme assay with Ellman's reagent. This permitted the isolation of the alkaloids taspine (1) and (−)-asimilobine (2), which were detected for the first time in this species. Compound 1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited the enzyme in a long-lasting and concentration-dependent fashion with an IC 50 value of 0.33 ± 0.07 μM. Extensive molecular docking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalize the binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared to galanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1-AChE complex was found to be stabilized by (i) sandwich-like π-stacking interactions between the planar aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.The enzyme acetylcholinesterase (AChE; EC 3.1.1.7) plays a central role in cholinergic brain synapses and neuromuscular junctions. Its major role is the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). According to the cholinergic hypothesis, 1 the selective and irreversible deficiency of cholinergic functions leads to memory impairment. The direct correlation of cholinergic deficit and the severity of dementia, e.g., in patients suffering from Alzheimer's disease (AD) and other related diseases, is why these forms of memory impairment are treated symptomatically with AChE inhibitors (AChEIs). As knowledge of the mechanisms responsible for neurodegeneration in AD increases, it is anticipated that neuroprotective drugs will be developed to complement current symptomatic treatments. Research has shown a direct link between cholinergic impairment and altered amyloid precursor protein (APP) processing as a major pathogenetic

We analyze the effects of captive offshoring of innovation activities on the ability of the firms to adapt their organizational structures. Basing our arguments on complexity theory, we use three consecutive waves of the German part of the Community Innovation Survey to test our hypotheses. We find an inverted u-shape of innovation offshoring on the effectiveness of organizational adaptability, implying an optimal threshold value of innovation offshoring. This value is 11% for share of offshored R&D, 15% for downstream innovation activities such as local market adaptation, and 34% for design activities. We also analyze several contingency variables. In particular, we show that the costs of innovation offshoring in terms of reduced organizational adaptation are increased by a regional dispersion of the offshoring activities and strong embeddedness in onshore networks. We also show that smaller firms find it easier to deal with the management complexity induced by geographical dispersion of innovation activities.

We develop a behavioural framework of bounded rational decision-making under uncertainty to analyse the role of technological dynamism in the firm’s environment for its decision to internationalise innovation. Applying prospect theory, we argue that technological uncertainty in the firm’s environment affects its risk preferences differently depending on its technological capabilities. A key prediction is that firms with low capabilities will internationalise innovation when faced by technological uncertainty while firms with high capabilities will concentrate their innovation at the home-base. We also argue that our behavioural approach based on prospect theory is not a stand-alone programme but benefits from the integration with traditional concepts in IB. In particular, we make a case that organisational measures fostering absorptive capacity, such as intensive personnel exchange between headquarters and subsidiaries, can help to attenuate the high-capability firms’ tendency to concentrate innovation at the home-base when faced by high uncertainty. We corroborate the predictions of our framework based on data from the German part of the Community Innovation Survey