Optimal control of a slot car racer

In this contribution, we present a simulation method for the optimal control of a mechatronic system that is based on discrete variational calculus and apply it to compute the time-minimal path of a slot car racer. Here, the DMOC (Discrete Mechanics and Optimal Control [4]) method is used to generate offline optimal trajectories for the electro-mechanically coupled system, i.e. sequences of discrete configurations and sequences of driving voltages. The time-minimal path is achieved by the choice of different cost functions, the sum of time steps, the negative sum of the quadratic momenta and the negative sum of the quadratic velocities. Simulation results show that the momentum formulation yields the lowest number of iterations. (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A signal filtering method for improved quantification and noise discrimination in fourier transform ion cyclotron resonance mass spectrometry-based metabolomics data

Direct-infusion electrospray-ionization Fourier transform ion cyclotron resonance mass spectrometry (DI ESI FT-ICR MS) is increasingly being utilized in metabolomics, including the high sensitivity selected ion monitoring (SIM)-stitching approach. Accurate signal quantification and the discrimination of real signals from noise remain major challenges for this approach, with both adversely affected by factors including ion suppression during electrospray, ion—ion interactions in the detector cell, and thermally-induced white noise. This is particularly problematic for complex mixture analysis where hundreds of metabolites are present near the noise level. Here we address relative signal quantification and noise discrimination issues in SIM-stitched DI ESI FT-ICR MS-based metabolomics. Using liver tissue, we first optimized the number of scans (n) acquired per SIM window to address the balance between quantification accuracy versus acquisition time (and thus sample throughput); a minimum of n = 5 is recommended. Secondly, we characterized and computationally-corrected an effect whereby an ion’s intensity is dependent upon its location within a SIM window, exhibiting a 3-fold higher intensity at the high m/z end. This resulted in significantly improved quantification accuracy. Finally, we thoroughly characterized a three-stage filter to discriminate noise from real signals, which comprised a signal-to-noise-ratio (SNR) hard threshold, then a “replicate” filter (retaining only peaks in r-out-of-3 replicate analyses), and then a “sample” filter (retaining only peaks in >s% of biological samples). We document the benefits of three-stage filtering versus one- and two-stage filters, and show the importance of selecting filter parameters that balance the confidence that a signal is real versus the total number of peaks detected.     

Versatile synthesis of probes for high-throughput enzyme activity screening

Mass spectrometry based technologies are promising as generalizable high-throughput assays for enzymatic activity. In one such technology, a specialized enzyme substrate probe is presented to a biological mixture potentially exhibiting enzymatic activity, followed by an in situ enrichment step using fluorous interactions and nanostructure-initiator mass spectrometry. This technology, known as Nimzyme, shows great potential but is limited by the need to synthesize custom substrate analogs. We describe a synthetic route that simplifies the production of these probes by fashioning their perfluorinated invariant portion as an alkylating agent. This way, a wide variety of compounds can be effectively transformed into enzyme activity probes. As a proof of principle, a chloramphenicol analog synthesized according to this methodology was used to detect chloramphenicol acetyltransferase activity in cell lysate. This verifies the validity of the synthetic strategy employed and constitutes the first reported application of Nimzyme to a non-carbohydrate-active enzyme. The simplified synthetic approach presented here may help advance the application of mass spectrometry to high-throughput enzyme activity determination.

Functional plasticity and allosteric regulation of α-ketoglutarate decarboxylase in central mycobacterial metabolism

The α-ketoglutarate dehydrogenase (KDH) complex is a major regulatory point of aerobic energy metabolism. Mycobacterium tuberculosis was reported to lack KDH activity, and the putative KDH E1o component, α-ketoglutarate decarboxylase (KGD), was instead assigned as a decarboxylase or carboligase. Here, we show that this protein does in fact sustain KDH activity, as well as the additional two reactions, and these multifunctional properties are shared by the Escherichia coli homolog, SucA. We also show that the mycobacterial enzyme is finely regulated by an additional acyltransferase-like domain and by?the action of acetyl-CoA, a powerful allosteric activator able to enhance the concerted protein motions observed during catalysis. Our results uncover the functional plasticity of a crucial node in bacterial metabolism, which may be important for M. tuberculosis during host infection.     

Effect of hydrophobic nanopatches within an ionic surface on the structure of liquids

The structures of liquid water and isopropanol have been studied as a function of the size of a hydrophobic patch present in a model hydrophilic surface via molecular dynamics simulations. A significant anisotropy extending into the first few solvent layers is found over the patch which suggests implications for many real-world systems in which nanoscale heterogeneity is found.     

Engineering MIL-53(Al) flexibility by controlling amino tags

The flexibility of MIL-53(Al) can be tuned by adjusting the ratio of terephthalate and 2-amino terephthalate linkers incorporated into the framework during hydrothermal synthesis.     

Allylic C-H bond activation and functionalization mediated by tris(oxazolinyl)borato rhodium(I) and iridium(I) compounds

Allylic C-H bond oxidative addition reactions, mediated by tris(oxazolinyl)borato rhodium(I) and iridium(I) species, provide the first step in a hydrocarbon functionalization sequence. The bond activation products To(M)MH(η(3)-C(8)H(13)) (M = Rh (1), Ir (2)), To(M)MH(η(3)-C(3)H(5)) (M = Rh (3), Ir (4)), and To(M)RhH(η(3)-C(3)H(4)Ph) (5) (To(M) = tris(4,4-dimethyl-2-oxazolinyl)phenylborate) are synthesized by reaction of Tl[To(M)] and the corresponding metal olefin chloride dimers. Characterization of these group 9 allyl hydride complexes includes (1)H-(15)N heteronuclear correlation NMR experiments that reveal through-metal magnetization transfer between metal hydride and the trans-coordinated oxazoline nitrogen. Furthermore, the oxazoline (15)N NMR chemical shifts are affected by the trans ligand, with the resonances for the group trans to hydride typically downfield of those trans to η(3)-allyl and tosylamide. These group 9 oxazolinylborate compounds have been studied to develop approaches for allylic functionalization. However, this possibility is generally limited by the tendency of the allyl hydride compounds to undergo olefin reductive elimination. Reductive elimination products are formed upon addition of ligands such as CO and CN(t)Bu. Also, To(M)RhH(η(3)-C(8)H(13)) and acetic acid react to give To(M)RhH(κ(2)-O(2)CMe) (8) and cyclooctene. In contrast, treatment of To(M)RhH(η(3)-C(3)H(5)) with TsN(3) (Ts = SO(2)C(6)H(4)Me) gives the complex To(M)Rh(η(3)-C(3)H(5))NHTs (10). Interestingly, the reaction of To(M)RhH(η(3)-C(8)H(13)) and TsN(3) yields To(M)Rh(NHTs)(H)OH(2) (11) and 1,3-cyclooctadiene viaβ-hydride elimination and Rh-H bond amination. Ligand-induced reductive elimination of To(M)Rh(η(3)-C(3)H(5))NHTs provides HN(CH(2)CH=CH(2))Ts; these steps combine to give a propene C-H activation/functionalization sequence.     

Single-chain folding of polymers for catalytic systems in water

Enzymes are a source of inspiration for chemists attempting to create versatile synthetic catalysts. In order to arrive at a polymeric chain carrying catalytic units separated spatially, it is a prerequisite to fold these polymers in water into well-defined compartmentalized architectures thus creating a catalytic core. Herein, we report the synthesis, physical properties, and catalytic activity of a water-soluble segmented terpolymer in which a helical structure in the apolar core is created around a ruthenium-based catalyst. The supramolecular chirality of this catalytic system is the result of the self-assembly of benzene-1,3,5-tricarboxamide side chains, while the catalyst arises from the sequential ruthenium-catalyzed living radical polymerization of the different monomers followed by ligand exchange. The polymers exhibit a two-state folding process and show transfer hydrogenation in water.     

Scattering above energy norm of solutions of a loglog energy-supercritical Schrödinger equation with radial data

We prove global well-posedness and scattering of -solutions of the loglog energy-supercritical Schrödinger equation , 0<c<cn, n={3,4}, with radial data , . This is achieved, roughly speaking, by extending Bourgain's argument in Bourgain (1999) [1] (see also Grillakis, 2000 [5]) and Tao's argument in Tao (2005) [10] in high dimensions.