Scalable Synthesis of Piperazines Enabled by Visible‐Light Irradiation and Aluminum Organometallics

The development of more active C? H oxidation catalysts has inspired a rapid, scalable, and stereoselective assembly of multifunctional piperazines through a [3+3] coupling of azomethine ylides. A combination of visible‐light irradiation and aluminum organometallics is essential to promote this transformation, which introduces visible‐light photochemistry of main‐group organometallics and sets the basis for new and promising catalysts.     

Synthesis of Indolophanes by Photochemical Macrocyclization

Herein, we report the synthetically practical, short, and general access to novel indolophane architectures by means of a photochemical C?H activation process—the Witkop cyclization. These highly strained scaffolds were obtained by photoinduced ring closure and feature atropisomerism as well as aromatic ring current effects, which both have been investigated. The prevailing regioselectivity of theWitkop cyclization reaction was completely reversed by the presence of a quaternary carbon center, exerting a strong Thorpe–Ingold effect on the system for which experimental‐evidence is provided.     

Catalytic C1 Alkylation with Methanol and Isotope‐Labeled Methanol

A metal‐catalyzed methylation process has been developed. By employing an air‐ and moisture‐stable manganese catalyst together with isotopically labeled methanol, a series of D‐, CD₃‐, and ¹³C‐labeled products were obtained in good yields under mild reaction conditions with water as the only byproduct.     

A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones

Enzymatic core components from trans‐acyltransferase polyketide synthases (trans‐AT PKSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds. Here we focus on a group of oxygenases identified in various trans‐AT PKS pathways, including those for pederin, oocydins, and toblerols. Using the oocydin pathway homologue (OocK) from Serratia plymuthica 4Rx13 and N‐acetylcysteamine (SNAC) thioesters as test surrogates for acyl carrier protein (ACP)‐tethered intermediates, we show that the enzyme inserts oxygen into β‐ketoacyl moieties to yield malonyl ester SNAC products. Based on these data and the identification of a non‐hydrolyzed oocydin congener with retained ester moiety, we propose a unified biosynthetic pathway of oocydins, haterumalides, and biselides. By providing access to internal ester, carboxylate pseudostarter, and terminal hydroxyl functions, oxygen insertion into polyketide backbones greatly expands the biosynthetic scope of PKSs.     

Inhibitors of the kinase IspE: structure-activity relationships and co-crystal structure analysis

Enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are therapeutic targets for the treatment of important infectious diseases. Whereas this pathway is absent in humans, it is used by plants, many eubacteria and apicomplexan protozoa, including major human pathogens such as Plasmodium falciparum and Mycobacterium tuberculosis. Herein, we report on the design, preparation and biological evaluation of a new series of ligands for IspE protein, a kinase from this pathway. These inhibitors were developed for the inhibition of IspE from Escherichia coli, using structure-based design approaches. Structure-activity relationships (SARs) and a co-crystal structure of Aquifex aeolicus IspE bound to a representative inhibitor validate the proposed binding mode. The crystal structure shows that the ligand binds in the substrate-rather than the adenosine 5'-triphosphate (ATP)-binding pocket. As predicted, a cyclopropyl substituent occupies a small cavity not used by the substrate. The optimal volume occupancy of this cavity is explored in detail. In the co-crystal structure, a diphosphate anion binds to the Gly-rich loop, which normally accepts the triphosphate moiety of ATP. This structure provides useful insights for future structure-based developments of inhibitors for the parasite enzymes.     

In-line application of electric field in capillary separation systems: Joule heating, pH and conductivity

This study concerns the technique electric field-assisted capillary liquid chromatography. In this technique, an electric field is applied over the separation capillary in order to provide an additional selectivity. In this technique, the electric field is applied in-line in the separation capillary and here the electric current is the factor limiting the magnitude of applied electric field. The influence of Joule heating and other factors on the current in such systems has been investigated. The temperature in the capillary was first measured within a standard CE set-up, as function of effect per unit of length. Then the same cooling system was applied to an in-line set-up, to replicate the conditions between the two systems, and thus the temperature. Thus Joule heating effects could then be calculated within the in-line system. It was found that for systems applying an electric field in line, the direct influence from Joule heating was only relatively small. The pH in the capillary was measured in the in-line set-up using cresol red/TRIS solutions as pH probe. Significant changes in pH were observed and the results suggested that electrolysis of water is the dominant electrode reaction in the in-line system. In summary, the observed conductivity change in in-line systems was found to be mainly due to the pH change by hydrolysis of water, but primarily not due the temperature change in the capillary column.     

Accumulation and filtering of nanoparticles in microchannels using electrohydrodynamically induced vortical flows

We present an approach for the accumulation and filtering of nano- and microparticles in microfluidic devices that is based on the generation of electric traveling waves in the radio-frequency range. Upon application of the electric field via a microelectrode array, complex particle trajectories and particle accumulation are observed in well-defined regions in a microchannel. Through the quantitative mapping of the 3-D flow pattern using two-focus fluorescence cross-correlation spectroscopy, two vortices could be identified as one of the sources of the force field that induces the formation of particle clouds. Dielectrophoretic forces that directly act on the particles are the second source of the force field. A thorough 2-D finite element analysis identifies the electric traveling wave mechanism as the cause for the unexpected flow behavior observed. Based on these findings, strategies are discussed, first, for avoiding the vortices to optimize electrohydrodynamic micropumps and, secondly, for utilizing the vortices in the development of microdevices for efficient particle accumulation, separation, and filtering. Such devices may find numerous biomedical applications when highly diluted nano- and microsuspensions have to be processed.     

Thermodynamics and bending energetics of toruslike micelles

The self-assembly of surfactants forming toruslike or toroidal micelles has been investigated from a theoretical point of view, in particular the structural behaviour and stability of tori in terms of the three bending elasticity constants spontaneous curvature (H(0)), bending rigidity (k(c)) and saddle-splay constant (k(c)). It is demonstrated that the size of toruslike micelles increases with an increasing bending rigidity, but is independent of both spontaneous curvature and saddle-splay constant. Similar to conventional micelles, toruslike micelles are found to be stable over bilayers as the spontaneous curvature times the surfactant layer thickness exceeds 1/4. Moreover, it is shown that toruslike micelles, in general, are favoured at the expense of long spherocylindrical micelles as a result of elimination of the unfavourable end-caps. However, conventional micelles that are able to grow with respect to both width and length (tablets) may be stable over tori as well as spheres in much wider regimes of different bending elasticity constants. As a result, toruslike micelles are predicted to be stable over conventional micelles, including rods, at large values of the effective bending constant k(eff) identical with 2k(c)+k(c), i.e. in the same region where infinite cylinders are expected to be observed. This result is consistent with the fact that toruslike micelles have usually been observed to coexist with large networks of branched cylinders.     

Bonding situations in tricoordinated beryllium phenyl complexes

The bonding situation in the tricoordinated beryllium phenyl complexes [BePh₃]⁻, [(pyridine)BePh₂] and [(trimethylsilyl-N-heterocyclic imine)BePh₂] is investigated experimentally and computationally. Comparison of the NMR spectroscopic properties of these complexes and of their structural parameters, which were determined by single crystal X-ray diffraction experiments, indicates the presence of π-interactions. Topology analysis of the electron density reveals elliptical electron density distributions at the bond critical points and the double bond character of the beryllium-element bonds is verified by energy decomposition analysis with the combination of natural orbital for chemical valence. The present beryllium-element bonds are highly polarized and the ligands around the central atom have a strong influence on the degree of π-delocalization. These results are compared to related triarylboranes.