Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types

There is intense interest in late‐stage catalytic C?H bond functionalization as an integral part of synthesis. Effective catalysts must have a broad substrate range and tolerate diverse functional groups. Drug molecules provide a good test of these attributes of a catalyst. A library of P450_BM3 mutants developed from four base mutants with high activity for hydrocarbon oxidation produced human metabolites of a panel of drugs that included neutral (chlorzoxazone, testosterone), cationic (amitriptyline, lidocaine) and anionic (diclofenac, naproxen) compounds. No single mutant was active for all the tested drugs but multiple variants in the library showed high activity with each compound. The high conversions enabled full product characterization that led to the discovery of the new P450 reaction type of oxidative decarboxylation of an α‐hydroxy carboxylic acid and the formation a protected imine from an amine, offering a novel route to α‐functionalization of amines. The substrate range and varied product profiles suggest that this library of enzymes is a good basis for developing late‐stage C?H activation catalysts.     

Synchrotron X‐ray CT characterization of titanium parts fabricated by additive manufacturing. Part II. Defects

Synchrotron X‐ray tomography (SXRT) has been applied to the study of defects within three‐dimensional printed titanium parts. These parts were made using the Arcam EBM^® (electron beam melting) process which uses powdered titanium alloy, Ti64 (Ti alloy with approximately 6%Al and 4%V) as the feed and an electron beam for the sintering/welding. The experiment was conducted on the Imaging and Medical Beamline of the Australian Synchrotron. The samples represent a selection of complex shapes with a variety of internal morphologies. Inspection via SXRT has revealed a number of defects which may not otherwise have been seen. The location and nature of such defects combined with detailed knowledge of the process conditions can contribute to understanding the interplay between design and manufacturing strategy. This fundamental understanding may subsequently be incorporated into process modelling, prediction of properties and the development of robust methodologies for the production of defect‐free parts.     

Edge of chaos in a parallel shear flow

We study the transition between laminar and turbulent states in a Galerkin representation of a parallel shear flow, where a stable laminar flow and a transient turbulent flow state coexist. The regions of initial conditions where the lifetimes show strong fluctuations and a sensitive dependence on initial conditions are separated from the ones with a smooth variation of lifetimes by an object in phase space which we call the "edge of chaos." We describe techniques to identify and follow the edge, and our results indicate that the edge is a surface. For low Reynolds numbers we find that the surface coincides with the stable manifold of a periodic orbit, whereas at higher Reynolds numbers it is the stable set of a higher-dimensional chaotic object.     

Charge density waves in PbTe in strong magnetic fields

It is found that in a strong magnetic field the parameters of PbTe allow for a Peierls-type transition at a few degrees Kelvin.