In Silico Design and SAR Study of Dibenzyl Trisulfide Analogues for Improved CYP1A1 Inhibition

Dibenzyl trisulfide (DTS) is a natural compound with potential cancer-preventive properties occurring in Petiveria alliacea L., an ethnomedicinal plant native to the Americas. Previous studies revealed its inhibitory activity toward cytochrome P450 (CYP)1 enzymes, key in the activation of environmental pollutants. Accordingly, the aim of this study was to design novel DTS analogues, aimed at improving not only inhibitory activity, but also specificity toward CYP1A1. This was achieved by targeting interactions with CYP1A1 residues of identified importance. Three-dimensional structures for the novel analogues were subjected to molecular docking with several CYP isoforms, before being ranked in terms of binding affinity to CYP1A1. With three hydrogen bond donors, two hydrogen bond acceptors, a molecular mass of 361 Da, and a log P of 3.72, the most promising DTS analogue obeys Lipinski's rule of five. Following synthesis and in vitro validation of its CYP1A1-inhibitory properties, this compound may be useful in future cancer-preventive approaches.     

High iso Aldehyde Selectivity in the Hydroformylation of Short‐Chain Alkenes

The hydroformylation of propene to give predominantly iso‐butanal has been achieved; class‐leading selectivity is possible even at higher temperatures that deliver fast conversion. Racemic rhodium complexes of bidentate phospholane phosphites derived from tropos‐biphenols and unusual solvent systems are the key to the selectivity observed.     

Electromagnetic Interference in Measurements of Radial Stress During Split Hopkinson Pressure Bar Experiments

Split Hopkinson pressure bar experiments on soils are often carried out using a rigid steel confining ring to provide plane strain conditions, and measurements of the circumferential strain in the ring can be used to infer the radial stress on the surface of the specimen. Previous experiments have shown evidence of irregular electromagnetic interference in measurements of radial stress, which obscures the signals and impedes analysis. The development of robust constitutive models for soils in blast and impact events relies on the accurate characterisation of this behaviour, and so it is necessary to isolate and remove the source of interference. This paper uses an induction coil to identify the source of the anomalous signals, which are found to be due to induced currents in the gauge lead wires from the movement of magnetised pressure bars (martensitic stainless steel, 440C). Comparative experiments on sand and rubber specimens are used to show that the deforming soil specimen does not make a significant contribution to this activity, and recommendations are made on reducing electromagnetic interference to provide reliable radial stress measurements.     

A Facile One Stage Synthesis of Oxazolines Under Microwave Irradiation

A rapid, high yielding procedure for the synthesis of 2-substituted oxazolines has been achieved under microwave irradiation from alkyl and aryl nitriles and β-amino alcohols using a mild Lewis acid catalyst.     

The Riemannian <Emphasis Type="Italic">L</Emphasis><Superscript>2</Superscript> topology on the manifold of Riemannian metrics

We study the manifold of all Riemannian metrics over a closed, finite-dimensional manifold. In particular, we investigate the topology on the manifold of metrics induced by the distance function of the L ² Riemannian metric—so-called because it induces an L ² topology on each tangent space. It turns out that this topology on the tangent spaces gives rise to an L ¹-type topology on the manifold of metrics itself. We study this new topology and its completion, which agrees homeomorphically with the completion of the L ² metric. We also give a user-friendly criterion for convergence (with respect to the L ² metric) in the manifold of metrics.     

Mixed‐Metal MIL‐100(Sc,M) (M=Al,Cr, Fe) for Lewis Acid Catalysis and Tandem CC Bond Formation and Alcohol Oxidation

The trivalent metal cations Al³⁺, Cr³⁺, and Fe³⁺ were each introduced, together with Sc³⁺, into MIL‐100(Sc,M) solid solutions (M=Al, Cr, Fe) by direct synthesis. The substitution has been confirmed by powder X‐ray diffraction (PXRD) and solid‐state NMR, UV/Vis, and X‐ray absorption (XAS) spectroscopy. Mixed Sc/Fe MIL‐100 samples were prepared in which part of the Fe is present as α‐Fe₂O₃ nanoparticles within the mesoporous cages of the MOF, as shown by XAS, TGA, and PXRD. The catalytic activity of the mixed‐metal catalysts in Lewis acid catalysed Friedel–Crafts additions increases with the amount of Sc present, with the attenuating effect of the second metal decreasing in the order Al>Fe>Cr. Mixed‐metal Sc,Fe materials give acceptable activity: 40 % Fe incorporation only results in a 20 % decrease in activity over the same reaction time and pure product can still be obtained and filtered off after extended reaction times. Supported α‐Fe₂O₃ nanoparticles were also active Lewis acid species, although less active than Sc³⁺ in trimer sites. The incorporation of Fe³⁺ into MIL‐100(Sc) imparts activity for oxidation catalysis and tandem catalytic processes (Lewis acid+oxidation) that make use of both catalytically active framework Sc³⁺ and Fe³⁺. A procedure for using these mixed‐metal heterogeneous catalysts has been developed for making ketones from (hetero)aromatics and a hemiacetal.