Numerical simulation of a 100-ton ANFO detonation

Shock Waves - This work describes the results from a US government-owned hydrocode (SHAMRC, Second-Order Hydrodynamic Automatic Mesh Refinement Code) that simulated an explosive detonation...     

Facile Synthesis of Lipophilic δ-Amino Acid Conjugates from 4-Alkoxy-dithionaphthoic Acids

Novel 4-alkoxy-dithionaphthoic acids were prepared and shown to be valuable synthons for δ-amino acid conjugates. These dithioacids are efficiently synthesized and purified, stable to storage, and easily derivatized to facilitate thioacylation chemistry. To this end, we have demonstrated dithionaphthoic acids (6) to successfully undergo coupling with both protected and unprotected amino acids, giving rise to stable thioamide conjugates (8 and 9).     

A Variable Tilt Smectic A Electro-Optic Effect Giving Stored Colours

A smectic A phase was aligned with a uniformly high tilt such that it appeared coloured between crossed polarisers. By applying an electric field the tilt angle of the structure increased progressively giving a Newton Spectrum series of colours. The colours remain on removal of the drive voltage.     

Rapid confirmation/quantitation of cocaine and benzoylecgonine in urine utilizing high performance liquid chromatography and tandem mass spectrometry

A rapid, but sensitive and selective method for confirmation and quantitation of benzoylecgonine (BZE) and cocaine (COC) in urine by fast-gradient liquid chromatography/tandem mass spectrometry (LC/MS/MS) is described. The chromatographic separation was performed on a reversed phase column employing fast-gradient techniques. Matrix prepared standards, blanks, and QC's were filtered then aliquots were transferred into a 96 well plate. Injection volumes of 25 microL were made onto the analytical column, with the flow diverted from the atmospheric pressure ionization source for the first 0.5 min of the analysis. Simultaneous multiple reaction monitoring (MRM) of three discrete transitions for each compound were used to identify BZE and COC. Quantitation was achieved utilizing the most prominent parent-daughter transition and internal standard calibration techniques. The coefficients of variation (CV) for the analysis of these drugs ranged from 0.6% to 6.8% at a concentration of 150 ng/mL (n = 155). This method suggests that fast-gradient LC/MS/MS may be suitable for routine confirmation of immunoassay cocaine-positive samples.     

Influence of bilayer fluctuations on the steric interactions between polymer-grafted bilayers

We propose a mechanism, through which the low membrane bending rigidity changes the steric polymer repulsion between polymer-grafted bilayers. We calculate the energy of a polymer chain trapped between two thermally undulating surfaces. The proposed treatment is in terms of de Gennes' theory of fluctuations in liquid crystals, later developed by Helfrich for membranes. We show that the confinement energy of the polymer increases due to membrane fluctuations. Also, the repulsive forces between soft polymer-grafted bilayers can extend further from the surface than the height of the polymer layer.     

Metallodrugs are unique: opportunities and challenges of discovery and development

Metals play vital roles in nutrients and medicines and provide chemical functionalities that are not accessible to purely organic compounds. At least 10 metals are essential for human life and about 46 other non-essential metals (including radionuclides) are also used in drug therapies and diagnostic agents. These include platinum drugs (in 50% of cancer chemotherapies), lithium (bipolar disorders), silver (antimicrobials), and bismuth (broad-spectrum antibiotics). While the quest for novel and better drugs is now as urgent as ever, drug discovery and development pipelines established for organic drugs and based on target identification and high-throughput screening of compound libraries are less effective when applied to metallodrugs. Metallodrugs are often prodrugs which undergo activation by ligand substitution or redox reactions, and are multi-targeting, all of which need to be considered when establishing structure–activity relationships. We focus on early-stage in vitro drug discovery, highlighting the challenges of evaluating anticancer, antimicrobial and antiviral metallo-pharmacophores in cultured cells, and identifying their targets. We highlight advances in the application of metal-specific techniques that can assist the preclinical development, including synchrotron X-ray spectro(micro)scopy, luminescence, and mass spectrometry-based methods, combined with proteomic and genomic (metallomic) approaches. A deeper understanding of the behavior of metals and metallodrugs in biological systems is not only key to the design of novel agents with unique mechanisms of action, but also to new understanding of clinically-established drugs.

The vital roles of metals in nutrients and medicines are not accessible to purely organic compounds.