Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin

Unsymmetrical dispiro- and spirotetraoxanes have been designed and synthesized via acid-catalyzed cyclocondensation of bis(hydroperoxides) with ketones. Incorporation of water-soluble and polar functionalities, via reductive amination and amide bond formation, produces several analogues with low nanomolar in vitro antimalarial activity. Several analogues display an unprecedented level of oral antimalarial activity for this class of endoperoxide drug.     

Double-Mannich annulation of cyclic ketones using N,N-Bis(ethoxymethyl)alkylamine reagents

[Structure: see text] N,N-Bis(ethoxymethyl)alkylamines function as effective reagents in the double-Mannich annulation of cyclic ketone substrates, providing efficient access to a series of azabicyclic ketones. These ring systems are a useful scaffold for the four-step synthesis of novel constrained homocholine analogues.     

Purification of drugs from biological fluids by counter-current chromatography

Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.     

C−H Functionalization of Commodity Polymers

Synthetic manipulation of polymer substrates is one of the oldest and most reliable methods to increase the functional diversity of soft materials. Modifying the chemical structure of polymers that are already produced on a commodity scale leverages the current high‐volume and low‐cost production of commodity plastics for the discovery of modern materials. A myriad of polymer C?H functionalization methods have been developed which enable the modification of material properties on both a laboratory and industrial scale. More recently, driven by advances in C?H activation, photoredox catalysis, and radical chemistry, chemoselective approaches have emerged as a means to impart precise functionality onto commodity polymer substrates. This Review discusses the historical significance of and contemporary advances in the C?H functionalization of commodity polymers. The conceptual approach outlined herein presents exciting new directions for the field, including increasing the value of otherwise pervasive materials, uncovering entirely new material properties, and a viable path to upcycle post‐consumer plastic waste.     

Locus-specific brackets for reliable typing of Y-chromosome short tandem repeat markers

Short tandem repeat (STR) loci, widely used as genetic markers in disease diagnostic studies and human identity applications, are traditionally genotyped through comparison of allele sizes to a sequenced allelic ladder. Allelic ladders permit a floating bin allele calling method to be utilized, which enables reliable allele calling across laboratories, instrument platforms, and electrophoretic conditions. Precise sizing methods for STR allele calling involving fixed bins can also be used when a high degree of precision has been demonstrated within an instrument platform and a set of electrophoretic conditions. An alternative method for reliable genotyping of STR markers, locus-specific brackets (LSBs), is introduced here. LSBs are artificial alleles created through molecular biology manipulations to be shorter or longer than alleles commonly seen in populations under investigation. The size and repeat number of measured alleles are interpolated between the two LSB products that are mixed with the polymerase chain reaction-amplified STR alleles. The advantages and limitations of the LSB approach are described along with a concordance study between the LSB typing approach and other STR typing methods. Complete agreement was observed with 162 samples studied at 5 Y-chromosome loci.     

Isotopic fractionation of endogenous anabolic androgenic steroids and its relationship to doping control in sports

The use of gas chromatography (GC)-combustion (C)-isotope ratio mass spectrometry (IRMS) demonstrates that a single oral administration of dehydroepiandrosterone (DHEA, 100 mg) to a male subject significantly lowers the 13C content of etiocholanolone (Et) and androsterone (A) in the subject's urine. The difference in carbon isotope ratio (d13C per thousand) values between Et and A increases from 1.6 per thousand at the time of administration to 5.1 per thousand at 26 h post-administration, indicating preferential metabolism of administered DHEA to form Et in relation to A. Multiple oral administrations of DHEA to a male subject reveals lower d13C values during the excretion period of Et (-31.7 per thousand to -34.6 per thousand) and A (-31.4 per thousand to -33.0 per thousand) to that of the d13C value of the administered DHEA (-31.3 per thousand). Reference distributions of d13C Et and d13C A constructed from normal athlete populations within Australia and New Zealand show a small natural discrimination against 13C in the formation of Et relative to A (mean=0.3 per thousand, n=167, p=0.007). Amplified differences between d13C Et and d13C A, and in vivo 13C depletion measured by GC-C-IRMS are shown to be potentially useful for doping control.     

Screening method for polycyclic aromatic hydrocarbons in soil using hollow fiber membrane solvent microextraction

A fast, inexpensive screening method for polycyclic aromatic hydrocarbons in soil has been developed. Using hollow fiber membrane solvent microextraction, 8 microl of octane extraction solvent was placed inside a porous, polypropylene fiber. Following an 8 min analyte preconcentration step, 4 microl of extract was injected into a gas chromatograph. Separation was achieved in less than 10 min with a detection limit of 0.13 mg/kg for 2-methylnaphthalene. Results of both spiked and real soil samples are presented.     

Finite-field method calculations. III. Dipole moment gradients,polarisability gradients and field-induced shifts in bond lengths,vibrational levels,

In this paper, the finite-field method is applied in calculating polarisabilities and, by extension, polarisability gradients. The method is also used to examine the shifts in a number of properties induced by electric fields of given strength. Model calculations at the SCF and Cl levels are reported for LiH. Estimates of the Raman scattering intensity and depolarisation ratio, obtained from the calculated polarisability gradient components, are presented. The dipole moment gradient, which is related to the infrared absorption intensity, is also reported. The properties for which field-dependent shifts are given comprise bond length, vibrational levels, spectroscopic constants, harmonic force constant, first anharmonic constant and dipole moment gradient.