Diuretic screening in human urine by gas chromatography-mass spectrometry: use of a macroreticular acrylic copolymer for the efficient removal of the coextracted phase-transfer reagent after derivatization by direct extractive alkylation.

A simple and efficient procedure has been developed for the derivatization of diuretic agents in human urine by direct extractive alkylation and their detection by gas chromatography-mass spectrometry. The procedure is an improvement over previous extractive alkylation methods because of the development of a simple clean-up step using a macroreticular acrylic copolymer (SM-7 resin) to remove the coextracted phase-transfer reagent from the organic phase after derivatization. With 1 ml of sample the method gives detection limits in the range 10-50 ng/ml for acetazolamide, probenecid, dichlorphenamide, hydroflumethiazide, furosemide, chlorthalidone, bumetanide, hydrochlorothiazide, quinethazone, bendroflumethiazide, metolazone and cyclopenthiazide.     

Electrostatics of the point dipole and higher multipoles

It is shown that a distribution theory form for the electrostatics of point multipoles can be constructed, which reduces to the usual theory away from the position of the multipole, but in which the total electromagnetic self-energy is zero and the self-force density is zero.     

Ring opening metathesis polymerization of triazole‐bearing cyclobutenes: Diblock copolymer synthesis and evaluation of the effect of side group size on polymerization kinetics

Cyclobutenes containing pendant groups of varying sizes were polymerized via ring opening metathesis polymerization using Grubbs catalyst 2nd generation (G2). The rate of polymerization depended on the size of the pendant groups attached to the cyclobutene rings, with longer side‐chains producing slower polymerization rates and narrower molecular weight distributions. The polymerization of these new molecules proceeded with first order kinetics, consistent with a living polymerization. Chain extension experiments produced cyclobutene‐based diblock copolymers with polydispersity indices below 1.33. The synthetic methods in this report will allow the use of G2 to access new complex polymeric architectures with a higher density of pendant groups than those derived from norbornene analogs and cyclooctene moieties. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1929–1939     

The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the 4‐hydroxyandrostenedione metabolite

Studies have shown that the administration of androstenedione (ADIONE) significantly increases the urinary ratio of testosterone glucuronide to epitestosterone glucuronide (T/E) – measured by gas chromatography/mass spectrometry (GC/MS) – in subjects with a normal (≈1) or naturally high (>1) initial values. However, the urinary T/E ratio has been shown not to increase in subjects with naturally low (<1) initial values. Such cases then rely on the detection of C₆‐hydroxylated metabolites shown to be indicative of ADIONE administration. While these markers may be measured in the routine GC/MS steroid profile, their relatively low urinary excretion limits the use of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to specifically confirm ADIONE administration based on depleted ¹³C content. A mass spectrometry strategy was used in this study to identify metabolites of ADIONE with the potential to provide compound‐specific detection. C₄‐hydroxylation was subsequently shown to be a major metabolic pathway following ADIONE administration, thereby resulting in urinary excretion of 4‐hydroxyandrostenedione (4OH‐ADIONE). Complementary analysis of 4OH‐ADIONE by GC/MS and GC/C/IRMS was used to confirm ADIONE administration. Copyright © 2008 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.     

Free surface electrospinning of fibers containing microparticles

Many materials have been fabricated using electrospinning, including pharmaceutical formulations, superhydrophobic surfaces, catalysis supports, filters, and tissue engineering scaffolds. Often these materials can benefit from microparticles included within the electrospun fibers. In this work, we evaluate a high-throughput free surface electrospinning technique to prepare fibers containing microparticles. We investigate the spinnability of polyvinylpyrrolidone (PVP) solutions containing suspended polystyrene (PS) beads of 1, 3, 5, and 10 μm diameter in order to better understand free surface electrospinning of particle suspensions. PS bead suspensions with both 55 kDa PVP and 1.3 MDa PVP were spinnable at 1:10, 1:5, and 1:2 PS:PVP mass loadings for all particle sizes studied. The final average fiber diameters ranged from 0.47 to 1.2 μm and were independent of the particle size and particle loading, indicating that the fiber diameter can be smaller than the particles entrained and can furthermore be adjusted based on solution properties and electrospinning parameters, as is the case for electrospinning of solutions without particles.     

Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2

Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a Ca^II ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of Ca^II ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.     

Solvation model based on order parameters and a fast sampling method for the calculation of the solvation free energies of peptides

An analytical solvation model is proposed as a function of an order parameter, which represents the local arrangement of water molecules in the first solvation shell of peptide atoms. The model is combined with a fast sampling method, rotational isomeric state Monte Carlo, to sample efficiently the torsional degrees of freedom on a peptide backbone. This order parameter solvation model is shown to reproduce without ad hoc fitting parameters the solvation free energies of single amino acids and tripeptides with slightly better accuracy than the generalized Born model but with several orders of magnitude improvement in efficiency. This method is a potential candidate for efficiently and accurately tackling some important issues in biophysical chemistry that are related to solvation, for example, protein folding, ligand binding, etc. Our results also present fundamental new insights into solvation. Specifically, the local water geometry, represented in this work by a properly defined order parameter, carries the majority, if not all, of the energetic information of solvation, including solute-solvent interactions and solvent reorganization in the presence of the solute.     

Controlled nucleation from solution using polymer microgels

Despite its widespread occurrence in nature and broad application in industrial practice, nucleation of crystalline materials remains largely unpredictable and therefore difficult to control. In this work, we demonstrate a new method to control nucleation with polymer microgels by tuning their microstructure to vary systematically the degree of nanoscopic confinement and its effects on nucleation. We find that the polymer microstructure has a significant impact on nucleation kinetics. Moreover, there exists an optimum polymer mesh size at which the rate of nucleation is dramatically enhanced, the degree to which depends on the extent of polymer-solute interactions. With easily tunable microstructure and chemistry, polymer microgels offer a promising approach for the rational design of materials for controlling nucleation from solution.     

Application of the Floquet theory to multiple quantum NMR of dipolar-coupled multi-spin systems under magic angle spinning

A new analytical Liouville-space representation of the time-propagator under magic angle spinning (MAS) is introduced using the formalized quantum Floquet theory. This approach has the advantage that it is applicable to the analysis of any type of NMR experiment where MAS is combined with multiple-pulse excitation. General relationships describing the spectral parameters in multiple-quantum (MQ) MAS spectra are derived in this representation. Their use is illustrated with an application to double-quantum (DQ) NMR spectra of dipolar-coupled multi-spin systems. Corresponding to the separation of the MAS time-propagator into a rotor modulated and a dephasing component, two distinct mechanisms for DQ excitation are identified. One of them exploits the rotor-modulated component to excite DQ coherences through dipolar-recoupling techniques, which are familiar for spin pairs. Analytical expressions of the integral intensities and linewidths in the resulting DQ sideband pattern are derived in the form of power series expansions of the inverse rotor frequency, of which coefficients depend on structural parameters. In a multi-spin system they can most reliably be extracted in the fast spinning regime. The other mechanism exploits the dephasing component, which is characteristic to multi-spin systems only. This is shown to give rise to DQ coherences by free evolution at full rotor periods. The possibility to exploit it for selective excitation of higher order MQ coherences is discussed. In either case, the dephasing component also leads to residual broadening. The main results of the theoretical developments are demonstrated experimentally on adamantane.     

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

Background  

The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.