Bioanalytical challenges for analytical chemists

Analytical chemistry contributes significantly to the life sciences through developing measurement techniques that provide quantitative chemical information. Developments in biological research present new challenges for analytical chemistry and call for revolutionary methods and new thinking. Dana Spence outlines here some key and unique challenges encountered when making measurements on samples of a biological nature, supported with real examples from his own research.     

Development of a functionalized xenon biosensor

NMR-based biosensors that utilize laser-polarized xenon offer potential advantages beyond current sensing technologies. These advantages include the capacity to simultaneously detect multiple analytes, the applicability to in vivo spectroscopy and imaging, and the possibility of "remote" amplified detection. Here, we present a detailed NMR characterization of the binding of a biotin-derivatized caged-xenon sensor to avidin. Binding of "functionalized" xenon to avidin leads to a change in the chemical shift of the encapsulated xenon in addition to a broadening of the resonance, both of which serve as NMR markers of ligand-target interaction. A control experiment in which the biotin-binding site of avidin was blocked with native biotin showed no such spectral changes, confirming that only specific binding, rather than nonspecific contact, between avidin and functionalized xenon leads to the effects on the xenon NMR spectrum. The exchange rate of xenon (between solution and cage) and the xenon spin-lattice relaxation rate were not changed significantly upon binding. We describe two methods for enhancing the signal from functionalized xenon by exploiting the laser-polarized xenon magnetization reservoir. We also show that the xenon chemical shifts are distinct for xenon encapsulated in different diastereomeric cage molecules. This demonstrates the potential for tuning the encapsulated xenon chemical shift, which is a key requirement for being able to multiplex the biosensor.     

Phase measurement for accurate mapping of chemical bonds in acentric space groups

Although the electron density is fundamental to the study of chemical bonding and density-functional theory, it cannot be accurately mapped experimentally for the important class of crystals lacking inversion symmetry, since structure factor phase information is normally inaccessible. We report the combination of x-ray and electron diffraction experiments for the determination of the electron density in acentric AlN, using multiple-scattering effects in convergent-beam electron diffraction to obtain sensitivity to structure factor phases, and describe a new error metric and weighting scheme for multipole refinement using combined measurements of structure factor magnitudes and phases.     

Influence of the constraint of bridgehead structure on phosphorus reactivity in the 1-phosphabicyclo[3.2.1]octane system

Nucleophiles attack the methiodide of the 3,4-benzo derivative of the title system to displace the P-methyl group in peference to the benzylic moiety. The trigonal bipyramidal intermediates (as well as a stable dioxyphosphorane) appear to undergo rapid isomerization.     

A family of difference sets

A construction is given for difference sets with parameters $\text{v =}\text{1}\text{2}\text{3}{}^{\mathrm{s+1}}\text{(3}{}^{\mathrm{s+1}}\text{? 1)}$, $\text{k =}\text{1}\text{2}\text{3}{}^{\mathrm{s}}\text{(3}{}^{\mathrm{s+1}}\text{+ 1), λ =}\text{1}\text{2}\text{3}{}^{\mathrm{s}}\text{(3}{}^{\mathrm{s}}\text{+ 1), n = 3}{}^{\mathrm{2s}}$ in certain noncyclic groups of order v. For s = 1 it is shown that the construction yields all possible difference sets with parameters (36, 15, 6, 9) in an abelian group of order 36.     

Implicitly restarted Arnoldi with purification for the shift-invert transformation

The need to determine a few eigenvalues of a large sparse generalised eigenvalue problem with positive semidefinite arises in many physical situations, for example, in a stability analysis of the discretised Navier-Stokes equation. A common technique is to apply Arnoldi's method to the shift-invert transformation, but this can suffer from numerical instabilities as is illustrated by a numerical example. In this paper, a new method that avoids instabilities is presented which is based on applying the implicitly restarted Arnoldi method with the semi-inner product and a purification step. The paper contains a rounding error analysis and ends with brief comments on some extensions.

     

Electron energy-loss spectroscopy in irradiation-sensitive rutile-GeO2

This report suggests that an electron energy-loss spectroscopy technique under low beam intensity is useful for beam-sensitive materials. High quality ‘damage-free’ Ge M₄₅ edge near-edge structure can be obtained using this method in rutile-GeO₂, which is susceptible to high-energy electron beam damage. Both experimental and theoretical results indicate that the Ge M₄₅ edge ELNES can be used to distinguish fourfold and sixfold coordinated Ge.     

Model for cold dark matter

We present a model for cold dark matter based upon continuum bound states of thee ⁺ e ^– system. These continuum bound states, referred to as photonium states to distinguish them from the well-known bound states of positronium, are shown to have cross sections and lifetime properties consistent with abundant production in the early universe and survival to the present time. Thus photonium can easily account for more than 90% of the total mass of the universe.The authors have benefitted from discussions with Charles J. Benesh. This work was supported in part by the US DOE grant no. DE-FG02-87ER40371, Division of High Energy and Nuclear Physics and by contract no. W-7405-ENG-82.