Quantitative aspects of analyzing small molecules – monitoring singly or doubly charged ions? A case study of ximelagatran

Precision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]²⁺ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]²⁺ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]²⁺ ion is more inclined to undergo fragmentation than [Xi + H]⁺. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low‐mass product ions. Copyright © 2010 John Wiley & Sons, Ltd.     

Dissociative and molecular oxygen chemisorption channels on reduced rutile TiO2(110): An STM and TPD study

High-resolution scanning tunneling microscopy (STM) and temperature-programmed desorption (TPD) were used to study the interaction of O₂ with reduced TiO₂(110)–(1 × 1) crystals. STM is the technique of choice to unravel the relation between vacancy and non-vacancy assisted O₂ dissociation channels as a function of temperature. It is revealed that the vacancy-assisted, first O₂ dissociation channel is preferred at low temperature (~ 120 K), whereas the non-vacancy assisted, second O₂ dissociation channel operates at temperatures higher than 150 K–180 K. Based on the STM results on the two dissociative O₂ interaction channels and the TPD data, a new comprehensive model of the O₂ chemisorption on reduced TiO₂(110) is proposed. The model explains the relations between the two dissociative and the molecular O₂ interaction channels. The experimental data are interpreted by considering the available charge in the near-surface region of reduced TiO₂(110) crystals, the kinetics of the two O₂ dissociation channels as well as the kinetics of the diffusion and reaction of Ti interstitials.     

Oligocarbamate molecular transporters: design,synthesis, and biological evaluation of a new class of transporters for drug delivery

Molecular transporters have the ability to deliver drugs and probe molecules into cells and tissues irrespective of their physical properties. We now report the design, synthesis, and biological evaluation of a new family of molecular transporters, guanidinylated oligocarbamates that enable exceptionally efficient uptake into cells and tissues. The synthesis features a solid-phase stepwise oligomerization to obtain the oligocarbamates and a single step perguanidinylation for the facile introduction of up to nine guanidinium groups. The oligocarbamate 9-mer is found to be among the most efficient transporters known, entering cells faster than even d-Arg9 and HIV-1 Tat49-57. Significantly, this new family of transporters also enables uptake into the formidable skin barrier of a probe molecule that by itself does not penetrate skin.     

Universality class of criticality in the restricted primitive model electrolyte

The 1:1 equisized hard-sphere electrolyte or restricted primitive model has been simulated via grand-canonical fine-discretization Monte Carlo. Newly devised unbiased finite-size extrapolation methods using loci in the temperature-density or (T,rho) plane of isothermal rho(2-k) vs pressure inflections, of Q identical with(2)/ maxima, and of canonical and C(V) criticality, yield estimates of (T(c),rho(c)) to +/-(0.04,3)%. Extrapolated exponents and Q ratio are (gamma,nu,Q(c)) = [1.24(3), 0.63(3); 0.624(2)], which support Ising (n = 1) behavior with (1.23(9), 0.630(3); 0.623(6)), but exclude classical, XY (n = 2), self-avoiding walk (n = 0), and n = 1 criticality with potentials varphi(r)>Phi/r(4.9) when r-->infinity.     

A multigrid method with unstructured adaptive grids for steady Euler equations

The multigrid method based on multi-stage Jacobi relaxation, earlier developed by the authors for structured grid calculations with Euler equations, is extended to unstructured grid applications. The meshes are generated with Delaunay triangulation algorithms and are adapted to the flow solution.     

Tabu search for graph partitioning

In this paper, we develop a tabu search procedure for solving the uniform graph partitioning problem. Tabu search, an abstract heuristic search method, has been shown to have promise in solving several NP-hard problems, such as job shop and flow shop scheduling, vehicle routing, quadratic assignment, and maximum satisfiability. We compare tabu search to other heuristic procedures for graph partitioning, and demonstrate that tabu search is superior to other solution approaches for the uniform graph partitioning problem both with respect to solution quality and computational requirements.     

CH,CD, CC and HH coupling constants in isotopically enriched cyclobutene

¹H, ²H and ¹³C NMR studies of cyclobutene and a series of isotopically enriched species have led to a determination of the ¹H? ¹H, ¹³C? ¹H, ¹³C? ²H and ¹³C? ¹³C coupling constants in these compounds. In agreement with general observations, ¹J(CH) is found to depend on the hybridization of the carbon atoms. Likewise, ²J(HH), ²J(CC), ³J(HH) and ³J(CH), but not ²J(CH), depend on the angles between the bonds connecting the coupled nuclei. When comparing cyclobutene with thiete 1,1-dioxide (thiete sulphone) an increase of almost 20 Hz is observed for ¹J(C-2, H-2) in the latter compound. All but one of the observed deuterium isotope effects on chemical shifts are negative. In the case of isotope effects upon the one-bond coupling constants, the obtained values support the results of the theoretical calculations of Sergeev and Solkan.     

On the time dependent behaviour of the truncated birth-death process

Conditions are obtained for the truncated birth-death process to be stochastically monotone in the long run.