The mean size of the gold (Au) core in the synthesis of
dodecanethiolate-stabilized Au cluster compounds
can be finely adjusted by choice of the Au:dodecanethiolate ratio and
the temperature and rate at which
the reduction is conducted. The Au clusters have been examined
with a large number of independent
analytical tools, producing a remarkably consistent picture of these
materials. Average cluster and core
dimensions, as ascertained by 1H NMR line broadening,
high-resolution transmission electron microscopy,
small-angle X-ray scattering, and thermogravimetric analysis, vary
between diameters of 1.5 and 5.2 nm
(∼110−4800 Au atoms/core). The electronic properties of the Au
core were examined by UV/vis and X-ray
photoelectron spectroscopy; the core appears to remain largely metallic
in nature even at the smallest core
sizes examined. The alkanethiolate monolayer stabilizing the Au
core ranges with core size from ∼53 to
nearly 520 ligands/core, and was probed by Fourier transform infrared
spectroscopy, differential scanning
calorimetry, contact-angle measurements, and thermal desorption mass
spectrometry. The dodecanethiolate
monolayer on small and large core clusters exhibits discernable
differences; the line dividing “3-dimensional”
monolayers and those resembling self-assembled monolayers on flat Au
(2-dimensional monolayers) occurs
at clusters with ∼4.4 nm core diameters.
Self-evidently, research in areas supporting "systems biology" such as genomics, proteomics, and metabonomics are critically dependent on the generation of sound analytical data. Metabolic phenotyping using LC-MS-based methods is currently at a relatively early stage of development, and approaches to ensure data quality are still developing. As part of studies on the application of LC-MS in metabonomics, the within-day reproducibility of LC-MS, with both positive and negative electrospray ionization (ESI), has been investigated using a standard "quality control" (QC) sample. The results showed that the first few injections on the system were not representative, and should be discarded, and that reproducibility was critically dependent on signal intensity. On the basis of these findings, an analytical protocol for the metabonomic analysis of human urine has been developed with proposed acceptance criteria based on a step-by-step assessment of the data. Short-term sample stability for human urine was also assessed. Samples were stable for at least 20 h at 4 degrees C in the autosampler while queuing for analysis. Samples stored at either -20 or -80 degrees C for up to 1 month were indistinguishable on subsequent LC-MS analysis. Overall, by careful monitoring of the QC data, it is possible to demonstrate that the "within-day" reproducibility of LC-MS is sufficient to ensure data quality in global metabolic profiling applications.
Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of (3)H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures.
In the field of metabonomics, 1H NMR and full scan mass spectrometry methods have usually been combined with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to detect patterns in biofluids that correspond to specific effects, usually a toxic site effect of a compound. Confounders together with great interindividual variation complicate such analysis in humans, and therefore, metabonomic data are almost restricted to animals. In our study, a constant neutral loss (CNL) scan on a linear ion trap demonstrated increased sensitivity and specificity compared to a full scan approach and was performed to detect mercapturic acids (MA), a class of effect markers. The method was applied to human volunteers administered 50 and 500 mg of acetaminophen (AAP), a model compound known to form MAs. Using a new algorithm to prepare the CNL data for chemometrics, discrimination of control and postdose samples could be performed using PCA and PLS-DA. The loadings plots clearly revealed AAP-MA as a marker, even at low-dose levels. Orthogonal signal correction (OSC) was carried out to investigate background information that is not due to exposure. Surprisingly, the OSC data provided a classification of male and female subjects showing the performance of the new approach.
A hybrid quadrupole orthogonal time-of-flight mass spectrometer optimized for MALDI and electrospray ionization has been equipped with a C 60 cluster ion source. This configuration is shown to exhibit a number of characteristics that improve the performance of traditional time-of-flight secondary ion mass spectrometry (SIMS) experiments for the analysis of complex organic materials, and potentially, for chemical imaging. Specifically, the primary ion beam is operated as a continuous rather than a pulsed beam, resulting in up to 4 orders of magnitude greater ion fluence on the target. The secondary ions are extracted at very low voltage into 8 millitorr of N 2 gas introduced for collisional focusing and cooling purposes. This extraction configuration is shown to yield secondary ions that rapidly lose memory of the mechanism of their birth, yielding tandem mass spectra that are identical for SIMS and MALDI. With implementation of ion trapping, the extraction efficiency is shown to be equivalent to that found in traditional TOF-SIMS machines. Examples are given, for a variety of substrates that illustrate mass resolution of 12,000-15,600 with mass range for inorganic compounds to m/z 40,000. Preliminary chemical mapping experiments show that with added sensitivity, imaging in the MS/MS mode of operation is straightforward. In general, the combination of MALDI and SIMS is shown to add capabilities to each technique, providing a robust platform for TOF-SIMS experiments that already exists in a large number of laboratories.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.