Analytica Chimica Acta: X最新文献

Perfluorinated C8-(PerfluoroC8) and bidentate anchored C8-(BDC8)-modified silica hydride stationary phases have been employed for the isocratic separation of homologous phenylalkanols and phenylalkylamines differing in their n-alkyl chain length, using aqueous-acetonitrile (ACN) mobile phases of different ACN contents from 10 to 90% (v/v) in 10% increments. These analytes showed reversed-phase (RP) retention behaviour with mobile phases of <40% (v/v) ACN content with both stationary phases but with the BDC8 stationary phase providing longer retention. The PerfluoroC8, but not the BDC8, stationary phase also exhibited significant retention of these analytes under conditions typical of an aqueous normal phase (ANP) mode (i.e. with mobile phases of >80% (v/v) ACN content), with the analytes exhibiting overall U-shape retention dependencies on the ACN content of the mobile phase. Further, these stationary phases showed differences in their selectivity behaviour with regard to the n-alkyl chain lengths of the different analytes. These observations could not be explained in terms of pK_a, log P, molecular mass or linear solvation energy concepts. However, density functional theory (DFT) simulations provided a possible explanation for the observed selectivity trends, namely differences in the molecular geometries and structural organisation of the immobilised ligands of these two stationary phases under different solvational conditions. For mobile phase conditions favouring the RP mode, these DFT simulations revealed that interactions between adjacent BDC8 ligands occur, leading to a stationary phase with a more hydrophobic surface. Moreover, under mobile phase conditions favouring retention of the analytes in an ANP mode, these interactions of the bidentate-anchored C8 ligands resulted in hindered analyte access to potential ANP binding sites on the BDC8 stationary phase surface. With the PerfluoroC8 stationary phase, the DFT simulations revealed strong repulsion of individual perfluoroC8 ligand chains, with the perfluoroC8 ligands of this stationary phase existing in a more open brush-like state (and with a less hydrophobic surface) compared to the BDC8 ligands. These DFT simulation results anticipated the chromatographic findings that the phenylalkanols and phenylalkylamines had reduced retention in the RP mode with the PerfluoroC8 stationary phase. Moreover, the more open ligand structure of the PerfluoroC8 stationary phase enabled greater accessibility of the analytes to water solvated binding sites on the stationary phase surface under mobile phase conditions favouring an ANP retention mode, leading to retention of the analytes, particularly the smaller phenylalkylamines, via hydrogen bonding and electrostatic effects.

In recent years, the commercialization of hybrid ion mobility-mass spectrometers and their integration in traditional LC-MS workflows provide new opportunities to extend the current boundaries of targeted and non-targeted analyses. When coupled to LC-MS, ion mobility spectrometry (IMS) provides a novel characterization parameter, the so-called averaged collision cross section (CCS, Ω), as well as improves method selectivity and sensitivity by the separation of isobaric and isomeric molecules and the isolation of the analytes of interest from background noise. In this work, we have explored the potential and advantages of this technology for carrying out the determination of phase II steroid metabolites (i.e. androgen and estrogen conjugates, including glucuronide and sulfate compounds; n = 25) in urine samples. These molecules have been selected based on their relevance in the fields of chemical food safety and doping control, as well as in metabolomics studies. The influence of urine matrix on the CCS of steroid metabolites was evaluated in order to give more confidence to current CCS databases and support its use as complementary information to retention time (Rt) and mass spectra for compound identification. Samples were only diluted 10-fold with aqueous formic acid (0.1%, v/v) prior analysis. Only an almost insignificant effect of adult bovine urine matrix on the CCS of certain steroid metabolites was observed in comparison with calve urine matrix, which is a less complex sample. In addition, high accuracy was achieved for CCS measurements carried out over four months (ΔCCS < 1.3% for 99.8% of CCS measurements; n = 1806). Interestingly, it has been observed that signal-to-noise (S/N) ratio could be improved at least 2 or 7-fold when IMS is combined with LC-MS. In addition to the separation of isomeric steroid pairs (i.e. etiocholanolone glucuronide and epiandrosterone glucuronide, as well as 19-noretiocholanolone glucuronide and 19-norandrosterone glucuronide), steroid-based ions were also separated in the IMS dimension from co-eluting matrix compounds that presented similar mass-to-charge ratio (m/z). Finally, based on CCS measurements and as a proof of concept, 17α-boldenone glucuronide has been identified as one of the main metabolites resulted from boldione administration to calves.

Small organic molecules are used as solution additives in electrospray ionisation mass spectrometry (ESI-MS) to increase the charge states of protein ions and improve the performance of intact protein analysis by tandem mass spectrometry. The properties of the additives that are responsible for their charge-enhancing effects (e.g. dipole moment, gas-phase basicity, Brønsted basicity, and surface tension) have been debated in the literature. We report a series of solution additives for ESI-MS based on cyclic alkyl carbonates and sulphites that have alkyl chains that are from two to ten methylene units long. The extent of charging of [Val [5]]-angiotensin II, cytochrome c, carbonic anhydrase II, and bovine serum albumin in ESI-MS using the additives was measured. For both the alkyl carbonate and sulphite additives with up to four methylene units, ion charging increased as the side chain lengths of the additives increased. At a critical alkyl chain length of four methylene units, protein ion charge states decreased as the chain length increased. The dipole moments, gas-phase basicity values, and Brønsted basicities (i.e. the pK_a of the conjugate acids) of the additives were obtained using electronic structure calculations, and the surface tensions were measured by pendant drop tensiometry. Because the dipole moments, gas-phase basicities, and pK_a values of the additives did not depend significantly on the alkyl chain lengths of the additives and the extent of charging depended strongly on the chain lengths, these data indicate that these three additive properties do not correlate with protein charging under these conditions. For the additives with alkyl chains at or above the critical length, the surface tension of the additives decreased as the length of the side chain decreased, which correlated well with the decrease in protein charging. These data are consistent with protein charging being limited by droplet surface tension below a threshold surface tension for these additives. For additives with relatively high surface tensions, protein ion charging increased as the amphiphilicity of the additives increased (and surface tension decreased) which is consistent with protein charging being limited by the emission of charge carriers from highly charged ESI generated droplets.

Non-targeted analysis is nowadays applied in many different domains of analytical chemistry such as metabolomics, environmental and food analysis. Conventional processing strategies for GC-MS data include baseline correction, feature detection, and retention time alignment before multivariate modeling. These techniques can be prone to errors and therefore time-consuming manual corrections are generally necessary. We introduce here a novel fully automated approach to non-targeted GC-MS data processing. This new approach avoids feature extraction and retention time alignment. Supervised machine learning on decomposed tensors of segmented chromatographic raw data signal is used to rank regions in the chromatograms contributing to differentiation between sample classes. The performance of this novel data analysis approach is demonstrated on three published datasets.

Botulinum neurotoxins (BoNTs) are classified at a highest degree of threat in biodefense, due largely to their high lethality. With the growing risk of biowarfare, the shortcomings of the gold standard test for these neurotoxins, the mouse bioassay, have underscored the need to develop alternative diagnostic testing strategies. This paper reports on the detection of inactivated Clostridium botulinum neurotoxin serotype A (BoNT-A) and serotype B (BoNT-B), the two most important markers of botulism infection, by using a sandwich immunoassay, gold nanoparticle labels, and surface-enhanced Raman scattering (SERS) within the context of two threat scenarios. The first scenario mimics part of the analysis needed in response to a “white powder” threat by measuring both neurotoxins in phosphate-buffered saline (PBS), a biocompatible solvent often used to recover markers dispersed in a powdered matrix. The second scenario detects the two neurotoxins in spiked human serum to assess the clinical potential of the platform. The overall goal is to develop a test applicable to both scenarios in terms of projections of required levels of detection. We demonstrate the ability to measure BoNT-A and BoNT-B in PBS at a limit of detection (LoD) of 700 pg/mL (5 pM) and 84 pg/mL (0.6 pM), respectively, and in human serum at 1200 pg/mL (8 pM) and 91 pg/mL (0.6 pM), respectively, with a time to result under 24 h. The steps required to transform this platform into an onsite biodefense screening tool that can simultaneously and rapidly detect (<1 h) these and other agents are briefly discussed.

Titanate nanosheets (single layer, typically 200 nm lateral size) deposited from aqueous colloidal solution onto electrode surfaces form lamellar hosts that bind redox active molecular redox probes. Here, hydrophobic redox systems such as anthraquinone, 1-amino-anthraquinone, deca-methylferrocene, 5,10,15,20-tetraphenyl-21H,23H-porphine manganese (III) chloride (TPPMnCl), and α-tocopherol are shown to bind directly from cyclopentanone solution (and from other types of organic solvents) into the titanate nanosheet film. For anthraquinone derivatives, stable voltammetric responses are observed in aqueous media consistent with 2-electron 2-proton reduction, however, independent of the pH of the outside solution phase environments. For decamethylferrocene a gradual decay of the voltammetric response is observed, but for TPPMnCl a more stable voltammetric signal is seen when immersed in chloride containing (NaCl) electrolyte. α-Tocopherol exhibits chemically irreversible oxidation and is detected with 1 mM–20 mM linear range and approximately 10⁻³ M concentration limit of detection. All redox processes exhibit an increase in current with increasing titanate film thickness and with increasing external electrolyte concentration. This and other observations suggest that important factors are analyte concentration and mobility within the titanate host, as well as ion exchange between titanate nanosheets and the outside electrolyte phase to maintain electroneutrality during voltammetric experiments. The lamellar titanate (with embedded tetrabutyl-ammonium cations) behaves like a hydrophobic host (for hydrophobic redox systems) similar to hydrophobic organic microphase systems. Potential for analytical applications is discussed.

Data management in universities is a challenging endeavor in particular due to the diverse infrastructure of devices and software in combination with limited budget. Nevertheless, in particular the analytical measurements and data sets need to be stored if possible digitally and in a well-organized manner. This manuscript describes how scientists can achieve a data management workflow focusing on data capture and storage by small adaptions to commonly used systems. The presented method includes data transfer options from ubiquitous devices like NMR instruments, GC (MS) or LC (MS), IR and Raman, or mass spectrometers to a central server and the visualization of the available data files in an electronic lab notebook (ELN). The given instruments were chosen according to the needs of synthetic chemists, in particular devices needed in organic, inorganic and polymer chemistry where single data files in the range of several megabytes per data set are produced. Altogether, three different data transfer systems were elaborated to allow a flexible handling of different devices running with different proprietary software: The first procedure allows data capture via the use of a mail server as data exchange point. With the second procedure, data are automatically mirrored from a local file folder to a central storage server where new files are monitored and processed. The third procedure was designed to transfer data with manual support to a central server which is supervised to register new information. All components that are necessary to install and use the herein elaborated functions are available as Open Source and the designed workflows are described step by step to facilitate the adaption of procedures in other universities accordingly if desired.

The interaction thermodynamics of the thrombin receptor agonistic peptide (TRAP-1), H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-OH, and a set of alanine scan substitution peptides, have been investigated with an n-octadecylacrylic polymer-bonded porous silica (Sil-ODA₁₈) and water-acetonitrile mobile phases at temperatures ranging from 5 to 80 °C in 5 °C increments. The retention of these peptides on the Sil-ODA₁₈ stationary phase decreased as the water content in the mobile phase was lowered from 80% (v/v) to ca. 45% (v/v) and reached a minimum value for each peptide at a specific water-acetonitrile composition. Further decreases in the water content of the mobile phase led to increased retention. The magnitude of the changes in enthalpy of interaction, $\text{Δ}{H}_{assoc}^0$, changes in entropy of interaction, $\text{Δ}{S}_{assoc}^0$, and changes in heat capacity, $\text{Δ}{C}_p^0$, were found to be dependent on the molecular properties of the mobile phase, the temperature, the structure/mobility of the stationary phase, and the conformation and solvation state of the peptides. With water-rich mobile phases, the retention behaviour of the TRAP analogues was dominated by enthalpic processes, consistent with the participation of strong hydrogen bonding effects, but became dominated by entropic effects with acetonitrile-rich mobile phases as the temperature was increased. These changes in the retention behaviour of these TRAP peptides are consistent with the generation of water or acetonitrile clusters in the mobile phase depending on the volume fractions of the organic solvent as the Sil-ODA₁₈ stationary phase transitions from its crystalline to its isotropic state.