TY - JOUR A1 - Ickert, Stefanie A1 - Beck, S. A1 - Linscheid, M. A1 - Riedel, Jens T1 - VUV Photodissociation Induced by a Deuterium Lamp in an Ion Trap N2 - Tandem mass spectrometry represents an important analytical tool to unravel molecular structures and to study the gas-phase behavior of organic molecules. Besides commonly used methods like collision-induced dissociation and electron capture or transfer dissociation, new ultraviolet light–based techniques have the potential to synergistically add to the activation methods. Here, we present a new simple, yet robust, experimental design for polychromatic activation of trapped ions using the 115–160 nm output of a commercially available deuterium lamp. The resulting continuous dissociative excitation with photons of a wide energy range from 7.7 to 10.8 eV is studied for a comprehensive set of analyte classes in both positive and negative ion modes. While being simple, affordable, compact, and of low maintenance, the new setup initiates fragmentation of most precursor ions via their known dissociation pathways. Additionally, some new fragmentation patterns were discovered. Especially, electron loss and electron capture reactions with subsequent fragmentations were observed. For oligonucleotides, peptides, carbohydrates, and organic dyes, in comparison to collision-induced dissociation, a significantly wider fragment distribution was obtained, resulting in an information increase. Since the individual photons carry enough energy to post-ionize the nascent fragments, a permanent vacuum ultraviolet light exposure inside the ion trap potentially goes along with a general increase in detection capability. KW - Fragmentation activation KW - Vacuum ultraviolet (VUV) light KW - Mass spectrometry KW - Tandem MS PY - 2019 DO - https://doi.org/10.1007/s13361-019-02282-8 SN - 1044-0305 VL - 30 IS - 10 SP - 2114 EP - 2122 PB - Springer Nature CY - Heidelberg AN - OPUS4-48756 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bauer, M. A1 - Remmler, D. A1 - Dallmann, A. A1 - Jakubowski, Norbert A1 - Börner, H. G. A1 - Panne, Ulrich A1 - Limberg, C. T1 - Specific Decoration of a Discrete Bismuth Oxido Cluster by Selected Peptides towards the Design of Metal Tags N2 - Metal tags find application in a multitude of biomedical systems and the combination with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) offers an opportunity for multiplexing. To lay the foundation for an increase of the signal intensities in such processes, we herein present a general approach for efficient functionalization of a well-defined metal oxido cluster [Bi6O4(OH)(4)(SO3CF3)(6)(CH3CN)(6)].2 CH3CN (1), which can be realized by selecting 7mer peptide sequences via combinatorial means from large one-bead one-compound peptide libraries. Selective cluster-binding peptide sequences (CBS) for 1 were discriminated from non-binders by treatment with H2S gas to form the reduction product Bi2S3, clearly visible to the naked eye. Interactions were further confirmed by NMR experiments. Extension of a binding peptide with a maleimide linker (Mal) introduces the possibility to covalently attach thiol-bearing moieties such as biological probes and for their analysis the presence of the cluster instead of mononuclear entities should lead to an increase of signal intensities in LA-ICP-MS measurements. To prove this, CBS-Mal was covalently bound onto thiol-presenting glass substrates, which then captured 1 effectively, so that LA-ICP-MS measurements demonstrated drastic signal amplification compared to single lanthanide tags. KW - Peptide library KW - Mass spectrometry KW - Laser ablation KW - Cluster KW - Bioconjugation PY - 2019 DO - https://doi.org/10.1002/chem.201805234 SN - 0947-6539 VL - 25 IS - 3 SP - 759 EP - 763 PB - John Wiley & Sons, Inc. AN - OPUS4-47324 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Jaeger, Carsten A1 - Lisec, Jan T1 - Rapid characterization of ionization products for chemistry-aware compound annotation in nontargeted small molecule mass spectrometry N2 - Nontargeted high-resolution mass spectrometry (HRMS) is widely used for small molecule screening in biotic or abiotic samples. However, HRMS approaches like metabolomics or environmental nontarget screening currently still lack confidence in chemical annotation, i.e. computational structure assignment to all measured mass signals. As a crucial step within the annotation pipeline, molecular weight inference (MWI) deduces a compound’s intact mass from diagnostic mass differences between MS1 peaks, allowing precise database queries in subsequent steps. As the common practice of considering all possible ionization products such as adducts, multimers, multiple charges etc. in MWI suffers from high false positive rates, we aimed at selecting candidate ionization products in a chemically sensitive way. Generally, electrospray ionization produces different types of adducts depending on chromatographic system and sample matrix, necessitating application-specific optimization for optimum MWI performance. To avoid, however, the tedious and potentially biased manual data curation connected to optimization, we established an R-based workflow for automating this task. The workflow consists of two parts. Part 1 creates an MS1 spectral library by performing peak detection, spectral deconvolution and target peak assignment based on density estimation. Part 2 analyzes ion relationships within the library and returns a list of detected ionization products ranked by their frequency. We applied the workflow to a commercial 634-compound library that was acquired for two chromatographic methods (reverse phase, RP; hydrophilic liquid interaction chromatographic, HILIC) and the two ESI modes (positive, negative). As expected, different frequency distributions of ionization products were found for the two chromatographies. Interestingly, however, some of the differences were expected in terms of solvent chemistries (e.g. [M+NH4]+ in ammonium formate-buffered HILIC) while others indicated more complex ion competition (e.g. abundant [M+K]+, [M+2K-H]+ in HILIC). This demonstrated the relevance of this empirical approach. We further show that MWI accuracy clearly benefitted from derived optimized adduct lists – by adding filters or weighting terms – and present FDR calculations supporting this observation. We conclude that chemistry-aware compound annotation based on the combination of high-throughput library acquisition and statistical analysis holds significant potential for further improvements in nontargeted small molecule HRMS. T2 - ANAKON 2019 CY - Münster, Germany DA - 25.03.2019 KW - Compound annotation KW - Mass spectrometry KW - Electrospray ionization KW - Nontarget analysis KW - Accurate mass PY - 2019 AN - OPUS4-48332 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Jaeger, Carsten T1 - Improving Small Molecule Annotation In Nontargeted Soft Ionization GC/LC High Resolution Mass Spectrometry N2 - High-resolution mass spectrometry, either combined with gas or liquid chromatography (GC/LC-HR-MS), is currently the most powerful analytical option for broad nontargeted small molecule analysis. To transform HR-MS raw data from metabolomics or environmental studies into chemically meaningful data, several computational steps are needed, including peak detection, deconvolution of these peaks into compounds and putative identification of compounds using databases. Each of these steps can cause problems and still requires methodological advancements. Computational compound annotation as one of the steps, however, has proven particularly challenging, mainly due to the chemical diversity of organic analytes. In addition, different annotation approaches are needed for the different platforms used in HR-MS screening. We recently introduced InterpretMSSpectrum as an annotation workflow for GC-HR-MS using atmospheric pressure chemical ionization (APCI). InterpretMSSpectrum locates molecular ion, fragment and adduct peaks, calculates their most likely sum formula combination and graphically summarizes results as an annotated mass spectrum. As a complementary approach for LC-HR-MS, we presented findMAIN, which scores MS1 spectra based on explained intensity, mass accuracy and isotope charge agreement of adducts and related electrospray ionization (ESI) products to determine the neutral mass of unknown compounds. Both approaches were validated against large spectral libraries containing more than 600 compounds, for which correct annotation was achieved in over 80% of the cases. Based on the experiences from this validation, we here compare soft-ionization GC/LC-HR-MS regarding “annotatability” of unknown compounds from a computational perspective. As a main advantage for GC-HR-MS, the relatively uniform ionization behavior of commonly used trimethylsilyl (TMS) derivatives observed under APCI allowed differentiation of molecular ion peaks from in-source fragments based on relatively compact set of rules. By contrast, neutral mass inference in ESI required a more complex evaluation scheme, due to the higher diversity of ionization products observable in ESI. We demonstrate such differences by practical examples of both software packages applied to metabolomics studies and discuss the challenges connected to transferring the approaches to environmental screening. T2 - ACS Fall Meeting 2019 CY - San Diego, CA, USA DA - 25.09.2019 KW - Compound annotation KW - Mass spectrometry KW - Electrospray ionization KW - Nontarget analysis KW - Accurate mass PY - 2019 AN - OPUS4-49200 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -