Pub Date : 2026-01-01Epub Date: 2025-11-11DOI: 10.1016/j.ijms.2025.117551
Hadja Fatima Tbahriti , Ali Boukadoum , Esraa Mohamed Ahmed Mohamed Eljamil
Neurodegenerative disorders are highly prevalent diseases, representing a significant health care burden for millions of individuals worldwide, with scarce diagnostic and therapeutic capabilities. Conventional mass spectrometry methods for assessing biomarkers, although powerful, suffer from limited sensitivity, specificity and interpretability in complex biological matrices. This work introduces a new methodology that combines generative machine learning models and physics-based constraints for the discovery of biomarkers in neurodegenerative diseases. Next, we take advantage of the underlying mass spectrometry physics, including principles like mass conservation, isotope patterns and fragmentation rules, to impose on our generative models to generate biologically interpretable spectral representations. The framework shows better results compared with the traditional methods (AUC = 0.93 on multiple datasets across neurodegenerative diseases, sensitivity and specificity of 89.3 % and 92.1 %, respectively). Our approach, which integrates physics-informed constraints within a VAE-GAN framework, holds the potential to improve the precision of biomarker detection while providing interpretable insights into the biological mechanisms driving neurodegeneration. This present work introduces a revolutionary new paradigm for computational mass spectrometry, which acts as a bridge between data-driven discovery and mechanistic explanation, with exciting possibilities for early diagnosis and therapeutic target intervention in neurodegenerative disease.
{"title":"Generative mass spectrometry via physics-informed machine learning: A framework for biomarker discovery in neurodegenerative diseases","authors":"Hadja Fatima Tbahriti , Ali Boukadoum , Esraa Mohamed Ahmed Mohamed Eljamil","doi":"10.1016/j.ijms.2025.117551","DOIUrl":"10.1016/j.ijms.2025.117551","url":null,"abstract":"<div><div>Neurodegenerative disorders are highly prevalent diseases, representing a significant health care burden for millions of individuals worldwide, with scarce diagnostic and therapeutic capabilities. Conventional mass spectrometry methods for assessing biomarkers, although powerful, suffer from limited sensitivity, specificity and interpretability in complex biological matrices. This work introduces a new methodology that combines generative machine learning models and physics-based constraints for the discovery of biomarkers in neurodegenerative diseases. Next, we take advantage of the underlying mass spectrometry physics, including principles like mass conservation, isotope patterns and fragmentation rules, to impose on our generative models to generate biologically interpretable spectral representations. The framework shows better results compared with the traditional methods (AUC = 0.93 on multiple datasets across neurodegenerative diseases, sensitivity and specificity of 89.3 % and 92.1 %, respectively). Our approach, which integrates physics-informed constraints within a VAE-GAN framework, holds the potential to improve the precision of biomarker detection while providing interpretable insights into the biological mechanisms driving neurodegeneration. This present work introduces a revolutionary new paradigm for computational mass spectrometry, which acts as a bridge between data-driven discovery and mechanistic explanation, with exciting possibilities for early diagnosis and therapeutic target intervention in neurodegenerative disease.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117551"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-05DOI: 10.1016/j.ijms.2025.117548
Matjaž Finšgar, Katja Andrina Varda
This study focuses on the surface and subsurface characterization of a pharmaceutical tablet containing sodium metamizolate (NaMET), with an emphasis on mass spectrometry using time-of-flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS enabled the identification of NaMET-specific fragment ions, which served as signals for the determination of the spatial distribution of this active pharmaceutical ingredient (API) within the tablet matrix. A ToF-SIMS fragmentation mechanism for NaMET was proposed based on the ToF-SIMS spectra analysis measured on a NaMET reference standard. 3D ToF-SIMS imaging showed heterogeneous localization of the API across a 5 μm depth. Complementary techniques, including 3D profilometry and atomic force microscopy (AFM), provided surface roughness and morphological data, while X-ray photoelectron spectroscopy (XPS) confirmed the elemental composition and chemical states. Depth profiling by XPS further supported the non-uniform distribution of NaMET.
{"title":"Surface analysis of sodium metamizolate as an active pharmaceutical ingredient in solid form","authors":"Matjaž Finšgar, Katja Andrina Varda","doi":"10.1016/j.ijms.2025.117548","DOIUrl":"10.1016/j.ijms.2025.117548","url":null,"abstract":"<div><div>This study focuses on the surface and subsurface characterization of a pharmaceutical tablet containing sodium metamizolate (NaMET), with an emphasis on mass spectrometry using time-of-flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS enabled the identification of NaMET-specific fragment ions, which served as signals for the determination of the spatial distribution of this active pharmaceutical ingredient (API) within the tablet matrix. A ToF-SIMS fragmentation mechanism for NaMET was proposed based on the ToF-SIMS spectra analysis measured on a NaMET reference standard. 3D ToF-SIMS imaging showed heterogeneous localization of the API across a 5 μm depth. Complementary techniques, including 3D profilometry and atomic force microscopy (AFM), provided surface roughness and morphological data, while X-ray photoelectron spectroscopy (XPS) confirmed the elemental composition and chemical states. Depth profiling by XPS further supported the non-uniform distribution of NaMET.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117548"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-30DOI: 10.1016/j.ijms.2025.117516
I-Chung Lu
Matrix-assisted laser desorption/ionization (MALDI) is a vital analytical tool, but the fundamental ionization mechanism has long been debated. This perspective summarizes over a decade of research to introduce a comprehensive thermal framework, culminating in the quantitative thermally induced proton transfer (TIPT) model for MALDI. Validated by numerous experiments without fitting parameters, we identify that laser-induced temperature is the dominant factor in the primary ionization of protonated ions. The principle was subsequently applied to resolve the longstanding challenges of carbohydrate analysis. To overcome the characteristically low sensitivity of carbohydrates, the rapidly freeze-drying droplet (RFDD) sample preparation method was developed by preserving homogeneously distributed, preformed sodium adducts. RFDD increases ion intensity by over two orders of magnitude, eliminates the "sweet spot" effect, and enables reliable quantitative analysis. This journey from fundamental mechanistic inquiry to a practical, innovative technology powerfully illustrates how basic science drives analytical advancements.
{"title":"A thermal perspective on MALDI ionization: A long journey from fundamental mechanisms to a practical solution for carbohydrate analysis","authors":"I-Chung Lu","doi":"10.1016/j.ijms.2025.117516","DOIUrl":"10.1016/j.ijms.2025.117516","url":null,"abstract":"<div><div>Matrix-assisted laser desorption/ionization (MALDI) is a vital analytical tool, but the fundamental ionization mechanism has long been debated. This perspective summarizes over a decade of research to introduce a comprehensive thermal framework, culminating in the quantitative thermally induced proton transfer (TIPT) model for MALDI. Validated by numerous experiments without fitting parameters, we identify that laser-induced temperature is the dominant factor in the primary ionization of protonated ions. The principle was subsequently applied to resolve the longstanding challenges of carbohydrate analysis. To overcome the characteristically low sensitivity of carbohydrates, the rapidly freeze-drying droplet (RFDD) sample preparation method was developed by preserving homogeneously distributed, preformed sodium adducts. RFDD increases ion intensity by over two orders of magnitude, eliminates the \"sweet spot\" effect, and enables reliable quantitative analysis. This journey from fundamental mechanistic inquiry to a practical, innovative technology powerfully illustrates how basic science drives analytical advancements.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117516"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-12DOI: 10.1016/j.ijms.2025.117509
Soumitra Das, Pramod Sharma, Chiranjib Majumder
Photoionization study of PCl3 clusters has been carried out using time-of-flight mass spectrometry at selected wavelengths of UV (266, 355 nm) and Visible (532 nm) region employing nanosecond laser pulses of intensity ∼109 W/cm2. At these three laser wavelengths, dissociated fragments such as P+, Cl+, PCl+ and PCl2+ are observed in the mass spectra. Formation of different fragments has been explained based on the multiphoton excitation at the respective wavelengths. Moreover, PCl4+ ions are observed in 266 and 355 nm ionization of PCl3 clusters. Generation of PCl4+ is explained based on ion-molecule reaction within the ionized cluster. Using density functional theory (DFT), structure, ionization energy and absorption spectra of PCl3 monomer and clusters have been calculated which helps to rationalize the experimental observation. Along with singly charged fragment ions, multiply charged atomic ions up to P5+ (I.E: 65.1 eV) and Cl4+ (I.E: 53.5 eV) are observed at 532 nm. Generation of multiply charged ions at such low laser intensity indicates efficient ionization of PCl3 clusters. Formation of higher charge states can be explained based on “multiphoton ionization ignited-inverse bremsstrahlung heating–electron ionization”. Detailed study reveals that laser intensity, cluster size and ionization energy of the cluster constituents play an important role in governing the ionization dynamics under gigawatt laser intensity conditions. Thus, PCl3 clusters exhibit diverse photochemical process as a function of laser wavelength at ∼109 W/cm2.
{"title":"Photoionization of phosphorous trichloride clusters at gigawatt intense laser field","authors":"Soumitra Das, Pramod Sharma, Chiranjib Majumder","doi":"10.1016/j.ijms.2025.117509","DOIUrl":"10.1016/j.ijms.2025.117509","url":null,"abstract":"<div><div>Photoionization study of PCl<sub>3</sub> clusters has been carried out using time-of-flight mass spectrometry at selected wavelengths of UV (266, 355 nm) and Visible (532 nm) region employing nanosecond laser pulses of intensity ∼10<sup>9</sup> W/cm<sup>2</sup>. At these three laser wavelengths, dissociated fragments such as P<sup>+</sup>, Cl<sup>+</sup>, PCl<sup>+</sup> and PCl<sub>2</sub><sup>+</sup> are observed in the mass spectra. Formation of different fragments has been explained based on the multiphoton excitation at the respective wavelengths. Moreover, PCl<sub>4</sub><sup>+</sup> ions are observed in 266 and 355 nm ionization of PCl<sub>3</sub> clusters. Generation of PCl<sub>4</sub><sup>+</sup> is explained based on ion-molecule reaction within the ionized cluster. Using density functional theory (DFT), structure, ionization energy and absorption spectra of PCl<sub>3</sub> monomer and clusters have been calculated which helps to rationalize the experimental observation. Along with singly charged fragment ions, multiply charged atomic ions up to P<sup>5+</sup> (I.E: 65.1 eV) and Cl<sup>4+</sup> (I.E: 53.5 eV) are observed at 532 nm. Generation of multiply charged ions at such low laser intensity indicates efficient ionization of PCl<sub>3</sub> clusters. Formation of higher charge states can be explained based on “multiphoton ionization ignited-inverse bremsstrahlung heating–electron ionization”. Detailed study reveals that laser intensity, cluster size and ionization energy of the cluster constituents play an important role in governing the ionization dynamics under gigawatt laser intensity conditions. Thus, PCl<sub>3</sub> clusters exhibit diverse photochemical process as a function of laser wavelength at ∼10<sup>9</sup> W/cm<sup>2</sup>.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117509"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-06DOI: 10.1016/j.ijms.2025.117527
Shraavani Konatam, Dijendra Nath Roy
The rising prevalence of biofilm-related infections and foodborne diseases, particularly those caused by Staphylococcus aureus, presents significant challenges to conventional treatment strategies due to the increasing phenomenon of antibiotic resistance caused by biofilm. In response, this study employed GC-MS analysis of the methanolic and n-hexane extracts of Terminalia arjuna bark, a traditional medicinal plant, and identified a diverse array of bioactive compounds. All 79 compounds identified from GC-MS data were examined to determine the best binding score with SrtA and SarA, two key proteins involved in the development of biofilms and the pathogenicity of Staphylococcus aureus. Among 79 compounds, D-Allose, a monosaccharide, demonstrated the best binding affinity with SrtA (−6.304 kcal/mol) by involving five hydrogen bonds and SarA (−5.101 kcal/mol) by involving three hydrogen bonds, compared to other compounds among 158 interactions. Molecular dynamics and simulations were performed for 100 ns to analyze the interaction parameters with SrtA and SarA. Corresponding MM-GBSA binding energy values were −33.66 kcal/mol (D-Allose with SrtA), −18.09 kcal/mol (D-Allose with SarA). The fact that D-Allose has zero violations of Lipinski's Rule of Five further exemplifies its suitability as a medication candidate. These interactions suggest that D-Allose may interfere with bacterial adhesion, quorum sensing, and the synthesis of the biofilm matrix by interacting with SrtA and SarA. To the best of our knowledge, this is the first study to elucidate the potential mechanism by which D-Allose exerts its antibiofilm activity. Future research on in vitro and in vivo studies should focus on experimental validation to establish D-Allose as a promising monosaccharide candidate for combating biofilm-related antibiotic-resistant Staphylococcus aureus infections.
{"title":"GC-MS unveils monosaccharide D-Allose in Terminalia arjuna bark extract acting against biofilm regulatory proteins (SrtA and SarA) of Staphylococcus aureus: A drug discovery approach","authors":"Shraavani Konatam, Dijendra Nath Roy","doi":"10.1016/j.ijms.2025.117527","DOIUrl":"10.1016/j.ijms.2025.117527","url":null,"abstract":"<div><div>The rising prevalence of biofilm-related infections and foodborne diseases, particularly those caused by <em>Staphylococcus aureus</em>, presents significant challenges to conventional treatment strategies due to the increasing phenomenon of antibiotic resistance caused by biofilm. In response, this study employed GC-MS analysis of the methanolic and n-hexane extracts of <em>Terminalia arjuna</em> bark, a traditional medicinal plant, and identified a diverse array of bioactive compounds. All 79 compounds identified from GC-MS data were examined to determine the best binding score with SrtA and SarA, two key proteins involved in the development of biofilms and the pathogenicity of <em>Staphylococcus aureus.</em> Among 79 compounds, D-Allose, a monosaccharide, demonstrated the best binding affinity with SrtA (−6.304 kcal/mol) by involving five hydrogen bonds and SarA (−5.101 kcal/mol) by involving three hydrogen bonds, compared to other compounds among 158 interactions. Molecular dynamics and simulations were performed for 100 ns to analyze the interaction parameters with SrtA and SarA. Corresponding MM-GBSA binding energy values were −33.66 kcal/mol (D-Allose with SrtA), −18.09 kcal/mol (D-Allose with SarA). The fact that D-Allose has zero violations of Lipinski's Rule of Five further exemplifies its suitability as a medication candidate. These interactions suggest that D-Allose may interfere with bacterial adhesion, quorum sensing, and the synthesis of the biofilm matrix by interacting with SrtA and SarA. To the best of our knowledge, this is the first study to elucidate the potential mechanism by which D-Allose exerts its antibiofilm activity. Future research on in vitro and <em>in vivo</em> studies should focus on experimental validation to establish D-Allose as a promising monosaccharide candidate for combating biofilm-related antibiotic-resistant <em>Staphylococcus aureus</em> infections.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117527"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-16DOI: 10.1016/j.ijms.2025.117510
Kerstin Strupat, Frederik Busse-Patel, Ralf Hartmer
Development and manufacturing of mRNA vaccines require frequent quality control measures to ensure product safety and efficacy. Mass Spectrometry in combination with Liquid Chromatography (LC-MS) is known as a powerful tool for sequence confirmation and assessment of post-transcriptional modifications. LC-MS methods, while accurate, suffer from long acquisition times, making them typically impractical for high-throughput applications.
This study introduces a novel approach for RNA oligonucleotide sequence confirmation using UV-MALDI at atmospheric pressure (AP-MALDI) coupled with high-resolution accurate mass (HRAM) Orbitrap™ mass analyzer technology. By using an Orbitrap detector, we achieve a mass accuracy below 2 ppm for the digestion products of a RNA digest, suitable for verifying oligonucleotide sequences from complex mixtures without prior separation. We employ RNase T1 owing its G-specific cleavage, an ammonium-activated cation exchange resin for purification, followed by AP-UV-MALDI MS analysis. The method is validated with a synthetic 119mer RNA oligonucleotide, confirming sequence identity through MS/MS in both positive and negative ion modes. The approach is further applied to in silico analysis of mRNA sequences from vaccine variants, showcasing its potential for high-throughput, rapid sequence confirmation, and variant differentiation in RNA, particularly relevant for mRNA vaccine development and quality control in biopharmaceutical manufacturing.
{"title":"Concept for high-throughput mRNA sequence confirmation by atmospheric pressure MALDI technique applied to RNA digestion products","authors":"Kerstin Strupat, Frederik Busse-Patel, Ralf Hartmer","doi":"10.1016/j.ijms.2025.117510","DOIUrl":"10.1016/j.ijms.2025.117510","url":null,"abstract":"<div><div>Development and manufacturing of mRNA vaccines require frequent quality control measures to ensure product safety and efficacy. Mass Spectrometry in combination with Liquid Chromatography (LC-MS) is known as a powerful tool for sequence confirmation and assessment of post-transcriptional modifications. LC-MS methods, while accurate, suffer from long acquisition times, making them typically impractical for high-throughput applications.</div><div>This study introduces a novel approach for RNA oligonucleotide sequence confirmation using UV-MALDI at atmospheric pressure (AP-MALDI) coupled with high-resolution accurate mass (HRAM) Orbitrap™ mass analyzer technology. By using an Orbitrap detector, we achieve a mass accuracy below 2 ppm for the digestion products of a RNA digest, suitable for verifying oligonucleotide sequences from complex mixtures without prior separation. We employ RNase T1 owing its G-specific cleavage, an ammonium-activated cation exchange resin for purification, followed by AP-UV-MALDI MS analysis. The method is validated with a synthetic 119mer RNA oligonucleotide, confirming sequence identity through MS/MS in both positive and negative ion modes. The approach is further applied to <em>in silico</em> analysis of mRNA sequences from vaccine variants, showcasing its potential for high-throughput, rapid sequence confirmation, and variant differentiation in RNA, particularly relevant for mRNA vaccine development and quality control in biopharmaceutical manufacturing.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117510"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-03DOI: 10.1016/j.ijms.2025.117525
P.B. Armentrout , Bastiaan Poetsma , David H. Loertscher , Satish Kumar , Joost M. Bakker
Products resulting from the sequential activation of four and five methane molecules by atomic tantalum cations were characterized by gas-phase infrared multiple photon dissociation spectroscopy and density functional theory (DFT) calculations. Tantalum cations were generated using a laser ablation source and reacted with methane in a linear radiofrequency ion trap before mass analysis and spectroscopic interrogation in a Fourier transform ion cyclotron resonance mass spectrometer coupled to the free-electron laser for intracavity experiments (FELICE) beamline. Product ions were irradiated using infrared light over the 300−2000 cm−1 spectral range. Comparisons between the experimental and DFT-calculated spectra enabled structural determination of the products formed. The observed products are (CH3)2TaC2H2+ and (CH3)3Ta(C2H3)+. Formation of these products provides evidence for efficient C−H bond activation and subsequent C−C coupling on the atomic tantalum cation.
通过气相红外多光子解离光谱和密度泛函理论（DFT）计算，对原子钽离子连续激活4和5个甲烷分子的产物进行了表征。利用激光烧蚀源生成钽离子，在线性射频离子阱中与甲烷反应，然后在傅里叶变换离子回旋共振质谱仪耦合到腔内实验自由电子激光器（FELICE）光束线进行质量分析和光谱询问。产品离子在300 - 2000 cm - 1光谱范围内用红外光照射。实验光谱和dft计算光谱之间的比较使形成的产物的结构确定成为可能。产物为（CH3）2TaC2H2+和（CH3）3Ta(C2H3)+。这些产物的形成为有效的C - H键激活和随后在原子钽阳离子上的C - C偶联提供了证据。
{"title":"Structures of species formed by sequential methane activation by Ta+: Infrared multiple photon dissociation spectroscopy and ab Initio calculations","authors":"P.B. Armentrout , Bastiaan Poetsma , David H. Loertscher , Satish Kumar , Joost M. Bakker","doi":"10.1016/j.ijms.2025.117525","DOIUrl":"10.1016/j.ijms.2025.117525","url":null,"abstract":"<div><div>Products resulting from the sequential activation of four and five methane molecules by atomic tantalum cations were characterized by gas-phase infrared multiple photon dissociation spectroscopy and density functional theory (DFT) calculations. Tantalum cations were generated using a laser ablation source and reacted with methane in a linear radiofrequency ion trap before mass analysis and spectroscopic interrogation in a Fourier transform ion cyclotron resonance mass spectrometer coupled to the free-electron laser for intracavity experiments (FELICE) beamline. Product ions were irradiated using infrared light over the 300−2000 cm<sup>−1</sup> spectral range. Comparisons between the experimental and DFT-calculated spectra enabled structural determination of the products formed. The observed products are (CH<sub>3</sub>)<sub>2</sub>TaC<sub>2</sub>H<sub>2</sub><sup>+</sup> and (CH<sub>3</sub>)<sub>3</sub>Ta(C<sub>2</sub>H<sub>3</sub>)<sup>+</sup>. Formation of these products provides evidence for efficient C−H bond activation and subsequent C−C coupling on the atomic tantalum cation.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117525"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-25DOI: 10.1016/j.ijms.2025.117514
G. Asher Newsome , Katja S. Diaz-Granados , Karen Sam , Joshua D. Caldwell , Erin R. Birdsall
Real-time sampling systems are assembled for analysis of pyrolyzed material using in-line ionization and high resolution mass spectrometry. Two commercial models of Pyroprobe pyrolyzer with either a wand-mounted coil or a drop-in sample chamber are reconfigured from the standard gas chromatograph interface. Either a flow cell containing a platinum coil or a drop-in pyrolysis chamber is connected to a heated transfer line that conducts pyrolysates directly to a photoionization or dielectric barrier discharge source. The ion source is mounted to the front of an Orbitrap system, drawing analyte through from the pyrolyzer using instrument vacuum and/or supplementary pumping. The mass spectrometer scans in rapidly-alternating polarity so that positive and negative mode analyses are acquired in a single run. Pyrolyzed samples of tens of micrograms of polymeric materials yielded robust and resolved signal, especially from halogenated ions in negative mode that otherwise did not produce enough electron impact ionization signal for identification. The photoionization source in particular was easily purged of lingering pyrolysate by temporarily increasing the supplemental flow rate, rapidly returning signal to baseline levels after an analytical run. Elimination of carryover allowed replicate analyses to be collected at a rate of every 2 min without an autosampler. Slow-ramp thermal extraction analyses was performed on the same system as flash pyrolysis without any change in hardware.
{"title":"Pyrolysis and thermal extraction of polymeric materials with suction-driven, real-time ionization sources and rapid polarity switching, high resolution mass spectrometry","authors":"G. Asher Newsome , Katja S. Diaz-Granados , Karen Sam , Joshua D. Caldwell , Erin R. Birdsall","doi":"10.1016/j.ijms.2025.117514","DOIUrl":"10.1016/j.ijms.2025.117514","url":null,"abstract":"<div><div>Real-time sampling systems are assembled for analysis of pyrolyzed material using in-line ionization and high resolution mass spectrometry. Two commercial models of Pyroprobe pyrolyzer with either a wand-mounted coil or a drop-in sample chamber are reconfigured from the standard gas chromatograph interface. Either a flow cell containing a platinum coil or a drop-in pyrolysis chamber is connected to a heated transfer line that conducts pyrolysates directly to a photoionization or dielectric barrier discharge source. The ion source is mounted to the front of an Orbitrap system, drawing analyte through from the pyrolyzer using instrument vacuum and/or supplementary pumping. The mass spectrometer scans in rapidly-alternating polarity so that positive and negative mode analyses are acquired in a single run. Pyrolyzed samples of tens of micrograms of polymeric materials yielded robust and resolved signal, especially from halogenated ions in negative mode that otherwise did not produce enough electron impact ionization signal for identification. The photoionization source in particular was easily purged of lingering pyrolysate by temporarily increasing the supplemental flow rate, rapidly returning signal to baseline levels after an analytical run. Elimination of carryover allowed replicate analyses to be collected at a rate of every 2 min without an autosampler. Slow-ramp thermal extraction analyses was performed on the same system as flash pyrolysis without any change in hardware.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117514"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-21DOI: 10.1016/j.ijms.2025.117513
Chenqin Cao , Sophie Liuu , Ekaterina Darii , Amandine Hueber , Yves Gimbert , Annelaure Damont , Olivier Firmesse , François Fenaille , Jean-Claude Tabet
Under positive electrospray desorption/ionization mass spectrometry (ESI-MS) conditions, a bacterial cyclodepsipeptide toxin, cereulide [(D)Ala-(L)OVal-(L)Val-(D)OLeu]3, is mainly desorbed as ammonium adduct and alkali-cationized species. In addition to the naturally occurring alkali cation (Li+/Na+/K+), Rb+ can be attached to the molecule after addition of its chlorine salt (RbCl) solution. Under non-resonant collision-induced dissociations (non-resonant CID) using a quadrupole time-of-flight (Qq/TOF) instrument, bare alkali cations were recently detected in non-resonant CID spectra. Investigation using energy-resolved mass spectrometry (ERMS) of cationized cereulide revealed coexistence of charge-solvated (CS) and protonated salt (PS) tautomers. Infusion of cereulide solution containing RbCl salt into the ion source led to the unexpected detection of 85Rb+ and 87Rb+ within their natural abundances when Rb-free species ([M + NH4]+, [M+Na]+ or [M+K]+) were selected for subsequent fragmentation. To elucidate the origin of these unexpected cations, ERMS of the various ionized cereulide species was carried out using an Orbitrap-based instrument. Curiously, in addition to the unexpected Rb+ isotopique cations, Rb2Cl+ isotopologues were abundantly detected in non-resonant CID spectra of [M + NH4]+, [M+Na]+, and [M+K]+, but not of [M+85Rb]+. Additional calculations and ERMS logarithmic plots made it possible to rule out a possible endogenous origin of the Rb2Cl+ and Rb+ isotopologues. They are produced by ion/molecule reactions in the higher-energy collisional dissociation (HCD) cell between ionized cereulide (and b(12-n) ions), relaxed by the buffer gas, and neutral RbCl isotopologue salts present in gas phase. The latter are likely generated either during preliminary studies of RbnCl(n-1)+ cluster dissociation in smaller cluster ions and neutral RbCl loss, or from the HCD cell surface by collisions with the buffer gas. Consequently, Rb2Cl+ isotopologues are not precursors of 85Rb+ plus 87Rb+.
{"title":"Revealing the unexpected: formal charge exchanges in collisional activation of cereulide ionized molecular species","authors":"Chenqin Cao , Sophie Liuu , Ekaterina Darii , Amandine Hueber , Yves Gimbert , Annelaure Damont , Olivier Firmesse , François Fenaille , Jean-Claude Tabet","doi":"10.1016/j.ijms.2025.117513","DOIUrl":"10.1016/j.ijms.2025.117513","url":null,"abstract":"<div><div>Under positive electrospray desorption/ionization mass spectrometry (ESI-MS) conditions, a bacterial cyclodepsipeptide toxin, cereulide [<sup>(D)</sup>Ala-<sup>(L)O</sup>Val-<sup>(L)</sup>Val-<sup>(D)O</sup>Leu]<sub>3</sub>, is mainly desorbed as ammonium adduct and alkali-cationized species. In addition to the naturally occurring alkali cation (Li<sup>+</sup>/Na<sup>+</sup>/K<sup>+</sup>), Rb<sup>+</sup> can be attached to the molecule after addition of its chlorine salt (RbCl) solution. Under non-resonant collision-induced dissociations (non-resonant CID) using a quadrupole time-of-flight (Qq/TOF) instrument, bare alkali cations were recently detected in non-resonant CID spectra. Investigation using energy-resolved mass spectrometry (ERMS) of cationized cereulide revealed coexistence of <strong><em>charge-solvated (CS)</em></strong> and <strong><em>protonated salt (PS)</em></strong> tautomers. Infusion of cereulide solution containing RbCl salt into the ion source led to the unexpected detection of <sup>85</sup>Rb<sup>+</sup> and <sup>87</sup>Rb<sup>+</sup> within their natural abundances when Rb-free species ([M + NH<sub>4</sub>]<sup>+</sup>, [M+Na]<sup>+</sup> or [M+K]<sup>+</sup>) were selected for subsequent fragmentation. To elucidate the origin of these unexpected cations, ERMS of the various ionized cereulide species was carried out using an Orbitrap-based instrument. Curiously, in addition to the unexpected Rb<sup>+</sup> isotopique cations, Rb<sub>2</sub>Cl<sup>+</sup> isotopologues were abundantly detected in non-resonant CID spectra of [M + NH<sub>4</sub>]<sup>+</sup>, [M+Na]<sup>+</sup>, and [M+K]<sup>+</sup>, but not of [M+<sup>85</sup>Rb]<sup>+</sup>. Additional calculations and ERMS logarithmic plots made it possible to rule out a possible <em>endogenous</em> origin of the Rb<sub>2</sub>Cl<sup>+</sup> and Rb<sup>+</sup> isotopologues. They are produced by ion/molecule reactions in the higher-energy collisional dissociation (HCD) cell between ionized cereulide (and b<sub>(12-n)</sub> ions), relaxed by the buffer gas, and neutral RbCl isotopologue salts present in gas phase. The latter are likely generated either during preliminary studies of Rb<sub>n</sub>Cl<sub>(n-1)</sub><sup>+</sup> cluster dissociation in smaller cluster ions and neutral RbCl loss, or from the HCD cell surface by collisions with the buffer gas. Consequently, Rb<sub>2</sub>Cl<sup>+</sup> isotopologues are not precursors of <sup>85</sup>Rb<sup>+</sup> plus <sup>87</sup>Rb<sup>+</sup>.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117513"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-21DOI: 10.1016/j.ijms.2025.117512
Jelle L. Schuurman , Lara van Tetering , Giel Berden , Jos Oomens , Jonathan Martens
The integration of thin-layer chromatography (TLC) with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) provides a fast workflow for the analysis of mixtures. Nevertheless, distinguishing isomers and the structural elucidation of unknown compounds remains challenging and resource intensive. Based on tandem mass spectrometry, infrared ion spectroscopy (IRIS) generates structurally diagnostic vibrational spectra for mass-selected ions confined within a mass spectrometer. By coupling IRIS to the TLC-MALDI-MS workflow, the IR spectra of molecules ionized directly from the TLC plate are obtained. In this study, we separated and identified three isomeric compounds in a mixture through sequential TLC separation, ionization, mass selection and characterization using IRIS. Furthermore, we demonstrate isomer-selective photofragmentation scans of the TLC plate along the axis of separation. This TLC-MALDI-IRIS approach represents a robust, sensitive, and versatile analytical method with broad applications in complex mixture analysis.
{"title":"Structure characterisation using thin-layer chromatography-MALDI MS and infrared ion spectroscopy","authors":"Jelle L. Schuurman , Lara van Tetering , Giel Berden , Jos Oomens , Jonathan Martens","doi":"10.1016/j.ijms.2025.117512","DOIUrl":"10.1016/j.ijms.2025.117512","url":null,"abstract":"<div><div>The integration of thin-layer chromatography (TLC) with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) provides a fast workflow for the analysis of mixtures. Nevertheless, distinguishing isomers and the structural elucidation of unknown compounds remains challenging and resource intensive. Based on tandem mass spectrometry, infrared ion spectroscopy (IRIS) generates structurally diagnostic vibrational spectra for mass-selected ions confined within a mass spectrometer. By coupling IRIS to the TLC-MALDI-MS workflow, the IR spectra of molecules ionized directly from the TLC plate are obtained. In this study, we separated and identified three isomeric compounds in a mixture through sequential TLC separation, ionization, mass selection and characterization using IRIS. Furthermore, we demonstrate isomer-selective photofragmentation scans of the TLC plate along the axis of separation. This TLC-MALDI-IRIS approach represents a robust, sensitive, and versatile analytical method with broad applications in complex mixture analysis.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117512"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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