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The continuous effort in making artificial neural networks more alike to human brain calls for the hardware elements to implement biological synapse-like functionalities. The recent experimental demonstration of ferroelectric-like FETs promises low-power operation as compared to the conventional ferroelectric switching devices. This work presents an in-house numerical tool, which self-consistently solves the electrostatics and time-dependent electronic and ionic transport. The tool is exploited to analyze the effect that various physical parameters such as mobility and ion concentration could have on the design of the ferroelectric-like FETs. Their suitability in emulating different functions of the biological synapses is also demonstrated. [ABSTRACT FROM AUTHOR]

Perovskite solar cells (PSCs) continue to be the "front runner" technology among emerging photovoltaic devices in terms of power conversion efficiency and versatility of applications. However, improving stability and understanding their relationship with their ionic–electronic transport mechanisms continue to be challenging. In this work, a case study of NiOx-based inverted PSCs and the effect of different interface passivating treatments on device performance is presented. Impedance spectroscopy (IS) measurements in short-circuit conditions were performed under different illumination intensities, as well as bias-stress operational stability tests under constant illumination intensity. Surface treatments that involved bulky Lewis bases resulted in better and more stable performance. In contrast, acidic anion donors could induce both an initial performance decrease with a characteristic three-arcs impedance Nyquist plot and a subsequent instability during light exposure. Drift–diffusion simulations suggest strong modifications of surface recombination at the interface with the hole transport material, and for the ion concentration and mobilities in the perovskite. Importantly, capacitance and resistance are shown to peak maximum and minimum values, respectively, around mobile ion concentration (Nion) of 1016 and 1017 cm−3. These features relate to the transition from a drift-, for low Nion below a threshold value, to a diffusion-dominated transport in the bulk of the perovskite, for high Nion beyond the threshold value. Our results introduce a general route for characterization of instability paths in PSCs via IS performed under short-circuit conditions. [ABSTRACT FROM AUTHOR]

When electrolyte solutions are confined in micro- and nanochannels their conductivity is significantly different from those in a bulk phase. Here we revisit the theory of this phenomenon by focusing attention on the reduction in the ion mobility with the concentration of salt and a consequent impact to the conductivity of a monovalent solution, from bulk to confined in a narrow slit. We first give a systematic treatment of electrophoresis of ions and obtain equations for their zeta potentials and mobilities. The latter are then used to obtain a simple expression for a bulk conductivity, which is valid in a concentration range up to a few molars and more accurate than prior analytic theories. By extending the formalism to the electrolyte solution in the charged channel the equations describing the conductivity in different modes are presented. They can be regarded as a generalization of prior work on the channel conductivity to a more realistic case of a nonzero reduction of the electrophoretic mobility of ions with salt concentration. Our analysis provides a framework for interpreting measurements on the conductivity of electrolyte solutions in the bulk and in narrow channels. [ABSTRACT FROM AUTHOR]

BaSnF4 is a prospective solid state electrolyte for fluoride ion batteries. However, the diffusion mechanism of the fluoride ions remains difficult to study, both in experiments and in simulations. In principle, ab initio molecular dynamics could allow to fill this gap, but this method remains very costly from the computational point of view. Using machine learning potentials is a promising method that can potentially address the accuracy issues of classical empirical potentials while maintaining high efficiency. In this work, we fitted a dipole polarizable ion model and trained machine learning potential for BaSnF4 and made comprehensive comparisons on the ease of training, accuracy and efficiency. We also compared the results with the case of a simpler ionic system (NaF). We show that contrarily to the latter, for BaSnF4 the machine learning potential offers much higher versatility. The current work lays foundations for the investigation of fluoride ion mobility in BaSnF4 and provides insight on the choice of methods for atomistic simulations. [ABSTRACT FROM AUTHOR]

The subtle structural variations among carbohydrate isomers pose significant challenges for their identification and quantification. Here, we propose a strategy for rapid identification and quantification of isomeric disaccharides via derivatization with 4-(3-methyl-5-oxo-pyrazolin-1-yl) benzoic acid (CPMP) and analysing by ion mobility spectrometry (IMS). After derivatization, the ionization efficiency of disaccharides was significantly improved. The disaccharide isomers were distinguished by determining the different ion mobilities of CPMP-labelled disaccharides. Among them, [M + 2CPMP + H]+ was separated with a resolution of 1.484, almost achieving baseline separation. Subsequently, [M + CPMP + Na]+ was used for the relative quantification of lactose and maltose, showing a good linear relationship with R2 > 0.990. Finally, the method was successfully applied to the identification of lactose and maltose in beer and milk. The method is fast, accurate and effective for the identification of disaccharide isomers in complex samples. [ABSTRACT FROM AUTHOR]

High-resolution ion mobility (resolving power > 200) coupled with mass spectrometry (MS) is a powerful analytical tool for resolving isobars and isomers in complex samples. High-resolution ion mobility is capable of discerning additional structurally distinct features, which are not observed with conventional resolving power ion mobility (IM, resolving power ~ 50) techniques such as traveling wave IM and drift tube ion mobility (DTIM). DTIM in particular is considered to be the "gold standard" IM technique since collision cross section (CCS) values are directly obtained through a first-principles relationship, whereas traveling wave IM techniques require an additional calibration strategy to determine accurate CCS values. In this study, we aim to evaluate the separation capabilities of a traveling wave ion mobility structures for lossless ion manipulation platform integrated with mass spectrometry analysis (SLIM IM-MS) for both lipid isomer standards and complex lipid samples. A cross-platform investigation of seven subclass-specific lipid extracts examined by both DTIM-MS and SLIM IM-MS showed additional features were observed for all lipid extracts when examined under high resolving power IM conditions, with the number of CCS-aligned features that resolve into additional peaks from DTIM-MS to SLIM IM-MS analysis varying between 5 and 50%, depending on the specific lipid sub-class investigated. Lipid CCS values are obtained from SLIM IM (TW(SLIM)CCS) through a two-step calibration procedure to align these measurements to within 2% average bias to reference values obtained via DTIM (DTCCS). A total of 225 lipid features from seven lipid extracts are subsequently identified in the high resolving power IM analysis by a combination of accurate mass-to-charge, CCS, retention time, and linear mobility-mass correlations to curate a high-resolution IM lipid structural atlas. These results emphasize the high isomeric complexity present in lipidomic samples and underscore the need for multiple analytical stages of separation operated at high resolution. [ABSTRACT FROM AUTHOR]

Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies. [ABSTRACT FROM AUTHOR]

The double skeleton interpenetrating network fixed the quaternary ammonium salt, and various internal conduction modes cooperated to promote the transport of hydroxide ions. [Display omitted] The alkaline solid-state electrolytes have received widespread attention for their good safety and electrochemical stability. However, they still suffer from low conductivity and poor mechanical properties. Herein, we report the synthesis of double-network featured hydroxide-conductive membranes fabricated by polyvinyl alcohol (PVA) and chitosan (CS) as the double-skeletons. Then, we implanted quaternary ammonium salt guar hydroxypropyltrimonium chloride (GG) as the OH− conductor for high-performance electrochemical devices. By virtue of the unique stripe-like structure shared from the double skeleton with a high degree of compatibility and stronger hydrogen bond interactions, the polyvinyl alcohol/chitosan-guar hydroxypropyltrimonium chloride (PCG) solid-state electrolytes achieved optimal thermal stability (> 300 °C), mechanical property (∼ 34.15 MPa), dimensional stability (at any bending angle), and high ionic conductivity (13 mS cm−1) and ion mobility number (t ion ∼ 0.90) compared with chitosan-guar hydroxypropyltrimonium chloride (CG) and polyvinyl alcohol-guar hydroxypropyltrimonium chloride (PG) electrolyte membrane. As a proof-of-concept application, the "sandwich"-type zinc-air battery (ZAB) assembled using PCG membrane as the electrolyte realized a high open-circuit voltage (1.39 V) and an excellent power density (128 mW cm−2). Notably, in addition to its long-term cycle life (30 h, 2 mA cm−2) and stable discharge plateau (12 h, 5 mA cm−2), it could even enable a flexible ZAB (F-ZAB) to readily power light-emitting diodes (LED) at any bending angle. These merits afford the PCG membrane a promising electrolyte for improving the performance of solid-state batteries. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDHs) represent a category of two-dimensional layered intercalation materials, showing significant potential as electrode materials for the production of high-energy-density supercapacitors due to their tunable composition, ease of synthetic modification, and low cost. Here, we constructed alkali-etched NiAl LDH-OH nanosheets/Ag nanoparticles (NPs) composite material (Ag@NiAl LDH-OH) for high-performance supercapacitors through a simple solvent-thermal reaction. The alkali treatment is employed to selectively etch some Al3+ ions, generating cation vacancies as active sites for energy storage. Additionally, under the simultaneous influence of strong alkalis and vacancies, the interlayer spacing of LDHs expands, aiding in the promotion of interlayer ion mobility. Meanwhile, the decoration of silver nanoparticles ensures excellent electron conductivity in the NiAl-LDH-OH nanosheets, thereby facilitating improved utilization of the active substance and achieving outstanding rate performance. The Ag@NiAl LDH-OH electrode, when prepared, demonstrates a significant increase in specific capacitance, reaching 1790 F g−1 at a current density of 1 A g−1. This represents approximately 7 times the specific capacitance of the pristine NiAl LDH electrode, with a capacity retention of 79 % even under a high current density of 20 A g−1. Moreover, the assembled asymmetric supercapacitor (ASC) attains a maximum energy density of 138.25 Wh kg−1 at a power density of 700 W kg−1, maintaining 81 % of its initial specific capacitance after 20000 cycles. This research introduces novel pathways for advancing high-energy-density SCs. [ABSTRACT FROM AUTHOR]

Legumain is a cysteine protease broadly associated with inflammation. It has been reported to cleave and activate protease‐activated receptor 2 to provoke pain associated with oral cancer. Outside of gastric and colon cancer, little has been reported on the roles of legumain within the gastrointestinal tract. Using a legumain‐selective activity‐based probe, LE28, we report that legumain is activated within colonocytes and macrophages of the murine colon, and that it is upregulated in models of acute experimental colitis. We demonstrated that loss of legumain activity in colonocytes, either through pharmacological inhibition or gene deletion, had no impact on epithelial permeability in vitro. Moreover, legumain inhibition or deletion had no obvious impacts on symptoms or histological features associated with dextran sulfate sodium‐induced colitis, suggesting its proteolytic activity is dispensable for colitis initiation. To gain insight into potential functions of legumain within the colon, we performed field asymmetric waveform ion mobility spectrometry‐facilitated quantitative proteomics and N‐terminomics analyses on naïve and inflamed colon tissue from wild‐type and legumain‐deficient mice. We identified 16 altered cleavage sites with an asparaginyl endopeptidase signature that may be direct substrates of legumain and a further 16 cleavage sites that may be indirectly mediated by legumain. We also analyzed changes in protein abundance and proteolytic events broadly associated with colitis in the gut, which permitted comparison to recent analyses on mucosal biopsies from patients with inflammatory bowel disease. Collectively, these results shed light on potential functions of legumain and highlight its potential roles in the transition from inflammation to colorectal cancer. [ABSTRACT FROM AUTHOR]

The Journal of Low Temperature Physics published a memorial issue commemorating the life and work of Alexander Fedorovich Andreev, a renowned low-temperature physicist known for his contributions to superconductivity and superfluidity. Andreev's research on Andreev reflection and bound states at interfaces has had a lasting impact on the field. The issue includes articles that build on Andreev's legacy, covering topics such as superconductors, superfluids, quantum crystals, and topological materials, showcasing the breadth of his influence on low-temperature quantum physics. [Extracted from the article]

The study of metal ion's role in the biological processes of Alzheimer's disease has spurred investigations into the coordination chemistry of amyloid beta peptide and its fragments. Nano‐electrospray ionization mass spectrometry (nESI‐MS) has been utilized to examine the stabilization of bound anions on multiprotein complexes without bulk solvent. However, the effects of anions on metal ion binding interactions with amyloid beta peptide have not been explored. This study directly examined metal‐peptide complexes using nESI‐MS and investigated the effects of various anions on the binding ratio and stability of these complexes from ammonium salt solutions. The results indicate that different anions have distinct effects on the binding ratio and stability of various metal‐peptide complexes. Of these, the bicarbonate ion exhibits the highest binding ratios for metal‐peptide complexes, while binding ratios for these complexes in phosphate are comparatively low. Our results suggest that acetate, formate, bicarbonate, and phosphate have weak affinities and act as weak stabilizers of the metal‐peptide complex structure in the gas phase. Intriguingly, chloride and sulfate act as stabilizers of the metal‐peptide complex in the gas phase. The rank order determined from these data is substantially different from the Hofmeister salt series in solution. Although this outcome was anticipated due to the reduced influence of anions and water solvation, our findings correlate well with expected anion binding in solution and emphasize the importance of both hydration layer and anion‐metal‐peptide binding effects for Hofmeister‐type stabilization in solution. This approach proved useful in examining the interactions between metal ions and amyloid beta peptide, which are relevant to Alzheimer's disease, using direct ESI‐MS. [ABSTRACT FROM AUTHOR]

Polystyrene (PS) is a thermoplastic polymer commonly used in various applications due to its bulk properties. Designing functional polystyrenes with well-defined structures for targeted applications is of significant interest due to the rigid and apolar nature of the polymer chain. Progress is hindered to date by the limitations of current analytical methods in defining the atomistic-level folding of the polymer chain. The integration of ion mobility spectrometry and molecular dynamics simulations is beneficial in addressing these challenges. However, data on gas-phase polystyrene ions are rarely reported in the literature. We herein investigate the gas phase structure of polystyrene ions with different end groups to establish how the nature and the rigidity of the monomer unit affect the charge stabilization. We find that, in contrast to polar polymers in which the charges are located deep in the ionic globules, the charges in the PS ions are rather located at the periphery of the polymer backbone, leading to singly and doubly charged PS ions adopting dense elliptic-shaped structures. Molecular dynamics (MD) simulations indicate that the folding of the PS rigid chain is controlled by phenyl ring interactions with the charge ultimately remaining excluded from the core of the globular ions, whereas the folding of polyether ions is initiated by the folding of the flexible polyether chain around the sodium ion that remains deeply enclosed in the core of the ions. [ABSTRACT FROM AUTHOR]

Ion mobility spectroscopy is a technique to characterize compounds based on the differences in the migration of sample ions under the combined action of electric field and air flow. Ions can be separated according to their quantity of electric charge, mass, size and shape. Meanwhile, the collision cross section of the ions can also be calculated to obtain chemical compound structural information, which has shown excellent performance in separating isomers of substances. In recent years, a variety of ion mobility technologies combined with mass spectrometry technology have emerged, and been widely used in food, biology, medicine, environment and other fields. In this paper, the types and working principles of ion mobility spectroscopy are introduced, the advantages and disadvantages of various types of instruments are analyzed, and the application of ion mobility spectrometry, liquid chromatography and mass spectrometry multidimensional combination in analyzing and identifying nutritive and active ingredients and chemical hazards in food is reviewed. The application prospect and development trend of this technology are also prospected. [ABSTRACT FROM AUTHOR]

Complex coacervates play essential roles in various biological processes and applications. Although substantial progress has been made in understanding the molecular interactions driving complex coacervation, the mechanisms stabilizing coacervates against coalescence remain experimentally challenging and not fully elucidated. We recently showed that polydiallyldimethylammonium chloride (PDDA) and adenosine triphosphate (ATP) coacervates stabilize upon their transfer to deionized (DI) water. Here, we perform molecular dynamics simulations of PDDA-ATP coacervates in supernatant and DI water, to understand the ion dynamics and structure within stable coacervates. We found that transferring the coacervates to DI water results in an immediate ejection of a significant fraction of small ions (Na+ and Cl−) from the surface of the coacervates to DI water. We also observed a notable reduction in the mobility of these counterions in coacervates when in DI water, both in the cluster-forming and slab simulations, together with a lowered displacement of PDDA and ATP. These results suggest that the initial ejection of the ions from the coacervates in DI water may induce an interfacial skin layer formation, inhibiting further mobility of ions in the skin layer. Transferring coacervates based on polydiallyldimethylammonium chloride and adenosine triphosphate into deionized water has been experimentally demonstrated to stabilize them against coalescence. Here, molecular modeling and simulations are used to study the coacervation and stabilization of the relevant polyelectrolyte mixture, systematically investigating the structural and dynamic properties that lead to stability. [ABSTRACT FROM AUTHOR]

Developing electrolytes with high Mg2+ ion mobility and compatibility with magnesium electrodes is of the utmost importance for the development of next-generation magnesium ion batteries. Here, we report the findings related to the physicochemical properties of the quasi-solid state chitosan biopolymer electrolyte prepared with a highly polar plastic crystal succinonitrile plasticizer. The prepared biopolymer electrolytes exhibited ionic conductivity in the order of 10−2 S cm−1 which is very much comparable to the conductivity of a liquid electrolyte used in commercial batteries. Besides, the prepared electrolyte shows decreased crystallinity ( χ c ) and glass transition temperature (Tg) values, widened electrochemical window (2.5 V), good transference number ( t Mg 2 + ~0.6), reduced activation energy Ea (25 kJ mol−1), and increased dielectric values (ε). These results confirm the enhanced Mg2+ ion kinetics owing to the addition of SCN with high dissociate property and oxidative stability. Furthermore, the interfacial stability of the best-conducting chitosan biopolymer electrolyte is evaluated using CV analysis against Mg electrodes (vs. Mg/Mg2+). Also, a prototype Mg battery is constructed using the prepared electrolyte, MoO3 cathode, and Mg metal anode which showed an initial specific capacity of 277 mAh g−1 analyzed through galvanostatic charge/discharge studies. Therefore, in light of the results, we believe that adding succinonitrile to polymer electrolytes could be a practical approach to enhancing the electrochemical properties suitable for magnesium ion batteries. [ABSTRACT FROM AUTHOR]

This study focuses on developing a perovskite Li 3x La 2/3-x TiO 3 (LLTO) electrolyte using a simple and effective sol-gel technique. This study aims to enable the hopping of lithium ions in lanthanum sites, which enhances the overall ionic conductivity of the material. By employing an ion conduction mechanism, we investigated the conductivity of powdered and pelletized (dense) LLTO materials. Dense-LLTO exhibits a higher grain ionic conductivity of σ = 1.32 × 10−4 S/cm at room temperature, whereas powdered-LLTO gives a significantly lower conductivity. This significant difference in conductivity can be attributed to the closely packed arrangement of ions in the dense-LLTO structure, which minimizes the evaporation of lithium (Li) in lanthanum (La) sites and promotes ion mobility. Therefore, the thermal treatment process plays a crucial role in facilitating the ion(s) movement and its impact on the ionic conductivity of LLTO, which is mainly influenced by the lithium content. To further evaluate the practical application of LLTO as a solid electrolyte, we constructed a solid-state device with LiFePO 4 /LLTO/AC. The LLTO electrolyte is sandwiched between the activated carbon and LiFePO 4 electrodes. This device exhibits an impressive energy density, achieving 2.42 Wh/kg and a power density of 192 W/kg. Moreover, the device demonstrates better rate capability, allowing for efficient charge and discharge processes. Remarkably, the cyclic stability analysis revealed a retention rate of 92 % over 10,000 cycles, indicating the robustness and durability of the LLTO-based solid-state battery system. These findings highlight the potential of LLTO as a promising solid electrolyte material for advanced energy storage devices. The sol-gel synthesis method provides a simple and effective approach for obtaining high-performance LLTO electrolytes. The enhanced ionic conductivity and excellent electrochemical performance of the solid-state LiFePO 4 /LLTO/AC device demonstrate the feasibility and prospects of LLTO-based batteries in practical applications, offering improved energy density, power density, and long-term cycling stability. [ABSTRACT FROM AUTHOR]

To enhance the performance and widespread use of solid oxide fuel cells (SOFCs), addressing the low-temperature (< 650 °C) electrochemical performance and operational stability issues of cathode materials is crucial. Here, we propose an innovative approach to enhance oxygen ion mobility and electrochemical performance of perovskite oxide by substituting some oxygen sites with chlorine anions. The designed SrTa0.1Fe0.9O3-δ-xClx (x = 0.05 and 0.10) exhibits improved performance compared to SrTa0.1Fe0.9O3-δ (STF). SrTa0.1Fe0.9O2.95-δCl0.05 (STFCl0.05) shows the lowest area-specific resistance (ASR) value on Sm0.2Ce0.8O1.9 (SDC) electrolyte. At 600 °C, STFCl0.05 achieves an ASR value of 0.084 Ω·cm2, and a single cell with STFCl0.05 reaches a higher peak power density (PPD) value (1143 mW·cm-2) than that with STF (672 mW·cm-2). Additionally, besides exhibiting excellent oxygen reduction reaction (ORR) activity at lower temperatures, the STFCl0.05 cathode demonstrates good CO2 tolerance and operational stability. Symmetrical cell operation lasts for 150 h, and single cell operation endures for 720 h without significant performance decline. The chlorine doping approach effectively enhances ORR activity and stability, making STFCl0.05 a promising cathode material for low-temperature SOFCs. [ABSTRACT FROM AUTHOR]

Understanding and controlling the chemical behavior of iron and iron oxide clusters requires accurate thermochemical data, which, because of the complex electronic structure of transition metal clusters, can be difficult to calculate reliably. Here, dissociation energies for Fe 2 + , Fe2O+, and Fe 2 O 2 + are measured using resonance enhanced photodissociation of clusters contained in a cryogenically cooled ion trap. The photodissociation action spectrum of each species exhibits an abrupt onset for the production of Fe+ photofragments from which bond dissociation energies are deduced for Fe 2 + (2.529 ± 0.006 eV), Fe2O+ (3.503 ± 0.006 eV), and Fe 2 O 2 + (4.104 ± 0.006 eV). Using previously measured ionization potentials and electron affinities for Fe and Fe2, bond dissociation energies are determined for Fe2 (0.93 ± 0.01 eV) and Fe 2 − (1.68 ± 0.01 eV). Measured dissociation energies are used to derive heats of formation ΔfH0( Fe 2 + ) = 1344 ± 2 kJ/mol, ΔfH0(Fe2) = 737 ± 2 kJ/mol, ΔfH0( Fe 2 − ) = 649 ± 2 kJ/mol, ΔfH0(Fe2O+) = 1094 ± 2 kJ/mol, and ΔfH0( Fe 2 O 2 + ) = 853 ± 21 kJ/mol. The Fe 2 O 2 + ions studied here are determined to have a ring structure based on drift tube ion mobility measurements prior to their confinement in the cryogenic ion trap. The photodissociation measurements significantly improve the accuracy of basic thermochemical data for these small, fundamental iron and iron oxide clusters. [ABSTRACT FROM AUTHOR]

Polymer cation exchange membranes (CEMs) are widely used in water treatment processes. The fundamental factors that control the separation and selectivity of cations with different valences in CEMs are not fully understood. In this study, we use atomistic molecular dynamics simulations to investigate the underlying molecular mechanisms that control the mobility of cations with different valences in Nafion membranes. Our results indicate structural differences in binding of monovalent and divalent cations, which gives rise to differences in ion diffusion in Nafion. Monovalent cations are shown to be "territorially" bound, i.e., bound while partially hydrated, to the fixed charge groups whereas divalent cations are shown to be "site" bound, i.e., bound while fully dehydrated, to the charge groups on the polymer. This difference in binding structure gives rise to differences in transport characteristics of cations in Nafion. [ABSTRACT FROM AUTHOR]

Ion Mobility coupled with Mass Spectrometry (IM-MS) is a promising analytical technique that enhances molecular characterization by measuring collision cross-section (CCS) values, which are indicative of the molecular size and shape. However, the effective application of CCS values in structural analysis is still constrained by the limited availability of experimental data, necessitating the development of accurate machine learning (ML) models for in silico predictions. In this study, we evaluated state-of-the-art Graph Neural Networks (GNNs), trained to predict CCS values using the largest publicly available dataset to date. Although our results confirm the high accuracy of these models within chemical spaces similar to their training environments, their performance significantly declines when applied to structurally novel regions. This discrepancy raises concerns about the reliability of in silico CCS predictions and underscores the need for releasing further publicly available CCS datasets. To mitigate this, we introduce Mol2CCS which demonstrates how generalization can be partially improved by extending models to account for additional features such as molecular fingerprints, descriptors, and the molecule types. Lastly, we also show how confidence models can support by enhancing the reliability of the CCS estimates. Scientific contribution We have benchmarked state-of-the-art graph neural networks for predicting collision cross section. Our work highlights the accuracy of these models when trained and predicted in similar chemical spaces, but also how their accuracy drops when evaluated in structurally novel regions. Lastly, we conclude by presenting potential approaches to mitigate this issue. [ABSTRACT FROM AUTHOR]

Developing new enantioselective reactions is an important part of chemical discovery but requires time and resources to test large arrays of potential reaction conditions. New techniques are required to analyse many different reactions quickly and efficiently. Mass spectrometry is a high‐throughput method; when combined with ion‐mobility spectrometry, this technique can monitor diastereomeric reaction intermediates and thus be a handle to study enantioselective reactions. Through this technique and others, it was noted before that in the organocatalytic 1,4‐addition to α,β‐unsaturated aldehydes, the abundance of initial diastereomeric intermediates correlates strongly to that of the final enantiomeric products. This work determines isomeric abundance for various catalysts and aldehydes and uses it to predict the enantiomeric excess of two control reactions. The prediction matches well for one reaction but does not predict the obtained results for the second. This finding confirms that the E/Z ratio of the iminium intermediates can be used as a predictor for some reactions, but the kinetics of the following steps can dramatically change the true enantioselectivity. [ABSTRACT FROM AUTHOR]

This study confirms the sodium lauryl sulfate (SLS) surfactant is effective to enhance water electrolysis performance especially when combined with NaCl. The water electrolysis experiment on different concentrations of SLS and SLS-NaCl mixture electrolyte were performed. The results indicate the presence of NaCl is more effective to enhance the SLS containing electrolyte performance instead of adding more SLS concentration. More SLS concentration is effective to enhance hydrogen evolution reaction (HER) when NaCl is added. The effectiveness of NaCl is shown by the order of final HER SLS 0.5 M + NaCl 3.9212 × 10−7 Mol. L−1, SLS 0.3 M + NaCl 3.8789 × 10−7 Mol. L−1, and, SLS 0.5 M 3.6758 × 10−7 Mol. L−1. The SLS creates positively charged micelles which increases ion mobility and HER. The NaCl accelerates the HER due to the formation of smaller ion clusters that react more quickly with the cathode. Therefore, this study reveals the mechanism of electrolysis enhancement by surfactant mixed electrolyte. [Display omitted] • Sodium Lauryl Sulfate (SLS) forms positively charged micelles. • SLS enhances hydrogen evolution reaction (HER) by carry water to cathode. • NaCl ion clusters improves SLS effectiveness to improve HER. • Na ion cluster has better electrostatic response towards cathode. • Cooperation of NaCl and SLS improves overall efficiency. [ABSTRACT FROM AUTHOR]

Current stage of proteomic research in the field of biology, medicine, development of new drugs, population screening, or personalized approaches to therapy dictates the need to analyze large sets of samples within the reasonable experimental time. Until recently, mass spectrometry measurements in proteomics were characterized as unique in identifying and quantifying cellular protein composition, but low throughput, requiring many hours to analyze a single sample. This was in conflict with the dynamics of changes in biological systems at the whole cellular proteome level upon the influence of external and internal factors. Thus, low speed of the whole proteome analysis has become the main factor limiting developments in functional proteomics, where it is necessary to annotate intracellular processes not only in a wide range of conditions, but also over a long period of time. Enormous level of heterogeneity of tissue cells or tumors, even of the same type, dictates the need to analyze biological systems at the level of individual cells. These studies involve obtaining molecular characteristics for tens, if not hundreds of thousands of individual cells, including their whole proteome profiles. Development of mass spectrometry technologies providing high resolution and mass measurement accuracy, predictive chromatography, new methods for peptide separation by ion mobility and processing of proteomic data based on artificial intelligence algorithms have opened a way for significant, if not radical, increase in the throughput of whole proteome analysis and led to implementation of the novel concept of ultrafast proteomics. Work done just in the last few years has demonstrated the proteome-wide analysis throughput of several hundred samples per day at a depth of several thousand proteins, levels unimaginable three or four years ago. The review examines background of these developments, as well as modern methods and approaches that implement ultrafast analysis of the entire proteome. [ABSTRACT FROM AUTHOR]

Chiral analysis is of high interest in many fields such as chemistry, pharmaceuticals and metabolomics. Mass spectrometry and ion mobility spectrometry are useful analytical tools, although they cannot be used as stand-alone methods. Here, we propose an efficient strategy for the enantiomer characterization of amino acids (AAs) using non-covalent copper complexes. A single ion mobility monitoring (SIM2) method was applied on a TIMS-ToF mass spectrometer to maximize the detection and mobility separation of isomers. Almost all of the 19 pairs of proteinogenic AA enantiomers could be separated with at least one combination with the chiral references L-Phe and L-Pro. Furthermore, we extended the targeted SIM2 method by stitching several mobility ranges, in order to be able to analyze complex mixtures in a single acquisition while maintaining high mobility resolution. Most of the enantiomeric pairs of AAs separated with the SIM2 method were also detected with this approach. The SIM2 stitching method thus opens the way to a more comprehensive chiral analysis with TIMS-ToF instruments. [ABSTRACT FROM AUTHOR]

nH-Perfluoroalkyl carboxylic acids (nH-PFCAs) are emerging pollutants. Their identification by ion mobility is frustrated by the nH-PFCAs having unexpectedly small collision cross sections (CCS). Theory and experiment agree that this is because nH-PFCA ions undergo internal hydrogen bridging, and this insight will help guide the creation of more accurate methods for pollutant identification. [ABSTRACT FROM AUTHOR]

We consider the problem of existence and properties of pulse solutions to a system of equations modeling fast calcium waves in long cells. These waves have the speed up to 1000 μ$$ \upmu $$m/s. They propagate via the inflow of calcium ions from the extracellular space through the mechanically stimulated membrane channels. The channels open due to mechano‐chemical interaction, in which stretching of the cell's membrane at a point opens the calcium channels at neighboring points due to the forces exerted by the actomyosin network. The existence of homoclinic solutions is based on the celebrated exchange lemma, which cannot be applied straightforwardly due to some specificities of the model equations. [ABSTRACT FROM AUTHOR]

Materials with high ion mobility are widely used in many fields of modern science and technology. Over the last 40 years, they have thoroughly changed our world. The paper characterizes the structural features of minerals and their synthetic analogs possessing this property. Special attention is paid to the ionic conductors with tetrahedral (zincite- and wurtzite-like), octahedral (ilmenite-like), and mixed (NASICON-like) frameworks. It is emphasized that the main conditions for fast ionic transport are related to the size and positions occupied by a mobile ion, their activation energy, the presence and diameter of conduction channels running inside the structure, isomorphic impurities, and other structural peculiarities. The results of the studies of solid electrolytes are dispersed in different editions, and the overview of new ideas related to their crystal structures was the focus of this paper. [ABSTRACT FROM AUTHOR]

This study established a simple, rapid, and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of contezolid and its major metabolite M2 in human plasma and cerebrospinal fluid (CSF). We used isotope-labeled internal standards (IS) along with protein precipitation to efficiently eliminate impurities. The ion transition was m/z 409.1 → 269.1 for contezolid, m/z 414.1 → 269.0 for contezolid-d5, m/z 445.1 → 385.1 for M2, and m/z 450.2 → 390.1 for M2-d5. The flow rate was 0.4 mL/min with a run time of 2.5 min. Validation results demonstrated that the calibration range was 10–5000 ng/mL for contezolid, and 5–2500 ng/mL for M2 in plasma and CSF. Both analytes exhibit excellent linear relationships (all R2 ≥ 0.99). Intra- and inter-batch accuracy and precision for all quality control (QC) levels were within ± 15%, including the lower limit of quantification (LLOQ). The recoveries of contezolid and M2 were 92.60–100.4% and 92.26–99.61% in plasma and 93.33–99.19% and 91.31–98.21% in CSF, respectively. The matrix effects for contezolid and M2 were 97.20–110.3% and 98.27–105.47% in plasma and 105.25–112.99% and 103.35–109.84% in CSF, respectively. The coefficients of variation (CV%) were ≤ 12.58%. Conteozolid and M2 remained stable in plasma and CSF. This study has established a simple and accurate method for determining contezolid and M2 in human plasma and CSF, making it a valuable tool for monitoring the efficacy of central nervous system (CNS) drugs. [ABSTRACT FROM AUTHOR]

Recently, ion mobility spectrometry‐mass spectrometry (IMS‐MS) has become more readily incorporated into various omics‐based workflows. These growing applications are due to developments in instrumentation within the last decade that have enabled higher‐resolution ion mobility separations. Two such platforms are the cyclic (cIMS) and structures for lossless ion manipulations (SLIM), both of which use traveling wave ion mobility spectrometry (TWIMS). High‐resolution separations achieved with these techniques stem from the drastically increased pathlengths, on the order of 10 s of meters to >1 km, in both cIMS‐MS and SLIM IMS‐MS, respectively. Herein, we highlight recent developments and advances, for the period 2019–2023, in high‐resolution traveling wave‐based IMS‐MS through instrumentation, calibration strategies, hyphenated techniques, and applications. Specifically, we will discuss applications including CCS calculations in multipass IMS‐MS separations, coupling of IMS‐MS with chromatography, imaging, and cryogenic infrared spectroscopy, and isomeric separations of glycans, lipids, and other small metabolites. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) are an important class of biomolecules responsible for the healthy development of the brain‐gut axis of infants. Unfortunately, their accurate characterization is largely precluded due to a variety of reasons – there are over 200 possible HMO structures whereas only 10s of these are available as authentic analytical standards. Furthermore, their isomeric heterogeneity stemming from their many possible glycosidic linkage positions and corresponding α/β anomericities further complicates their analyses. While liquid chromatography coupled to tandem mass spectrometry remains the gold standard for HMO analyses, it often times cannot resolve all possible isomeric species and thus warrants the development of other orthogonal approaches. High‐resolution ion mobility spectrometry coupled to mass spectrometry has emerged as a rapid alternative to condensed‐phase separations but largely has remained limited to qualitative information related to the resolution of isomers. In this work, we have assessed the use of permethylation to improve both the resolution and sensitivity of HMO analyses with cyclic ion mobility separations coupled with mass spectrometry. In addition to this, we have developed the first‐ever high‐resolution collision cross‐section database for permethylated HMOs using our previously established calibration protocol. We envision that this internal reference database generated from high‐resolution cyclic ion mobility spectrometry‐mass spectrometry will greatly aid in the accurate characterization of HMOs and provide a valuable, orthogonal, approach to existing liquid chromatography–tandem mass spectrometry‐based methods. [ABSTRACT FROM AUTHOR]

An ion mobility mass spectrometry (IM‐MS) investigation using a Synapt G2 mass spectrometer was conducted to separate anions generated from the three regioisomers of sulfobenzoic acid. The results revealed that the differences in arrival time distributions (ATDs) were inadequate to differentiate the isomers unambiguously. However, the ATD profiles of the product ions, generated by fragmenting the respective mass‐selected m/z 201 precursor ions in the Trap region of the three‐compartment traveling‐wave ion guide of the Synapt G2 mass spectrometer, were distinctly different, enabling definitive differentiation of the isomers. An arrival‐time peak for an ion of m/z 157 resulting from the loss of CO2 from the respective precursors was common to all three mobilograms. However, only the profile recorded from the para‐isomer exhibited a unique arrival‐time peak for an ion of m/z 137, originating from an SO2 loss. Such a peak corresponding to an SO2 loss was absent in the ATD profiles of the ortho‐ and meta‐isomers. Additionally, the mobilogram of the meta‐isomer displayed a unique peak at 3.42 ms. Based on its product ion spectrum, this peak was attributed to the bisulfite anion (m/z 81; HSO3ˉ). Previously, this meta‐isomer specific m/z 81 ion had been proposed to originate from a two‐step process involving the intermediacy of an m/z 157 ion formed by CO2 loss. However, our detailed tandem mass spectrometric experiments suggest that the m/z 81 is not a secondary product but rather an ion that originated from a direct elimination of a benzyne derivative from the m/z 201 precursor ion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sodium ions inside biomolecular condensates experience heterogeneous dynamics. • An integrative 23Na NMR relaxation-based approach is developed. • This approach allows separating contribution of various sodium ion populations. • Three populations of sodium ions with distinct dynamics detected in agarose gels. Metal ions, including biologically prevalent sodium ions, can modulate electrostatic interactions frequently involved in the stability of condensed compartments in cells. Quantitative characterization of heterogeneous ion dynamics inside biomolecular condensates demands new experimental approaches. Here we develop a 23Na NMR relaxation-based integrative approach to probe dynamics of sodium ions inside agarose gels as a model system. We exploit the electric quadrupole moment of spin-3/2 23Na nuclei and, through combination of single-quantum and triple-quantum-filtered 23Na NMR relaxation methods, disentangle the relaxation contribution of different populations of sodium ions inside gels. Three populations of sodium ions are identified: a population with bi-exponential relaxation representing ions within the slow motion regime and two populations with mono-exponential relaxation but at different rates. Our study demonstrates the dynamical heterogeneity of sodium ions inside agarose gels and presents a new experimental approach for monitoring dynamics of sodium and other spin-3/2 ions (e.g. chloride) in condensed environments. [ABSTRACT FROM AUTHOR]

The chemical looping oxidative dehydrogenation (CL‐ODH) of ethane represents a highly effective approach for converting ethane into the value‐added product ethylene. This investigation focused on the synthesis of SrMnO3 and its halide ions doped derivatives (SrMnO3Cl and SrMnO3Br) through the sol‐gel method. The performance of these perovskites, employed as oxygen carriers in CL‐ODH of ethane, was explored. The results unveiled several advantageous outcomes arising from the incorporation of halide ions (Cl− and Br−) with larger radius into the oxygen sites of the SrMnO3 perovskite. Halide ions doping notably induced cell volume expansion and enhanced lattice fringe spacing. Furthermore, it contributed to elevated oxygen vacancy concentration, increased Mn4+/Mn3+ molar ratio, and improved oxygen ions mobility within the bulk lattice. Fixed‐bed experiments demonstrated that these redox catalysts, doped with halide ions, exhibited outstanding activity and stability during cycling tests, exhibiting enhanced both ethylene selectivity and yield in CL‐ODH of ethane. In summary, the introduction of halide ions into SrMnO3 emerges as a promising strategy for enhancing the performance of CL‐ODH in ethane conversion for SrMnO3 based oxygen carriers. © 2023 Society of Chemical Industry and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Rationale: In soft chemical ionization mass spectrometry, analyte ions are produced via ion–molecule reactions in the reactor. When an electric field E is imposed, the ion drift velocity vd determines the reaction time and the effective ion temperature. Agreement between experimental ion mobilities and theoretical predictions confirms the accuracy of the ion residence time measurement procedure. Methods: A selected ion flow‐drift tube (SIFDT), an instrument with a chemical ionization source, was used to produce protonated aldehydes and selectively inject them into the resistive glass drift tube filled with He. Arrival‐time distributions of ions were obtained using the Hadamard modulation. Reduced ion mobilities were then obtained at a pressure of 2 hPa in the E/N range of 5–15 Td. Theoretical ion mobility values were calculated using two methods: hard‐sphere approximation and trajectory modelling. Results: The measured mobilities of three saturated and three unsaturated protonated aldehydes do not show substantial variation across the studied E/N range. Effective temperatures calculated using the Wannier formula from measured gas temperatures ranged from 300 to 315 K. Experimentally obtained values of the near‐zero‐ E/N‐reduced ion mobilities agree with both methods of calculations typically within ±3% standard deviation (maximum ±5%). Conclusions: The experimental SIFDT values of reduced mobilities in He of protonated aldehyde molecules generated from a chemical ionization source are in close agreement with two different theoretical methods based on the density functional theory calculations of ion geometries and partial atomic charges. Besides its fundamental importance, the ion mobility results validate the correct operation of the drift tube reactor and the ion residence time measurement procedure. Diffusion losses can also be determined from these results. [ABSTRACT FROM AUTHOR]

Background: Q808 is a novel antiepileptic agent currently in development. In this study, we established and validated a LC-MS/MS method for the quantification of Q808 in Rhesus monkey plasma. Furthermore, we applied this method to investigate the pharmacokinetics of Q808 in Rhesus monkeys. Methods: Samples containing diazepam as an internal standard (IS) were subjected to liquid-liquid extraction (LLE) and separated using a Zorbax Extend C18 column. The detection of Q808 and IS was performed using multiple reaction monitoring mode (MRM), specifically monitoring precursor-to-product ion transitions at m/z 297.9 to 213.9 and m/z 285.2 to 193.1 for Q808 and IS, respectively. For the pharmacokinetic study of Q808, a total of 30 healthy Rhesus monkeys (half male and half female) were administered single oral doses, single IV doses, or multiple oral doses of Q808. Blood samples were collected at predetermined time points for subsequent pharmacokinetic analysis. Results: The developed LC-MS/MS method exhibited linearity within the concentration range of 1.5-750 ng/mL with intra-day precision ≤8.3% and inter-day precision ≤14.6%. Additionally, accuracy was found to be ≤3.4%. In the pharmacokinetic study involving single oral doses of Q808 in Rhesus monkeys, Q808 was absorbed with a median time to peak plasma concentration ranging from 4.50-6.00 h and was eliminated with a terminal elimination half-life (t1/2) between 9.34-11.31 h. No definitive conclusion regarding linear pharmacokinetic characteristics could be drawn. The absolute bioavailability was determined as 20.95%, indicating limited systemic exposure after oral administration. Multiple dosing did not result in significant accumulation based on an accumulation factor Rac value of 1.31. Conclusion: We have successfully developed and validated a rapid yet sensitive LC-MS/MS method for quantifying levels of Q808 in rhesus monkey plasma for the first time. The determination method and pharmacokinetic characteristics of Q808 in rhesus monkey support the next steps in drug development. [ABSTRACT FROM AUTHOR]

The development of improved solid electrolytes (SEs) plays a crucial role in the advancement of bulk‐type solid‐state battery (SSB) technologies. In recent years, multicomponent or high‐entropy SEs are gaining increased attention for their advantageous charge‐transport and (electro)chemical properties. However, a comprehensive understanding of how configurational entropy affects ionic conductivity is largely lacking. Herein we investigate a series of multication‐substituted lithium argyrodites with the general formula Li6+x[M1aM2bM3cM4d]S5I, with M being P, Si, Ge, and Sb. Structure‐property relationships related to ion mobility are probed using a combination of diffraction techniques, solid‐state nuclear magnetic resonance spectroscopy, and charge‐transport measurements. We present, to the best of our knowledge, the first experimental evidence of a direct correlation between occupational disorder in the cationic host lattice and lithium transport. By controlling the configurational entropy through compositional design, high bulk ionic conductivities up to 18 mS cm−1 at room temperature are achieved for optimized lithium argyrodites. Our results indicate the possibility of improving ionic conductivity in ceramic ion conductors via entropy engineering, overcoming compositional limitations for the design of advanced electrolytes and opening up new avenues in the field. [ABSTRACT FROM AUTHOR]

The adsorption performance of titanium-based lithium ion sieves for Li+ through H+–Li+ exchange is greatly limited by the pH value of brine. To improve the adsorption capacity of HTO-P (formed titanium-based lithium ion sieves) for Li+, the adsorption characteristics and dynamic performance in Tibetan brine–NaHCO3 (NaHCO3 as a buffer added into the brine used) were studied. The addition of NaHCO3 reduces the aggregation of H+ and maintains the pH value at ∼7.5, which also accelerates the mass transfer rate of Li+ in the initial adsorption stage. Compared with Tibetan brine, the equilibrium adsorption capacity and recovery ratio of HTO-P for Li+ in Tibetan brine–NaHCO3 increase by 60% and 70%, respectively, and the adsorption equilibrium time is shortened by one-third. Moreover, the dynamic saturated adsorption capacity of HTO-P for Li+ reaches 14.25 mg g−1 in Tibetan brine–NaHCO3. This work provides a basis for the direct lithium adsorption and extraction process from salt lake brines. [ABSTRACT FROM AUTHOR]

The measurement of data repeatability in small‐molecule metabolites acquired within and among different liquid chromatography‐mass spectrometry (LC‐MS) platforms is crucial for data sharing or data transfer in natural products research. This work was designed to investigate and evaluate the separation and detection performance of three commercial high‐resolution LC‐MS platforms (e.g., Agilent 6550 QTOF, Waters Vion IM‐QTOF, and Thermo Scientific Orbitrap Exploris 120) using 68 ginsenoside references and the extract of Panax ginseng leaf. The retention time (tR), measured on these three platforms (under the same chromatography condition), showed good stability in different concentration tests, and within/among different instruments for both intra‐day and inter‐day precision examinations. Correlation in tR of ginsenosides was also highly determined on these three platforms. In spite of the different mass analyzers involved, these three platforms gave the accurate mass determination ability, especially enhanced resolution gained because of the ion mobility (IM) separation facilitated by IM‐quadrupole time‐of‐flight. The current study has systematically evaluated the separation and MS detection performance enabled by three high‐resolution LC‐MS platforms taking ginsenosides as the template, and the reported findings can benefit the researchers for the selection of analytical platforms and the purpose of data sharing or data transfer. [ABSTRACT FROM AUTHOR]

Black soldier fly (BSF) melanin is a new supply of the brown-black pigment eumelanin. Given that eumelanin is a model bioelectronic material for applications such as medical devices and sensors, understanding BSF melanin's electrical properties is important to confirm its viability as an advanced material. Presented here is a systematic, hydration dependent alternating current study of BSF melanin utilising both H2O and D2O vapours. There is a clear difference between the vapours, enabling a thorough analysis including Nyquist plots with model circuit analysis, broad band dielectric spectroscopic modelling as well as applying the Trukhan model to understand free ion concentration and mobility changes as a function of hydration. We find that BSF melanin behaves similarly to previous reports on synthetic systems, and the analysis here sheds additional light on potential charge transport changes. Significantly, a key finding is that there are two different mobility mechanisms for ion transport depending on hydration. [ABSTRACT FROM AUTHOR]

Solid flexible separators having adequate ion conductivity at ambient temperature along with good thermal and voltage stability are potential candidates for separators in all solid-state ion batteries. In the present work, zirconium and niobium-doped Li1.3Al0.3Ti1.7 (PO4)3 ceramic particles have been incorporated into a polyvinyl alcohol (PVA) and polyacrylonitrile (PAN)-based blend that served as a flexible matrix to create a flexible polymer–ceramic framework and have been examined for conductivity, dielectric properties, voltage stability, thermal stability, and electrochemical performance. The flexible polymer–ceramic framework shows high thermal stability, improved conductivity, and a high-voltage window. Optimized dc conductivity of 9.8 × 10−5 S cm−1 has been observed among all investigated samples, with an improved voltage stability of 4.94 V. Further, the Trukhan model has been used to understand the effect of filler loading on ion migration properties. The optimized solid polymer electrolyte (SPE) shows improved ion mobility (μ) of 5.13 × 10−2 cm2 V−1 s, number density (n) = 2.39 × 1015 cm³, and diffusion coefficient (D) of 2.09 × 10−3 cm² s−1. It also shows a very high specific capacitance of ~10−4 Fg−1, excellent cycling stability, and 93.75% capacity retention after 100 cycles. [ABSTRACT FROM AUTHOR]

Amyloidosis is a disease characterized by local and systemic extracellular deposition of amyloid protein fibrils where its excessive accumulation in tissues and resistance to degradation can lead to organ failure. Diagnosis is challenging because of approximately 36 different amyloid protein subtypes. Imaging methods like immunohistochemistry and the use of Congo red staining of amyloid proteins for laser capture microdissection combined with liquid chromatography tandem mass spectrometry (LMD/LC–MS/MS) are two diagnostic methods currently used depending on the expertise of the pathology laboratory. Here, we demonstrate a streamlined in situ amyloid peptide spatial mapping by Matrix Assisted Laser Desorption Ionization–Mass Spectrometry Imaging (MALDI-MSI) combined with Trapped Ion Mobility Spectrometry for potential transthyretin (ATTR) amyloidosis subtyping. While we utilized the standard LMD/LC–MS/MS workflow for amyloid subtyping of 31 specimens from different organs, we also evaluated the potential introduction in the MS workflow variations in data acquisition parameters like dynamic exclusion, or testing Data Dependent Acquisition combined with High-Field Asymmetric Waveform Ion Mobility Spectrometry (DDA FAIMS) versus Data Independent Acquisition (DIA) for enhanced amyloid protein identification at shorter acquisition times. We also demonstrate the use of Mascot's Error Tolerant Search and PEAKS de novo sequencing for the sequence variant analysis of amyloidosis specimens. [ABSTRACT FROM AUTHOR]

2-Benzylbenzimidazoles, or "nitazenes", are a class of novel synthetic opioids (NSOs) that are increasingly being detected alongside fentanyl analogs and other opioids in drug overdose cases. Nitazenes can be 20× more potent than fentanyl but are not routinely tested for during postmortem or clinical toxicology drug screens; thus, their prevalence in drug overdose cases may be under-reported. Traditional analytical workflows utilizing liquid chromatography-tandem mass spectrometry (LC–MS/MS) often require additional confirmation with authentic reference standards to identify a novel nitazene. However, additional analytical measurements with ion mobility spectrometry (IMS) may provide a path toward reference-free identification, which would greatly accelerate NSO identification rates in toxicology laboratories. Presented here are the first IMS and collision cross section (CCS) measurements on a set of fourteen nitazene analogs using a structures for lossless ion manipulations (SLIM)-orbitrap MS. All nitazenes exhibited two high intensity baseline-separated IMS distributions, which fentanyls and other drug and druglike compounds also exhibit. Incorporating water into the electrospray ionization (ESI) solution caused the intensities of the higher mobility IMS distributions to increase and the intensities of the lower mobility IMS distributions to decrease. Nitazenes lacking a nitro group at the R1 position exhibited the greatest shifts in signal intensities due to water. Furthermore, IMS-MS/MS experiments showed that the higher mobility IMS distributions of all nitazenes possessing a triethylamine group produced fragment ions with m/z 72, 100, and other low intensity fragments while the lower mobility IMS distributions only produced fragment ions with m/z 72 and 100. The IMS, solvent, and fragmentation studies provide experimental evidence that nitazenes potentially exhibit three gas-phase protomers. The cyclic IMS capability of SLIM was also employed to partially resolve four sets of structurally similar nitazene isomers (e.g., protonitazene/isotonitazene, butonitazene/isobutonitazene/secbutonitazene), showcasing the potential of using high-resolution IMS separations in MS-based workflows for reference-free identification of emerging nitazenes and other NSOs. [ABSTRACT FROM AUTHOR]

Mass-spectrometry based assays in structural biology studies measure either intact or digested proteins. Typically, different mass spectrometers are dedicated for such measurements: those optimized for rapid analysis of peptides or those designed for high molecular weight analysis. A commercial trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) platform is widely utilized for proteomics and metabolomics, with ion mobility providing a separation dimension in addition to liquid chromatography. The ability to perform high-quality native mass spectrometry of protein complexes, however, remains largely uninvestigated. Here, we evaluate a commercial TIMS-Q-TOF platform for analyzing noncovalent protein complexes by utilizing the instrument's full range of ion mobility, MS, and MS/MS (both in-source activation and collision cell CID) capabilities. The TIMS analyzer is able to be tuned gently to yield collision cross sections of native-like complexes comparable to those previously reported on various instrument platforms. In-source activation and collision cell CID were robust for both small and large complexes. TIMS-CID was performed on protein complexes streptavidin (53 kDa), avidin (68 kDa), and cholera toxin B (CTB, 58 kDa). Complexes pyruvate kinase (237 kDa) and GroEL (801 kDa) were beyond the trapping capabilities of the commercial TIMS analyzer, but TOF mass spectra could be acquired. The presented results indicate that the commercial TIMS-Q-TOF platform can be used for both omics and native mass spectrometry applications; however, modifications to the commercial RF drivers for both the TIMS analyzer and quadrupole (currently limited to m/z 3000) are necessary to mobility analyze protein complexes greater than about 60 kDa. [ABSTRACT FROM AUTHOR]

The effect of the sweat and grease deposits (SGD) from fingerprints on the detection efficiency of trace amounts of explosive substances—triacetone triperoxide (TATP), hexamethylene triperoxide diamine (HMTD), and ammonium nitrate (AN) by ion mobility spectrometry in air at atmospheric pressure was investigated. Among the main components of SGD, urea is identified as a positive mode influencer, while lactic acid (LA) affects in a negative mode. The presence of urea or SGD in the sample does not significantly affect the detection of TATP in the positive mode but decreases the efficiency of HMTD ion formation and leads to the appearance of adduct cations of HMTD and urea. The presence of lactic acid or SGD slightly decreases the efficiency of ammonium nitrate ion formation in the negative mode and significantly alters the qualitative composition of HMTD ions, leading to the appearance of HMTD and LA adduct anions. In the absence of any impurities in the sample, the best reduced limit of detection (signal-to-noise ratio = 3σ), estimated at 30–50 pg, was observed for HMTD. The lifetime of HMTD, TATP, and AN traces on aluminum foil under laboratory conditions was determined to be 1, 3, and 12 h for samples with masses of mHMTD 1 × 10–9, 2 × 10–9, and 1 × 10–8 g and surface densities ds of 0.008, 0.016, and 0.08 μg/cm2, respectively; 102 and 103 s for mTATP 1 × 10–5 and 1 × 10–4 g and ds of 80 and 800 μg/cm2, respectively; 12 and 25 h for mAN 3 × 10–8 and 5 × 10–8 g and ds of 0.24 and 0.4 μg/cm2, respectively. [ABSTRACT FROM AUTHOR]

In the realm of quantitative proteomics, data-independent acquisition (DIA) has emerged as a promising approach, offering enhanced reproducibility and quantitative accuracy compared to traditional data-dependent acquisition (DDA) methods. However, the analysis of DIA data is currently hindered by its reliance on project-specific spectral libraries derived from DDA analyses, which not only limits proteome coverage but also proves to be a time-intensive process. To overcome these challenges, we propose ProPept-MT, a novel deep learning-based multi-task prediction model designed to accurately forecast key features such as retention time (RT), ion intensity, and ion mobility (IM). Leveraging advanced techniques such as multi-head attention and BiLSTM for feature extraction, coupled with Nash-MTL for gradient coordination, ProPept-MT demonstrates superior prediction performance. Integrating ion mobility alongside RT, mass-to-charge ratio (m/z), and ion intensity forms 4D proteomics. Then, we outline a comprehensive workflow tailored for 4D DIA proteomics research, integrating the use of 4D in silico libraries predicted by ProPept-MT. Evaluation on a benchmark dataset showcases ProPept-MT's exceptional predictive capabilities, with impressive results including a 99.9% Pearson correlation coefficient (PCC) for RT prediction, a median dot product (DP) of 96.0% for fragment ion intensity prediction, and a 99.3% PCC for IM prediction on the test set. Notably, ProPept-MT manifests efficacy in predicting both unmodified and phosphorylated peptides, underscoring its potential as a valuable tool for constructing high-quality 4D DIA in silico libraries. [ABSTRACT FROM AUTHOR]

Glycans, carbohydrates, and glycoconjugates are involved in many crucial biological processes, such as disease development, immune responses, and cell–cell recognition. Glycans and carbohydrates are known for the large number of isomeric features associated with their structures, making analysis challenging compared with other biomolecules. Mass spectrometry has become the primary method of structural characterization for carbohydrates, glycans, and glycoconjugates. Metal adduction is especially important for the mass spectrometric analysis of carbohydrates and glycans. Metal‐ion adduction to carbohydrates and glycoconjugates affects ion formation and the three‐dimensional, gas‐phase structures. Herein, we discuss how metal‐ion adduction impacts ionization, ion mobility, ion activation and dissociation, and hydrogen/deuterium exchange for carbohydrates and glycoconjugates. We also compare the use of different metals for these various techniques and highlight the value in using metals as charge carriers for these analyses. Finally, we provide recommendations for selecting a metal for analysis of carbohydrate adducts and describe areas for continued research. [ABSTRACT FROM AUTHOR]

Amyloid fibrils, insoluble β‐sheets structures that arise from protein misfolding, are associated with several neurodegenerative disorders. Many small molecules have been investigated to prevent amyloid fibrils from forming; however, there are currently no therapeutics to combat these diseases. Mass spectrometry (MS) is proving to be effective for studying the high order structure (HOS) of aggregating proteins and for determining structural changes accompanying protein–inhibitor interactions. When combined with native MS (nMS), gas‐phase ion mobility, protein footprinting, and chemical cross‐linking, MS can afford regional and sometimes amino acid spatial resolution of the aggregating protein. The spatial resolution is greater than typical low‐resolution spectroscopic, calorimetric, and the traditional ThT fluorescence methods used in amyloid research today. High‐resolution approaches can struggle when investigating protein aggregation, as the proteins exist as complex oligomeric mixtures of many sizes and several conformations or polymorphs. Thus, MS is positioned to complement both high‐ and low‐resolution approaches to studying amyloid fibril formation and protein–inhibitor interactions. This review covers basics in MS paired with ion mobility, continuous hydrogen‐deuterium exchange (continuous HDX), pulsed hydrogen‐deuterium exchange (pulsed HDX), fast photochemical oxidation of proteins (FPOP) and other irreversible labeling methods, and chemical cross‐linking. We then review the applications of these approaches to studying amyloid‐prone proteins with a focus on amyloid beta and alpha‐synuclein. Another focus is the determination of protein–inhibitor interactions. The expectation is that MS will bring new insights to amyloid formation and thereby play an important role to prevent their formation. [ABSTRACT FROM AUTHOR]

Broader adoption of native mass spectrometry (MS) and ion mobility‐mass spectrometry (IM‐MS) has propelled the development of several techniques which take advantage of the selectivity, sensitivity, and speed of MS to make measurements of complex biological molecules in the gas phase. One such method, collision induced unfolding (CIU), has risen to prominence in recent years, due to its well documented capability to detect shifts in structural stability of biological molecules in response to external stimuli (e.g., mutations, stress, non‐covalent interactions, sample conditions etc.). This increase in reported CIU measurements is enabled partly due to advances in IM‐MS instrumentation by vendors, and also innovative method development by researchers. This perspective highlights a few of these advances and concludes with a look forward toward the future of the gas phase unfolding field. [ABSTRACT FROM AUTHOR]