Control of Intermediates and Products by Combining Droplet Reactions and Ion Soft-Landing.

Despite being recognized primarily as an analytical technique, mass spectrometry also has a large potential as a synthetic tool, enabling access to advanced synthetic routes by reactions in charged microdroplets or ionic thin layers. Such reactions are special and proceed primarily at surfaces of droplets and thin layers. Partial solvation of the reactants is usually considered to play an important role for reducing the activation barrier, but many mechanistic details still need to be clarified. In our study, we showcase the synergy between two sequentially applied "preparative mass spectrometry" methods: initiating accelerated reactions within microdroplets during electrospray ionization to generate gaseous ionic intermediates in high abundance, which are subsequently mass-selected and soft-landed to react with a provided reagent on a substrate. This allows the generation of products at a nanomolar scale, amenable to further characterization. In this proof-of-concept study, the contrasting reaction pathways between intrinsically neutral and pre-charged reagents, respectively, both in microdroplets and in layers generated by ion soft-landing are investigated. This provides new insights into the role of partially solvated reagents at microdroplet surfaces for increased reaction rates. Additionally, further insights into reactions of ions of the same polarity under various conditions is obtained.

Electrochemical Imaging of Precisely-Defined Redox and Reactive Interfaces.

Understanding the diverse electrochemical reactions occurring at electrode-electrolyte interfaces (EEIs) is a critical challenge to developing more efficient energy conversion and storage technologies. Establishing a predictive molecular-level understanding of solid electrolyte interphases (SEIs) is challenging due to the presence of multiple intertwined chemical and electrochemical processes occurring at battery electrodes. Similarly, chemical conversions in reactive electrochemical systems are often influenced by the heterogeneous distribution of active sites, surface defects, and catalyst particle sizes. In this mini review, we highlight an emerging field of interfacial science that isolates the impact of specific chemical species by preparing precisely-defined EEIs and visualizing the reactivity of their individual components using single-entity characterization techniques. We highlight the broad applicability and versatility of these methods, along with current state-of-the-art instrumentation and future opportunities for these approaches to address key scientific challenges related to batteries, chemical separations, and fuel cells. We establish that controlled preparation of well-defined electrodes combined with single entity characterization will be crucial to filling key knowledge gaps and advancing the theories used to describe and predict chemical and physical processes occurring at EEIs and accelerating new materials discovery for energy applications.

The rapid detection of procalcitonin in septic serum using immunoaffinity MALDI chips.

BACKGROUND: Sepsis is a common worldwide health condition with high mortality. It is caused by a dysregulated immune response to the pathogen. Severe infections resulting in sepsis can be also determined by monitoring several bloodstream biomarkers, one of them being pro-hormone procalcitonin (PCT). PCT concentration in the bloodstream correlates well with sepsis and in severe cases increases up to a thousand times from the healthy physiological values in a short time. In this study, we developed a rapid technique for PCT detection by MALDI-TOF mass spectrometry, that uses in-situ enrichment directly on the specialized immuno MALDI chips that are utilized as MALDI plates. The method's ability to detect PCT was confirmed by comparing the results with LC-MS bottom-up workflow. The new method detects intact PCT by its m/z and uncovers its alternations in septic serum. METHODS: The MALDI chips used for the detection of PCT were prepared by ambient ion soft landing of anti-PCT antibody on an ITO glass slide. The chips were used for the development of the rapid MALDI-TOF MS method. A parallel method based on affinity enrichment on magnetic beads followed by LC-MS/MS data-dependent peptide microsequencing was used to prove PCT presence in the sample. All samples were also tested by ELISA to determine PCT concentration prior to analyzing them by mass spectrometry methods. RESULTS: The MALDI chip method was optimized using recombinant PCT spiked into the human serum. The PCT detection limit was 10 ng/mL. The optimized method was used to analyze 13 sera from patients suffering sepsis. The PCT results were confirmed by LC-MS/MS. The measurement of the intact PCT by the MALDI chip method revealed that sera of patients with severe sepsis have other forms of PCT present, which show post-processing of the primary sequence by cleavage of PCT, resulting in the formation of N and C termini fragments. CONCLUSIONS: Procalcitonin from human serum was successfully enriched and detected using immunoaffinity MALDI chips. The intact PCT was characterized in 13 septic patients. The method is more specific compared to non-MS-based immunoaffinity techniques and allows observation of different variants of PCT in septic patients.

Electrochemical and Structural Characterization of Soft Landed Tungsten-Substituted Lindqvist Polyoxovanadate-Alkoxides.

Lindqvist polyoxovanadate-alkoxide (POV-alkoxide) clusters are excellent candidates for applications in energy storage and conversion due to their rich electrochemical profiles. One approach to tune the redox properties of these cluster complexes is through substitutional cationic doping within the hexavanadate core. Here, we report the synthesis of a series of tungsten-substituted POV-alkoxide clusters with one and two tungsten atoms. Soft landing of mass-selected ions was used to purify heterometal POV-alkoxides that cannot be readily separated using conventional approaches. The soft landed POV-alkoxides are characterized using infrared reflection-absorption spectroscopy and electrospray ionization mass spectrometry. The redox properties of the isolated ions are examined using an in situ electrochemical cell which enables traditional in vacuo electrochemical measurements inside of an ion soft landing instrument. Although the overall cluster core retains redox activity after tungsten doping, vanadium-based redox couples (VV /VIV ) are shifted substantially, indicating a pronounced effect of a heteroatom on the electronic structure of the core.

Chemical Synthesis with Gaseous Molecular Ions: Harvesting [B12 Br11 N2 ]- from a Mass Spectrometer.

Mass spectrometry frequently reveals the existence of transient gas phase ions that have not been synthesized in solution or in bulk. These elusive ions are, therefore, often considered to be primarily of analytical value in fundamental gas phase studies. Here, we provide proof-of-concept that the products of ion-molecule reactions in mass spectrometers may be collected on surfaces to generate condensed matter and thus serve as building blocks to synthesize new compounds. The highly reactive fragment anion [B12 Br11 ]- was generated in a mass spectrometer and converted to [B12 Br11 N2 ]- in the presence of molecular nitrogen followed by its mass-selection and soft-landing on surfaces. The molecular structure of [B12 Br11 N2 ]- , which has not been synthetically obtained before, was confirmed by conventional methods of molecular analysis, including nuclear magnetic resonance and infrared spectroscopy. The [B12 Br11 N2 ]- ion is stable on surfaces and in solution at room temperature, but thermal annealing induces elimination of N2 and provides access to the highly reactive intermediate [B12 Br11 ]- in the condensed phase, which can be further used as a reagent, for example, for electrophilic aromatic substitutions. Thus, isolation of [B12 Br11 N2 ]- expands the repertoire of the available diazo ions that can be employed as versatile intermediates in various chemical transformations.

Anion-Anion Chemistry with Mass-Selected Molecular Fragments on Surfaces.

While reactions between ions and neutral molecules in the gas phase have been studied extensively, reactions between molecular ions of same polarity remain relatively unexplored. Herein we show that reactions between fragment ions generated in the gas phase and molecular ions of the same polarity are possible by soft-landing of both reagents on surfaces. The reactive [B12 I11 ]1- anion was deposited on a surface layer built up by landing the generally unreactive [B12 I12 ]2- . Ex-situ analysis of the generated material shows that [B24 I23 ]3- was formed. A computational study shows that the product is metastable in the gas phase, but a charge-balanced environment of a grounded surface may stabilize the triply charged product, as suggested by model calculations. This opens new opportunities for the generation of highly charged clusters using unconventional building blocks from the gas phase.

In situ solid-state electrochemistry of mass-selected ions at well-defined electrode-electrolyte interfaces.

Molecular-level understanding of electrochemical processes occurring at electrode-electrolyte interfaces (EEIs) is key to the rational development of high-performance and sustainable electrochemical technologies. This article reports the development and application of solid-state in situ thin-film electrochemical cells to explore redox and catalytic processes occurring at well-defined EEIs generated using soft-landing (SL) of mass- and charge-selected cluster ions. In situ cells with excellent mass-transfer properties are fabricated using carefully designed nanoporous ionic liquid membranes. SL enables deposition of pure active species that are not obtainable with other techniques onto electrode surfaces with precise control over charge state, composition, and kinetic energy. SL is, therefore, demonstrated to be a unique tool for studying fundamental processes occurring at EEIs. Using an aprotic cell, the effect of charge state ([Formula: see text]) and the contribution of building blocks of Keggin polyoxometalate (POM) clusters to redox processes are characterized by populating EEIs with POM anions generated by electrospray ionization and gas-phase dissociation. Additionally, a proton-conducting cell has been developed to characterize the oxygen reduction activity of bare Pt clusters (Pt30 ∼1 nm diameter), thus demonstrating the capability of the cell for probing catalytic reactions in controlled gaseous environments. By combining the developed in situ electrochemical cell with ion SL we established a versatile method to characterize the EEI in solid-state redox systems and reactive electrochemistry at precisely defined conditions. This capability will advance the molecular-level understanding of processes occurring at EEIs that are critical to many energy-related technologies.

From Isolated Ions to Multilayer Functional Materials Using Ion Soft Landing.

The ability to deposit intact polyatomic ions with well-defined composition, charge state, and kinetic energy onto surfaces makes preparative mass spectrometry, also called ion soft landing, particularly attractive for preparing uniform molecular and ionic layers. Early studies characterized the structures, charge states, and reactivity of sparsely distributed soft-landed species. The recent development of high-flux ionization sources has opened up new opportunities for the precisely controlled preparation of both two-dimensional structures and three-dimensional multilayer architectures by ion soft landing. The deposition of large numbers of ions onto supports led to previously unknown phenomena being uncovered, thereby opening several exciting research directions. Furthermore, faster ion deposition has enabled fabrication of novel functional devices. This Review discusses important phenomena and highlights key developments pertaining to the preparation of well-defined interfaces for studies in energy storage, catalysis, soft materials, and biology.

Writing with Mass-Selected Ions Using a Dynamic Field Wien Filter.

We have designed and constructed a low-cost Wien filter based on strong permanent magnets and integrated it into an ion soft-landing instrument to enable parallel deposition as well as one- and two-dimensional surface patterning of mass-selected ions using dynamic fields. We show the capabilities of this device for separating ions from a multicomponent high-flux continuous ion beam and simultaneous deposition of ions of different mass-to-charge ratios onto discrete locations on a surface. When a dynamic electric field is applied parallel to the magnetic field, ions are deposited in one-dimensional arrays, laterally separated by mass. The field's strength, frequency, and waveform type determine both the lengths of the arrays and the density of ions across the 1-D pattern. Additionally, a second dynamic field from user-defined waveforms orthogonal to the magnetic field enables two-dimensional surface patterning of ions while maintaining mass separation. These experiments demonstrate the practical utility of a Wien filter for the controlled fabrication of interfaces with arbitrary patterns of mass-selected ions.

Coordination-Dependent Chemical Reactivity of TFSI Anions at a Mg Metal Interface.

Charge transfer across the electrode-electrolyte interface is a highly complex and convoluted process involving diverse solvated species with varying structures and compositions. Despite recent advances in in situ and operando interfacial analysis, molecular specific reactivity of solvated species is inaccessible due to a lack of precise control over the interfacial constituents and/or an unclear understanding of their spectroscopic fingerprints. However, such molecular-specific understanding is critical to the rational design of energy-efficient solid-electrolyte interphase layers. We have employed ion soft landing, a versatile and highly controlled method, to prepare well-defined interfaces assembled with selected ions, either as solvated species or as bare ions, with distinguishing molecular precision. Equipped with precise control over interfacial composition, we employed in situ multimodal spectroscopic characterization to unravel the molecular specific reactivity of Mg solvated species comprising (i.e., bis(trifluoromethanesulfonyl)imide, TFSI-) anions and solvent molecules (i.e., dimethoxyethane, DME/G1) on a Mg metal surface relevant to multivalent Mg batteries. In situ multimodal spectroscopic characterization revealed higher reactivity of the undercoordinated solvated species [Mg-TFSI-G1]+ compared to the fully coordinated [Mg-TFSI-(G1)2]+ species or even the bare TFSI-. These results were corroborated by the computed reaction pathways and energy barriers for decomposition of the TFSI- within Mg solvated species relative to bare TFSI-. Finally, we evaluated the TFSI reactivity under electrochemical conditions using Mg(TFSI)2-DME-based phase-separated electrolytes representing different solvated constituents. Based on our multimodal study, we report a detailed understanding of TFSI- decomposition processes as part of coordinated solvated species at a Mg-metal anode that will aid the rational design of improved sustainable electrochemical energy technologies.

Controlled Formation of Fused Metal Chalcogenide Nanoclusters Using Soft Landing of Gaseous Fragment Ions.

The complete ligation of nanoclusters significantly reduces their chemical reactivity, catalytic activity, and charge transfer properties. Therefore, in applications, nanoclusters are activated through partial ligand removal to take advantage of their full potential. However, the precise control of ligand removal in the condensed phase is challenging. In this study, we examine the reactivity of well-defined activated nanoclusters on surfaces prepared through controlled ligand removal in the gas phase. To accomplish this, we utilized a specially designed ion soft-landing instrument equipped with a collision cell to prepare mass-selected fragment ions, which were then deposited onto self-assembled monolayer (SAM) surfaces. Specifically, we generated fragment ions by selectively removing one or two ligands from a series of atomically precise ligated metal sulfide clusters, Co5MS8(L1)6+ (M = Co, Mn, Fe, or Ni, L1 = PEt3). Removal of one ligand from Co5MS8(L1)6+ (M = Co, Mn, Ni) generates Co5MS8(L1)5+ species, which undergo selective dimerization on SAMs. Meanwhile, Co5FeS8(L1)5+ is unreactive and remains intact when it is deposited onto a SAM surface. In contrast, fragments formed by the removal of two ligands, Co5MS8(L1)4+, undergo several nonselective reactions and generate larger fused clusters. We found that the reactivity of the Co5MS8(L1)5+ fragment ions is correlated with the gas phase stability of the corresponding precursor ion toward ligand loss. Specifically, the relatively unstable precursor ion, Co5FeS8(L1)6+, generates the least reactive fragment. Meanwhile, the more stable precursor ions generate more reactive Co5MS8(L1)5+ fragments that dimerize on surfaces. This observation was also confirmed by co-deposition of fragment ions with two different ligands, Co5MS8(L1)5+ and Co5MS8(L2)5+ (L1 = PEt3 and L2 = PEt2Ph), where fragments generated from more stable precursor ions tend to dimerize and generate dimers with mixed ligands. This study unveils the previously unrecognized potential of fragment ions in generating compounds that are difficult to synthesize using conventional methods. Additionally, it provides a mechanistic understanding of the observed reactivity. Mass-selected deposition of well-defined fragment ions emerges as a powerful approach for designing materials by precisely activating and depositing undercoordinated ligated nanoclusters onto surfaces.

Electrolyte Reactivity on the MgV2O4 Cathode Surface.

Predictive understanding of the molecular interaction of electrolyte ions and solvent molecules and their chemical reactivity on electrodes has been a major challenge but is essential for addressing instabilities and surface passivation that occur at the electrode-electrolyte interface of multivalent magnesium batteries. In this work, the isolated intrinsic reactivities of prominent chemical species present in magnesium bis(trifluoromethanesulfonimide) (Mg(TFSI)2) in diglyme (G2) electrolytes, including ionic (TFSI-, [Mg(TFSI)]+, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+) as well as neutral molecules (G2) on a well-defined magnesium vanadate cathode (MgV2O4) surface, have been studied using a combination of first-principles calculations and multimodal spectroscopy analysis. Our calculations show that nonsolvated [Mg(TFSI)]+ is the strongest adsorbing species on the MgV2O4 surface compared with all other ions while partially solvated [Mg(TFSI):G2]+ is the most reactive species. The cleavage of C-S bonds in TFSI- to form CF3- is predicted to be the most desired pathway for all ionic species, which is followed by the cleavage of C-O bonds of G2 to yield CH3+ or OCH3- species. The strong stabilization and electron transfer between ionic electrolyte species and MgV2O4 is found to significantly favor these decomposition reactions on the surface compared with intrinsic gas-phase dissociation. Experimentally, we used state-of-the-art ion soft landing to selectively deposit mass-selected TFSI-, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+ on a MgV2O4 thin film to form a well-defined electrolyte-MgV2O4 interface. Analysis of the soft-landed interface using X-ray photoelectron, X-ray absorption near-edge structure, electron energy-loss spectroscopies, as well as transmission electron microscopy confirmed the presence of decomposition species (e.g., MgFx, carbonates) and the higher amount of MgFx with [Mg(TFSI):G2]+ formed in the interfacial region, which corroborates the theoretical observation. Overall, these results indicate that Mg2+ desolvation results in electrolyte decomposition facilitated by surface adsorption, charge transfer, and the formation of passivating fluorides on the MgV2O4 cathode surface. This work provides the first evidence of the primary mechanisms leading to electrolyte decomposition at high-voltage oxide surfaces in multivalent batteries and suggests that the design of new, anodically stable electrolytes must target systems that facilitate cation desolvation.

Controlling the Activity and Stability of Electrochemical Interfaces Using Atom-by-Atom Metal Substitution of Redox Species.

Understanding the molecular-level properties of electrochemically active ions at operating electrode-electrolyte interfaces (EEI) is key to the rational development of high-performance nanostructured surfaces for applications in energy technology. Herein, an electrochemical cell coupled with ion soft landing is employed to examine the effect of "atom-by-atom" metal substitution on the activity and stability of well-defined redox-active anions, PMo xW12- xO403- ( x = 0, 1, 2, 3, 6, 9, or 12) at nanostructured ionic liquid EEI. A striking observation made by in situ electrochemical measurements and further supported by theoretical calculations is that the substitution of only one to three tungsten atoms by molybdenum atoms in the PW12O403- anions results in a substantial spike in their first reduction potential. Specifically, PMo3W9O403- showed the highest redox activity in both in situ electrochemical measurements and as part of a functional redox supercapacitor device, making it a "super-active redox anion" compared with all other PMo xW12- xO403- species. Electronic structure calculations showed that metal substitution in PMo xW12- xO403- causes the lowest unoccupied molecular orbital (LUMO) to protrude locally, making it the "active site" for reduction of the anion. Several critical factors contribute to the observed trend in redox activity including (i) multiple isomeric structures populated at room temperature, which affect the experimentally determined reduction potential; (ii) substantial decrease of the LUMO energy upon replacement of W atoms with more-electronegative Mo atoms; and (iii) structural relaxation of the reduced species produced after the first reduction step. Our results illustrate a path to achieving superior performance of technologically relevant EEIs in functional nanoscale devices through understanding of the molecular-level electronic properties of specific electroactive species with "atom-by-atom" precision.

Mass Spectrometry for Synthesis and Analysis.

Mass spectrometry is the science and technology of ions. As such, it is concerned with generating ions, measuring their properties, following their reactions, isolating them, and using them to build and transform materials. Instrumentation is an essential element of these activities, and analytical applications are one driving force. Work from the Aston Laboratories at Purdue University's Department of Chemistry is described here, with an emphasis on accelerated reactions of ions in solution and small-scale synthesis; ion/surface collision processes, including surface-induced dissociation (SID) and ion soft landing; and applications to tissue imaging. Our special interest in chirality and the chemistry behind the origins of life is also featured together with the exciting area of tissue diagnostics.