Ion Cyclotron Resonance Cell Research Articles

Structural Characterization of the Metalized Radical Cations of Adenosine ([Ade+Li-H]•+ and [Ade+Na-H]•+) by Infrared Multiphoton Dissociation Spectroscopy and Theoretical Studies.

Nucleoside radicals are key intermediates in the process of DNA damage, and alkali metal ions are a common group of ions in living organisms. However, so far, there has been a significant lack of research on the structural effects of alkali metal ions on nucleoside free radicals. In this study, we report a new method for generating metalized nucleoside radical cations in the gas phase. The radical cations [Ade+M-H]•+ (M = Li, Na) are generated by the 280 nm ultraviolet photodissociation (UVPD) of the precursor ions of lithiated and sodiated ions of 2-iodoadenine in a Fourier transform ion cyclotron resonance (FT ICR) cell. Further infrared multiphoton dissociation (IRMPD) spectra of both radical cations were recorded in the region of 2750-3750 cm-1. By combining these results with theoretical calculations, the most stable isomers of both radicals can be identified, which share the common characteristics of triple coordination patterns of the metal ions. For both radical species, the lowest-energy isomers undergo hydrogen transfer. Although the sugar ring in the most stable isomer of [Ade+Li-H]•+ is in a (South, syn) conformation similar to that of [Ado+Na]+, [Ade+Na-H]•+ is distinguished by the unexpected opening of the sugar ring. Their theoretical spectra are in good agreement with experimental spectra. However, due to the flexibility of the structures and the complexity of their potential energy surfaces, the hydrogen transfer pathways still need to be further studied. Considering that the free radicals formed directly after C-I cleavage have some similar spectral characteristics, the existence of these corresponding isomers cannot be ruled out. The findings imply that the structures of nucleoside radicals may be significantly influenced by the attached alkali metal ions. More detailed experiments and theoretical calculations are still crucial.

Preparation of ultracold ions in strong magnetic field and application to gas-phase NMR spectroscopy II

This paper presents a gas-phase nuclear magnetic resonance (NMR) apparatus, which may enable a tandem combination with an ion cyclotron resonance mass spectrometer. The NMR technique is widely used for analyzing the physical and chemical properties of materials; however, it is mostly limited to materials in condensed phases. Here, we construct a gas-phase NMR apparatus to extend this technique to gas-phase molecular ions. We outline the principle of NMR detection based on a Stern-Gerlach-type experiment and describe the experimental procedures and results for the preparation and manipulation of ultracold ions, which are fundamental for the proposed NMR detection. The development of the gas-phase NMR probe and radio-frequency excitation system and the features of the apparatus are presented. We also discuss the feasibility of combining this apparatus with an ion cyclotron resonance cell for realizing an NMR apparatus for mass-selected molecular ions briefly.

Fourier transform ion cyclotron resonance mass spectrometry at the true cyclotron frequency.

Ion cyclotron resonance (ICR) cells provide stability and coherence of ion oscillations in crossed electric and magnetic fields over extended periods of time. Using the Fourier transform enables precise measurements of ion oscillation frequencies. These precisely measured frequencies are converted into highly accurate mass-to-charge ratios of the analyte ions by calibration procedures. In terms of resolution and mass accuracy, Fourier transform ICR mass spectrometry (FT-ICR MS) offers the highest performance of any MS technology. This is reflected in its wide range of applications. However, in the most challenging MS application, for example, imaging, enhancements in the mass accuracy of fluctuating ion fluxes are required to continue advancing the field. One approach is to shift the ion signal power into the peak corresponding to the true cyclotron frequency instead of the reduced cyclotron frequency peak. The benefits of measuring the true cyclotron frequency include increased tolerance to electric fields within the ICR cell, which enhances frequency measurement precision. As a result, many attempts to implement this mode of FT-ICR MS operation have occurred. Examples of true cyclotron frequency measurements include detection of magnetron inter-harmonics of the reduced cyclotron frequency (i.e., the sidebands), trapping field-free (i.e., screened) ICR cells, and hyperbolic ICR cells with quadrupolar ion detection. More recently, ICR cells with spatially distributed ion clouds have demonstrated attractive performance characteristics for true cyclotron frequency ion detection. Here, we review the corresponding developments in FT-ICR MS over the past 40 years.

Potential of Fourier Transform Mass Spectrometry (Orbitrap and Ion Cyclotron Resonance) for Speciation of the Selenium Metabolome in Selenium-Rich Yeast.

The evolution of the field of element speciation, from the targeted analysis for specific element species toward a global exploratory analysis for the entirety of metal- or metalloid-related compounds present in a biological system (metallomics), requires instrumental techniques with increasing selectivity and sensitivity. The selectivity of hyphenated techniques, combining chromatography, and capillary electrophoresis with element-specific detection (usually inductively coupled plasma mass spectrometry, ICP MS), is often insufficient to discriminate all the species of a given element in a sample. The necessary degree of specificity can be attained by ultrahigh-resolution (R >100,000 in the m/z < 1,000 range for a 1 s scan) mass spectrometry based on the Fourier transformation of an image current of the ions moving in an Orbitrap or an ion cyclotron resonance (ICR) cell. The latest developments, allowing the separate detection of two ions differing by a mass of one electron (0.5 mDa) and the measurement of their masses with a sub-ppm accuracy, make it possible to produce comprehensive lists of the element species present in a biological sample. Moreover, the increasing capacities of multistage fragmentation often allow their de novo identification. This perspective paper critically discusses the potential state-of-the-art of implementation, and challenges in front of FT (Orbitrap and ICR) MS for a large-scale speciation analysis using, as example, the case of the metabolism of selenium by yeast.

Evaluation of major historical ICR cell designs using electric field simulations.

In Fourier‐transform ion cyclotron resonance mass spectrometry, ions are detected by measuring image current induced in the detecting electrodes by trapped ions rotating in a magnetic field at their cyclotron frequencies. The ion trap used for this purpose is called the Penning trap. It can have various configurations of electrodes that are used to create a trapping electric field, to excite cyclotron motion, and to detect the induced signal. The evolution of this type of mass spectrometry is mainly driven by progress in the technology of superconducting magnets and in the constantly improved design of the ion cyclotron resonance (ICR) measuring cell. In this review, we focus on ICR cell designs. We consider that the driving forces of this evolution are the desire to increase resolution, mass accuracy and dynamic range, as well as to adapt new methods for creating and trapping ions.

Optimization of ion trajectories in a dynamically harmonized Fourier-transform ion cyclotron resonance cell using a design of experiments strategy.

With the recent introduction of the dynamically harmonized Fourier-transform ion cyclotron resonance (FT-ICR) cell, the complexity of tuning has expanded drastically, and fine-tuning of the direct current voltages is required to optimize the ion cloud movement. As this adjustment must typically be performed manually, more reliable computational methods would be useful. Here we propose a computational method based on a design of experiments (DoE) strategy to overcome the limits of classical manual tuning. This DoE strategy was exemplarily applied on a 12 T FT-ICR instrument equipped with a dynamically harmonized ICR cell. The chemometric approach, based on a central composite face (CCF) design, was first applied to a reference material (sodium trifluoroacetate) allowing for the evaluation of the primary cell parameters. Eight factors related to shimming and gating were identified. The summed intensity of the signal corresponding to the even harmonics was defined as one quality criterion. The DoE response allowed for rapid and complete mapping of cell parameters resulting in an optimized parameter set. The new set of cell parameters was applied to the study of an ultra-complex sample: Tholins, an ultra-complex mixture that mimics the haze present on Titan, was chosen. We observed a substantial improvement in mass spectrometric performance. The sum of signals related to harmonics was decreased by a factor of three (from 4% for conventional tuning to 1.3%). Furthermore, the dynamic range was also increased, which in turn led to an increase in attributed peaks by 13%. This computational procedure based on an experimental design can be applied to any other mass spectrometric parameter optimization problem. This strategy will lead to a more transparent and data-driven method development.

Infrared Spectroscopy of Size-Selected Hydrated Carbon Dioxide Radical Anions CO2 .- (H2 O)n (n=2-61) in the C-O Stretch Region.

Understanding the intrinsic properties of the hydrated carbon dioxide radical anions CO2 .−(H2O)n is relevant for electrochemical carbon dioxide functionalization. CO2 .−(H2O)n (n=2–61) is investigated by using infrared action spectroscopy in the 1150–2220 cm−1 region in an ICR (ion cyclotron resonance) cell cooled to T=80 K. The spectra show an absorption band around 1280 cm−1, which is assigned to the symmetric C−O stretching vibration ν s. It blueshifts with increasing cluster size, reaching the bulk value, within the experimental linewidth, for n=20. The antisymmetric C−O vibration ν as is strongly coupled with the water bending mode ν 2, causing a broad feature at approximately 1650 cm−1. For larger clusters, an additional broad and weak band appears above 1900 cm−1 similar to bulk water, which is assigned to a combination band of water bending and libration modes. Quantum chemical calculations provide insight into the interaction of CO2 .− with the hydrogen‐bonding network.

Extracting biomolecule collision cross sections from FT-ICR mass spectral line shape

To extend the ion structure analysis capability of Fourier transform mass spectrometry (FT-MS), both time-domain and frequency-domain methods have been developed to extract ion collision cross sections (CCS) from high resolution mass spectra in Fourier transform ion cyclotron resonance (FT-ICR) cells. In this study, a new frequency-domain method, namely the line shape fitting method, was proposed to calculate ion CCSs from FT-ICR mass spectra line shape. Besides experimental data, simulated data with precisely controlled signal to noise levels and decay factors were also applied to characterize this method. Compared with the linewidth correction method previously proposed by our group, this line shape fitting method is more tolerant to noise, data length, and sampling rate, thus providing more consistent results. More importantly, CCS measurements of angiotensin I, bradykinin, ubiquitin and cytochrome c show that the resolving power is improved with the new method.

Potential of dynamically harmonized Fourier transform ion cyclotron resonance cell for high-throughput metabolomics fingerprinting: control of data quality.

Due to the presence of pollutants in the environment and food, the assessment of human exposure is required. This necessitates high-throughput approaches enabling large-scale analysis and, as a consequence, the use of high-performance analytical instruments to obtain highly informative metabolomic profiles. In this study, direct introduction mass spectrometry (DIMS) was performed using aFourier transform ion cyclotron resonance (FT-ICR) instrument equipped with a dynamically harmonized cell. Data quality was evaluated based on mass resolving power (RP), mass measurement accuracy, and ion intensity drifts from the repeated injections of quality control sample (QC) along the analytical process. The large DIMS data size entails the use of bioinformatic tools for the automatic selection of common ions found in all QC injections and for robustness assessment and correction of eventual technical drifts. RP values greater than 106 and mass measurement accuracy of lower than 1ppm were obtained using broadband mode resulting in the detection of isotopic fine structure. Hence, a very accurate relative isotopic mass defect (RΔm) value was calculated. This reduces significantly the number of elemental composition (EC) candidates and greatly improves compound annotation. A very satisfactory estimate of repeatability of both peak intensity and mass measurement was demonstrated. Although, a non negligible ion intensity drift was observed for negative ion mode data, a normalization procedure was easily applied to correct this phenomenon. This study illustrates the performance and robustness of the dynamically harmonized FT-ICR cell to perform large-scale high-throughput metabolomic analyses in routine conditions. Graphical abstract Analytical performance of FT-ICR instrument equipped with a dynamically harmonized cell.

Multiparticle Simulations of Quadrupolar Ion Detection in an Ion Cyclotron Resonance Cell with Four Narrow Aperture Detection Electrodes.

The current paradigm in FT-ICR cell design is to approximate the ideal three-dimensional quadratic trapping potential as closely as possible to maintain ion cloud spatial coherence and achieve long transients, either with hyperbolically shaped electrodes, shimming electrodes, or by dynamic harmonization. In sharp contrast, the FT-ICR analyzer cell with four narrow aperture detection electrodes (NADEL) introduces significant anharmonic terms to the trapping potential. This analyzer cell is capable of quadrupolar detection by which one can measure a signal that is close to the unperturbed cyclotron frequency. This is far less sensitive to trapping potential and space charge shifts than the reduced cyclotron frequency measured in conventional ICR cells. The quadrupolar mode of ion detection in NADEL cells has been examined previously by SIMION simulations of ion clouds with up to 500 ions per simulation. Here, the behavior of the NADEL analyzer cell is examined through particle-in-cell (PIC) simulations, which allows us to examine the behavior of large populations (tens of thousands) of ions with space charge considerations, and to calculate the induced charge on the NADEL detection electrodes, and thus the transient signal. PIC simulations confirm a unique spatial distribution of the ions, with a coherent motion that results in long transient signals. Dependence of the ion cloud and image current signal on cell design, ion energy, and magnetron radius are examined. Coalescence effects are compared with those found in a dynamically harmonized cell. The insensitivity of the measured cyclotron frequency to space-charge is demonstrated both with simulations and experimentally. Graphical Abstract ᅟ.

Effect of ion clouds micromotion on measured signal in Fourier transform ion cyclotron resonance: Computer simulation.

Particle-in-cell-based realistic simulation of Fourier transform ion cyclotron resonance experiments could be used to generate ion trajectories and a signal induced on the detection electrodes. It has been shown recently that there is a modulation of "reduced" cyclotron frequencies in ion cyclotron resonance signal caused by Coulomb interaction of ion clouds. In this work it was proposed to use this modulation in order to determine frequency difference between an ion of known m/z and all other ions generating signal in ion cyclotron resonance cell. It is shown that with an increase of number of ions in ion cyclotron resonance trap, the modulation index increases, which lead to a decrease in the accuracy of determination of peak intensities by super Fourier transform resolution methods such as filter diagonalization method.

Static harmonization of dynamically harmonized Fourier transform ion cyclotron resonance cell.

Static harmonization in the Fourier transform ion cyclotron resonance cell improves the resolving power of the cell and prevents dephasing of the ion cloud in the case of any trajectory of the charged particle, not necessarily axisymmetric cyclotron (as opposed to dynamic harmonization). We reveal that the Fourier transform ion cyclotron resonance cell with dynamic harmonization (paracell) is proved to be statically harmonized. The volume of the statically harmonized potential distribution increases with an increase in the number of trap segments.

Parallel Spectral Acquisition with Orthogonal ICR Cells.

FT-based high performance mass analyzers yield increased resolving power and mass measurement accuracy, yet require increased duration of signal acquisition that can limit many applications. The implementation of stronger magnetic fields, multiple detection electrodes for harmonic signal detection, and an array of multiple mass analyzers arranged along the magnetic field axis have been used to decrease required acquisition time. The results presented here show that multiple ion cyclotron resonance (ICR) mass analyzers can also be implemented orthogonal to the central magnetic field axis. The orthogonal ICR cell system presented here consisting of two cells (master and slave cells) was constructed with printed circuit boards and installed within a single superconducting magnet and vacuum system. A master cell was positioned, as is normally done with ICR cells, on the central magnetic field axis and a slave cell was located off this central axis, but directly adjacent and alongside the master cell. To achieve ion transfer between cells, ions that were initially trapped in the master cell were drifted across the magnetic field into the slave cell with application of a small DC field applied perpendicularly to the magnetic field axis. A subsequent population of ions was injected and accumulated in the master cell. Simultaneous excitation of cyclotron motion of ions in both cells was carried out; ICR signals from each cell were independently amplified and recorded in parallel. Presented here are the initial results of successful parallel spectral acquisition with this orthogonal dual ICR cell array. Graphical Abstract ᅟ.

Experimental Basicities of Phosphazene, Guanidinophosphazene, and Proton Sponge Superbases in the Gas Phase and Solution.

Experimental gas-phase superbasicity scale spanning 20 orders of magnitude and ranging from bicyclic guanidine 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene to triguanidinophosphazenes and P3 phosphazenes is presented together with solution basicity data in acetonitrile and tetrahydrofuran. The most basic compound in the scale-triguanidinophosphazene Et-N═P[N═C(NMe2)2]3-has the highest experimental gas-phase basicity of an organic base ever reported: 273.9 kcal mol(-1). The scale includes besides the higher homologues of classical superbasic phosphazenes and several guanidino-substituted phosphazenes also a number of recently introduced bisphosphazene and bis-guanidino proton sponges. This advancement was made possible by a newly designed Fourier transform ion cyclotron resonance (ICR) mass spectrometry setup with the unique ability to generate and control in the ICR cell sufficient vapor pressures of two delicate compounds having low volatility, which enables determining their basicity difference. The obtained experimental gas-phase and solution basicity data are analyzed in terms of structural and solvent effects and compared with data from theoretical calculations.

The Role of Ultrahigh Resolution Fourier Transform Mass Spectrometry (FT-MS) in Astrobiology-Related Research: Analysis of Meteorites and Tholins.

It is an important but also a challenging analytical problem to understand the chemical composition and structure of prebiotic organic matter that is present in extraterrestrial materials. Its formation, evolution and content in the building blocks (“seeds”) for more complex molecules, such as proteins and DNA, are key questions in the field of exobiology. Ultrahigh resolution mass spectrometry is one of the best analytical techniques that can be applied because it provides reliable information on the chemical composition and structure of individual components of complex organic mixtures. Prebiotic organic material is delivered to Earth by meteorites or generated in laboratories in simulation (model) experiments that mimic space or atmospheric conditions. Recent representative examples for ultrahigh resolution mass spectrometry studies using Fourier-transform (FT) mass spectrometers such as Orbitrap and ion cyclotron resonance (ICR) mass spectrometers are shown and discussed in the present article, including: (i) the analysis of organic matter of meteorites; (ii) modeling atmospheric processes in ICR cells; and (iii) the structural analysis of laboratory made tholins that might be present in the atmosphere and surface of Saturn’s largest moon, Titan.

Vacuum Ultraviolet Photodissociation and Fourier Transform-Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited.

We revisited the implementation of 193 nm ultraviolet photodissociation (UVPD) within the ion cyclotron resonance (ICR) cell of a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and proteins within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing, relative to ion magnetron motion and the potential applied to an ion optical element upon which photons impinge. It is shown that UVPD yields efficient and extensive fragmentation, resulting in excellent sequence coverage for model peptide and protein cations.

Parallel Spectral Acquisition with an Ion Cyclotron Resonance Cell Array.

Mass measurement accuracy is a critical analytical figure-of-merit in most areas of mass spectrometry application. However, the time required for acquisition of high-resolution, high mass accuracy data limits many applications and is an aspect under continual pressure for development. Current efforts target implementation of higher electrostatic and magnetic fields because ion oscillatory frequencies increase linearly with field strength. As such, the time required for spectral acquisition of a given resolving power and mass accuracy decreases linearly with increasing fields. Mass spectrometer developments to include multiple high-resolution detectors that can be operated in parallel could further decrease the acquisition time by a factor of n, the number of detectors. Efforts described here resulted in development of an instrument with a set of Fourier transform ion cyclotron resonance (ICR) cells as detectors that constitute the first MS array capable of parallel high-resolution spectral acquisition. ICR cell array systems consisting of three or five cells were constructed with printed circuit boards and installed within a single superconducting magnet and vacuum system. Independent ion populations were injected and trapped within each cell in the array. Upon filling the array, all ions in all cells were simultaneously excited and ICR signals from each cell were independently amplified and recorded in parallel. Presented here are the initial results of successful parallel spectral acquisition, parallel mass spectrometry (MS) and MS/MS measurements, and parallel high-resolution acquisition with the MS array system.

An optical spectrum of a large isolated gas-phase PAH cation: C78H[formula omitted

A gas-phase optical spectrum of a large polycyclic aromatic hydrocarbon (PAH) cation - C78H26+− in the 410−610 nm range is presented. This large all-benzenoid PAH should be large enough to be stable with respect to photodissociation in the harsh conditions prevailing in the interstellar medium (ISM). The spectrum is obtained via multi-photon dissociation (MPD) spectroscopy of cationic C78H26 stored in the Fourier Transform Ion Cyclotron Resonance (FT-ICR) cell of the PIRENEA setup using the radiation from a mid-band optical parametric oscillator (OPO) laser.The experimental spectrum shows two main absorption peaks at 431 nm and 516 nm, in good agreement with a theoretical spectrum computed via time-dependent density functional theory (TD-DFT). DFT calculations indicate that the equilibrium geometry, with the absolute minimum energy, is of lowered, nonplanar C2 symmetry instead of the more symmetric planar D2h symmetry that is usually the minimum for similar PAHs of smaller size. This kind of slightly broken symmetry could produce some of the fine structure observed in some diffuse interstellar bands (DIBs). It can also favor the folding of C78H26+ fragments and ultimately the formation of fullerenes.This study opens up the possibility to identify the most promising candidates for DIBs amongst large cationic PAHs.

Collision cross section measurements for biomolecules within a high-resolution Fourier transform ion cyclotron resonance cell.

To understand the role and function of a biomolecule in a biosystem, it is important to know both its composition and structure. Here, a mass spectrometric based approach has been proposed and applied to demonstrate that collision cross sections and high-resolution mass spectra of biomolecule ions may be obtained simultaneously by Fourier transform ion cyclotron resonance mass spectrometry. With this method, the unfolding phenomena for ubiquitin ions that possess different number of charges have been investigated, and results agree well with ion mobility measurements. In the present approach, we extend ion collision cross-section measurements to lower pressures than in prior ion cyclotron resonance (ICR)-based experiments, thereby maintaining the potentially high resolution of Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), and enabling collision cross section (CCS) measurements for high-mass biomolecules.

Collision cross section measurements for biomolecules within a high-resolution FT-ICR cell: theory.

In this study, an energetic hard-sphere ion-neutral collision model was proposed to bridge-link ion collision cross section (CCS) with the image current collected from a high-resolution Fourier transform ion cyclotron resonance (FT-ICR) cell. By investigating the nonlinear effects induced by high-order electric fields and image charge forces, the energetic hard-sphere collision model was validated through experiments. Suitable application regions for the energetic hard-sphere collision model, as well as for the conventional Langevin and hard-sphere collision models, were also discussed. The energetic hard-sphere collision model was applied in the extraction of ion CCSs from high-resolution FT-ICR mass spectra. Discussions in the present study also apply to FT-Orbitraps and FT-quadrupole ion traps.