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Analysis of samples of exhaled breath condensate (EBC) is a promising noninvasive method for the control of the status of the human respiratory system. In the present work, the proteome of the EBC samples received from a patient with lung dystrophy at different times before and after bilateral lung transplantation is analyzed by ion cyclotron resonance mass spectrometry. Qualitative protein composition of EBC samples obtained during the first month correlates with the clinical data on the acceptance of the transplanted lungs (allograft). Fifteen months after the lung surgery, the protein spectrum was similar to the normal composition of EBC proteins. This result agrees with the medical conclusion about normal lung functioning. The results suggest that the mass spectrometric monitoring of the protein spectra of EBC may be a tool for noninvasive pulmonological diagnostics.

Peak coalescence, i.e. the merging of two close peaks in a Fourier transform ion cyclotron resonance (FTICR) mass spectrum at a high number of ions, plays an important role in various FTICR experiments. In order to describe the coalescence phenomenon we would like to propose a new theory of motion for ion clouds with close mass-to-charge ratios, driven by a uniform magnetic field and Coulomb interactions between the clouds. We describe the motion of the ion clouds in terms of their averaged drift motion in crossed magnetic and electric fields. The ion clouds are considered to be of constant size and their motion is studied in two dimensions. The theory deals with the first-order approximation of the equations of motion in relation to dm/m, where dm is the mass difference and m is the mass of a single ion. The analysis was done for an arbitrary inter-cloud interaction potential, which makes it possible to analyze finite-size ion clouds of any shape. The final analytical expression for the condition of the onset of coalescence is found for the case of uniformly charged spheres. An algorithm for finding this condition for an arbitrary interaction potential is proposed. The critical number of ions for the peak coalescence to take place is shown to depend quadratically on the magnetic field strength and to be proportional to the cyclotron radius and inversely proportional to the ion masses.

The peptide RHDSGY, a fragment of the human β-amyloid Zn-binding site, and its isomers RH(D-Asp)SGY and RH(β-Asp)SGY have been obtained as amides by means of solid-phase synthesis and analyzed by HPLC and various mass spectrometric methods. The problem of low yield of the RHDSGY peptide and its isomers attributed to 9-fluorenylmethoxycarbonyl (Fmoc)-amino acids and/or formation of such side-products as RH(β-Asp)SGY (or RHDSGY during synthesis of RH(β-Asp)SGY) and RH(Asp-imide) SGY was solved via selection of individual reagents for removal of Fmoc groups from α-amino groups of the growing peptide chain.

An ideally quadratic potential used in different types of ion mass analyzer such as Paul trap, Kingdon trap and quadratic field reflectron may be space-periodically disturbed due to inaccuracy of fabrication and design features. If ion motion in such devices is computer-simulated, disturbances of potential may be caused by the peculiarity of the computation method. The problem investigated in this work is the effect that weak space-periodic disturbance of a quadratic potential takes on the ion motion in such a potential. The effect of the disturbance we considered is the misphasing of an ion cloud oscillating in a disturbed quadratic potential. A method to evaluate the characteristic misphasing time is presented. For the case of disturbance amplitude being constant along ion trajectories, the designated problem may be considered analytically. If the disturbance amplitude depends on oscillation co-ordinate, the result can be obtained by use of numerical integration. An example of numerical calculation is presented.

We explored a possibility of using atmospheric pressure ionization techniques like corona discharge chemical ionization and surface thermoionization for distinguishing the chiral chemical compounds in situ. In both cases of ionization techniques we used home built ion sources coupled with non-modified ThermoFinnigan interfaces. For the proof-of-principle demonstration of recognition of molecule chirality in situ we used dimethyltartrate as a model chiral substance. We demonstrated that both ionization methods produce dimers and trimers of the dimethyltartrate molecules with pronounced chiral discrimination effects. In the case of corona discharge ionization we detected H3O+ and H2O+ based dimers and trimers. K+ based dimers and trimers dominated the mass spectra in the case of thermoionization. Homochiral domination in the potassiumated dimers and H2O+ based dimers can be attributed to inherited chirality effect from the trimers. We showed that addition of the water molecules to dimers strongly influenced the effect of chirality on dimer stability by making heterochiral dimer more stable than homochiral in case of addition of one water molecule and removing the influence of chirality on dimers stability by addition of two or more water molecules. The experimental observations agree well with the results of the quantum chemical calculation obtained for dimers containing different number of water molecules.

A highly sensitive method for the quantitative determination of a potential antiarrhythmic drug (OF-7976) in the blood plasma has been developed. The method is based on the electron spray ionization/mass spectrometry (ESI-MS) technique without preliminary chromatographic separation and makes use of nibentan as the internal standard. A linear relationship between drug concentration and the peak intensity of ions of the analyzed substance (m/z = 398) and the internal standard (m/z = 382) is established. The detection limit is 3 ng/(0.5 ml plasma). The method is linear from 3 to 25 ng/(0.5 ml plasma) with a correlation coefficient of 0.98. The coefficient of variation was less than 7 %.

Chronic imbalance between production and degradation of the human amyloid-beta peptide (Abeta) is assumed to play an important role in pathogenesis of Alzheimer's disease (AD). Post-translational modifications of Abeta could influence its interactions with specifically cleaving proteases and, therefore, perturb the Abeta homeostasis. The angiotensin-converting enzyme (ACE) was previously shown to degrade non-modified Abeta in vitro and in cells. In the presented work, we investigated the effect of isomerization of Asp-7, a common non-enzymatic age-related modification found in AD-associated Abeta species, on hydrolysis of Abeta by ACE. Two synthetic peptides corresponding to the Abeta region 1-16 with either Asp or isoAsp residues in position 7 were examined as monomeric soluble substrates for the N- as well as for the C-domain of ACE. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) coupled with the (18)O-labeled internal standard approach has allowed us to show that (i) the N-domain of ACE (N-ACE), but not the C-domain, selectively cleaves the Arg-5-His-6 bond in both peptides, and that (ii) N-ACE hydrolyzes the isoAsp-7 analogue more efficiently than the non-modified one. Our results demonstrate a new endopeptidase activity of N-ACE as well as high preference of the domain to recognize and hydrolyze the isomerized Abeta species that were earlier suggested to promote AD pathogenesis. The results suggest the need for further analysis of biological effects of isomerized Abeta and its interaction with ACE in AD pathogenesis.

Isotopic exchange approach coupled to high-resolution mass spectrometry has become the power analytical approach for a wide range of analytical and bioanalytical applications. Considerable efforts have been dedicated to developing fast exchange techniques directly in the ionization source. But all such methods are limited to the hydrogen/deuterium exchange approaches. In this paper we demonstrate that certain types of oxygen atoms can also be exchanged for 18O on the time scale of the ionization process. Using HIO3 and NaIO4 and by infusing the heavy water H218O in the ESI source we have demonstrated that it is possible to obtain a high level of oxygen exchange. It was observed that the rate of this exchange depends to a large extent on the temperature of the desolvating capillary of the mass spectrometer. Several other species, such as peptides, oligonucleotides and low weight organic molecules, were subjected to in-ESI 16O/18O exchange but the exchange was not observed.

Real-time feedback about dissected tissue during the neurosurgical procedure is strongly requested. A novel direct ionization mass spectrometric method for identifying pathological differences in tissues is proposed. The method is based on simultaneous extraction of tissue lipids and electrospray ionization which allows mass spectrometric data to be obtained directly from soft tissues. The advantage of this method is the stable flow of solvent, which leads to stable time-dependent spectra. The tissues included necrotized tissues and tumor tissues in different combinations. Capability for direct analysis of samples of dissected tissues during the neurosurgical procedure is demonstrated. Data validation is conducted by compound identification using precise masses from the MS profile, MS/MS, and isotopic distribution structure analysis. The method can be upgraded and applied for real-time identification of tissues during surgery. This paper describes the technique and its application perspective. For these purposes, other methods were compared with the investigated one and the results were shown to be reproducible. Differences in lipid profiles were observed even in tissues from one patient where distinctions between different samples could be poor. The paper presents a proof of concept for the method to be applied in neurosurgery particularly and in tissue analysis generically. The paper also contains preliminary results proving the possibility of observing differences in mass spectra of different tumors.

The products of the oxidative coupling of phenols are frequently used as synthetic analogues to natural humic substances (HS) for biomedical research. However, their molecular compositions and exact structures remain largely unknown. The objective of this study was to develop a novel approach for the molecular-level analysis of phenolic polymerisates that is capable of inventorying molecular constituents and resolving their distinct structural formulas. For this purpose, we have synthesized the model HS using the oxidative coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3-methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the synthesized model HS using high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the model HS. The assigned molecular formulas occupied the substantial space of CHO compositions in the Van Krevelen diagram with a maximum density found in the regions of tannins and lignins, resembling those of natural HS. To identify the exact structural formulas of the individual constituents in the model HS, we have applied selective H/D exchange of non-labile backbone protons by a choice of basic or acidic catalytic conditions followed by FTICR MS. The determined formulas allowed us to verify the proposed pathways of hydroxylation and carboxylation in the course of the phenolic coupling and to identify the acetylation of aromatic rings as an important side reaction. We conclude that the proposed analytical approach may be used to identify the molecular carriers of biological activity within the phenolic polymerisates and eventually within natural HS.

A model for the drift of ions under a non-uniform, high-frequency electric field in the drift chamber of a spectrometer of ion mobility increment is developed. For the general dependence of the ion mobility on the electric field strength and the general time-dependence of the separating voltage, we suggest a procedure for calculating of the ion peak form. The shape of the peak for the ion focusing and defocusing conditions has been obtained.

Determination of the hepatitis C virus (HCV) genotype has become accepted as the standard procedure in laboratory practice. Genotype assignment helps in disease prognosis and assists in establishing the appropriate duration of treatment. More than 10 types and 70 subtypes of HCV have been described. In Russia the most common subtypes are 1a, 1b, 2a, and 3a, and the types 4 and 5 are relatively rare. The “gold standard” for testing is gene sequencing. However, a variety of other assays had been developed to provide more rapid and cheaper forms of testing. The aim of this study was to determine the HCV genotype by minisequencing followed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Fragments of 5′ untranslated region of the HCV genome were amplified. Three oligonucleotide primers were designed to detect two sets of genotype-specific single nucleotide polymorphisms. The primer extension reaction was performed using modified thermostable DNA polymerase and in the presence of dideoxynucleosides. The molecular weights of the reaction products were analyzed with MALDI-TOF mass spectrometer. The HCV genotype was determined by registering the particles of the expected molecular weights. The method was used to genotype HCV from HCV-positive blood sera or plasma. The 1a, 1b, 2a, 3a, and 4 genotype HCVs were determined in the samples examined. The data were confirmed by direct sequencing. Thus, we propose a new accurate and efficient method for HCV genotyping based on minisequencing followed by mass spectrometry.

An experimental approach for increasing the efficiency of Electron Capture Dissociation (ECD) with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) is presented. The approach is based on manipulating the spatial distribution of an ion cloud inside an FTICR trap during electron irradiation, which is realized by using both on-resonance pre-excitation of the ions and sustained off-resonance irradiation (SORI). The achieved fragmentation efficiency is compared with the theoretical prediction. This method may be useful in biological applications of FTICR, such as identification of posttranslational modifications in proteins and de novo sequencing, where the ECD technique is most applicable.

The process of fission of charged liquid droplets is an important stage of multiply charged ion formation in the electrospray ionization (ESI) process. ESI is currently the most powerful ionization method in the mass spectrometry of large molecules such as biopolymers. Fission plays a crucial role in the ion formation essentially in the range of nanosized droplets, since it determines the charge states of product ions. Usually the Rayleigh equation is used to determine critical conditions, at which the fission process takes place. This equation gives the value of the critical radius of the charged droplet as a function of its charge and specific surface energy. The Rayleigh equation does not give us the opportunity to determine charges and sizes of the fission fragments. In the present work we propose a mathematical model that describes the fission process of the charged liquid droplet in an external electrostatic field. The model is based on the quasi-equilibrium assumption that the most probable shape of the droplet corresponds to the minimum of the free energy of the system. The change in the internal kinetic energy and dissipative losses for the viscous liquid are also taken into account in the model.

Ion motion in a periodic radio frequency (RF) quadrupole electric field is analysed theoretically by the matrix method and direct trajectory calculation. General properties of the ion motion: stability condition, oscillation spectrum and secular frequency are derived analytically from the elements of the transformation matrix. Stability diagrams for ion motion in the Paul ion trap are presented for rectangular waveforms with different duty cycles (duration of pulse over period). Calculation of the secular frequencies of the ion motion in the ion trap is performed for the first time. The relation of radial and axial secular frequencies along the RF scan line was found to be practically identical in both the square waveform and harmonic voltage cases. Pulse shape distortions, due to resistive-inductive-capacitive filtering in real devices, are considered. Stability diagrams of ion motion in the ion trap with distorted voltage waveforms are calculated. Distortion of the waveform is shown to introduce minor changes in the diagram shape with respect to the diagram for an ideal square wave. Within the first stable region, distortion of the waveform does not lead to any auxiliary parametric resonances of the ion motion. Ion trapping with a pure random pulsed voltage is investigated by means of direct trajectory simulations. It is shown that, in this case, the ion motion can be conditionally stable for a considerable length of time.

Collision-induced dissociation (CID) of alanine or phenylalanine aggregates with various cations, including the proton, alkali metal ions, calcium and zinc, as well as the transition metals Co(II), Ni(II) and Cu(II), has been studied by tandem mass spectrometry. In these experiments, an isotopically labeled, chirally-pure amino acid (L-Ala-d3 and L-Phe-d5) is mixed with its unlabeled enantiomer and a metal salt and the clusters generated by electrospray ionization are mass-selected and subjected to CID. The relative stability of the precursor ions, as well as product-ion abundance ratios in the tandem mass spectra, are used as indicators of chiral effects on the dissociation process. It is shown that the stability of alanine aggregates during the kinetic dissociation process is independent of chirality, whereas a large chiral effect ( Rchiral ranging from 0.31 to 8.1) is observed for the clusters assembled from phenylalanine and transition metal ions. When two bulky phenylalanine molecules are covalently bound to a metal ion, the heterochiral cluster is more stable than the homochiral one. Clusters containing three or four phenylalanine molecules are loosely bound to the core ion and the homochiral cluster is more stable than the heterochiral one. It is suggested that non-covalent interactions, in particular π-cation interactions, are significant contributors to the large chiral effects. It is further suggested that the relationship between the branching ratio in the tandem mass spectrum and chirality can be used to determine the absolute configuration of chiral molecules.

There are two physical processes that influence the spatial distribution of transcription factor molecules entering the nucleus of a eukaryotic cell, the binding to genomic DNA and the diffusion throughout the nuclear volume. Comparison of the DNA-protein association rate constant and the protein diffusion constant may determine which one is the limiting factor. If the process is diffusion-limited, transcription factor molecules are captured by DNA before their even distribution in the nuclear volume. Otherwise, if the reaction rate is limiting, these molecules diffuse evenly and then find their binding sites. Using well-studied human NF-κB dimer as an example, we calculated its diffusion constant using the Debye-Smoluchowski equation. The value of diffusion constant was about 10(-15) cm(3)/s, and it was comparable to the NF-κB association rate constant for DNA binding known from previous studies. Thus, both diffusion and DNA binding play an equally important role in NF-κB spatial distribution. The importance of genome 3D-structure in gene expression regulation and possible dependence of gene expression on the local concentration of open chromatin can be hypothesized from our theoretical estimate.

The objectives of this study were to identify molecular features characteristic to arctic DOM from the Kolyma River basin and to elucidate structural imprints induced by a choice of the sorption technique. To achieve this goal, DOM was isolated from the Kolyma River basin with a use of three nonionic sorbents: Amberlite XAD-8 resin, PPL- and C18 - SPE cartridges, and one anion exchanging resin-diethylaminoethyl (DEAE) -cellulose. The structural studies were conducted with a use of electrospray ionization Fourier Transform Ion Cyclotron Resonance (ESI FT-ICR) mass spectrometry and liquid state (1)H NMR spectroscopy. The DOM isolates obtained with a use of PPL and C18 cartridges were characterized with higher content of aliphatic compounds as compared to XAD-8 and DEAE-isolates. In total, for all arctic DOM isolates we observed predominance of hydrogen saturated compounds with high H/C values of identified formulas from FT-ICR MS data. (1)H NMR spectroscopy studies have confirmed this trend and revealed high contribution of alkyl-chain protons into the spectral density of the arctic DOM reaching 43% for PPL isolates.

We analyzed protein profile of urine samples obtained from 7 Russian cosmonauts (age 35-51 years), participants of space flights on the International Space Station lasting for 169-199 days. Gradient chromatography with linear increase of eluent proportion was carried out in a system consisting of an Agilent 1100 chromatograph (Agilent Technologies Inc.) and a hybrid mass-spectrometer LTQ-FT Ultra (Thermo). The obtained results help to understand changes in the human body induced by space flight factors.

Chiral recognition of d- and l-amino acids is achieved and mixtures of enantiomers quantified in the gas phase, using the kinetics of competitive unimolecular fragmentations of trimeric Cu(II)-bound complexes. Singly charged copper(II)−amino acid cluster ions [CuII(A)(ref*)2−H]+ (A = amino acid; ref* = chiral reference ligand, selected from among the natural α-amino acids) undergo competitive collision-induced dissociation (CID) in a quadrupole ion trap to form the dimeric complexes [CuII(A)(ref*)−H]+ and [CuII(ref*)2−H]+. The abundance ratio of these fragment ions depends strongly on the stereochemistry of the ligands in the precursor [CuII(A)(ref*)2−H]+ complex ion and specifically on the chirality of the analyte amino acid. The chiral selectivity, the ratio of the two fragment ion abundances for the complex containing one enantiomer of analyte expressed relative to that for the fragments of the corresponding complex containing the other enantiomer, ranges from 0.47 to 11. An energy quantity, Δ(ΔCuIIBDE...

A Bruker 7 T Fourier transform (FT) mass spectrometer fitted with electron impact (EI) and electrospray ionization (ESI) external ion sources has been modified for surface-induced dissociation (SID) studies utilizing a self-assembled monolayer (SAM) of CF3(CF2)9C2H4SH alkanethiolate chemisorbed on gold. Operational aspects of ion sources, intermediate hexapole ion storage, time-of-flight function of the ion optics and cell trapping mechanisms are discussed for both primary and secondary ions. Different methods of ion trapping in the FT ion cyclotron resonance cell were analyzed theoretically and dynamic voltage trapping (DVT) was chosen as the most suitable. Direct measurements of primary (short time scale) and secondary (delayed) SID fragmentation and kinetic energy distributions of the SID fragments illustrate the capabilities of the instrument as a research tool for investigating SID kinetics. SID of small molecules and model peptides was investigated over a moderate collision energy range and the ion population was sampled at various decomposition delay times. Kinetic energy distributions of SID fragment ions were measured and shown to be quite low over the range of energies investigated. Most of the primary ion kinetic energy is dissipated into surface excitation and internal energy of ions recoiled from the surface.

Simple glycine-based peptides containing acidic [aspartic (D) and glutamic acid (E)] and basic residues [arginine (R)] were dissociated by surface-induced dissociation (SID) both in a tandem double quadrupole (Q1Q2) and a hybrid sector/time-of-flight (TOF) mass spectrometer, as well as by low-energy collision-induced dissociation in an ion trap mass spectrometer. The synthetic peptides investigated were G D GGG D G, G D GGG D GR, RG D GGG D G, RG D GGG D GR, GGG D GR, GGG E GR, and G D GGG E GR. The mass spectral results obtained support and extend our previous findings that selective cleavages at the C–(O)–N bond adjacent to the acidic residues (C-side) predominate in the spectra when the number of ionizing protons equals or is less than the number of arginine residues. They also support our conclusion that these cleavages are induced by the side-chain acidic hydrogens of D or E residues. Stochastic molecular modeling procedures have been employed in this work to probe the gas-phase conformations for these protonated peptides. These searches have revealed possible conformers of singly protonated GGG D GR, and RG D GGG D G peptide ions where the protonated arginine is solvated by nearby carboxylic and carbonyl oxygens along with simultaneous intramolecular H bonding between the D side-chain acidic hydrogen(s) and the adjacent C-side peptide bonds. Electrospray ionization/surface-induced dissociation fragmentation efficiency curves (percent fragmentation versus SID laboratory collision energy) are also presented for some of these peptides. The relative position of these curves both with the Q1Q2 and sector/TOF instruments along with less pronounced selective cleavages for the E-containing peptides support our previous conclusion that selective cleavage at E residues require longer time frames for dissociation than for D-containing peptides. The total sum of these findings underscores the idea that gas-phase secondary structure (i.e. conformation) can have an influence in peptide fragmentation.

Electrospray ionization of equimolar solutions of S-dimethyl tartrate and R-d6-dimethyl tartrate in methanol/water/acetic acid/salt solutions was utilized to investigate molecular recognition processes in solution. Pronounced chirality effects previously reported for formation of the protonated dimer by ion molecule reactions in the gas phase are quantitatively reproduced in experiments which sample solution phase protonated dimers. Ab initio quantum calculations demonstrate that hydrogen bonds in the protonated cluster are responsible for molecular recognition and that Li+ bound clusters, which do not exhibit chiral recognition, are primarily bound by electrostatic forces. In contrast with gas phase studies of alkali and ammonium ion core dimers of dimethyl tartrate—which show no chirality effects—ions electrosprayed from solutions containing trace amounts of these ions show pronounced chirality. With increasing salt concentration the apparent chirality effect disappears and a statistical distribution identical to that found for the gas phase is obtained. These observations are rationalized by a kinetic model that considers the displacement of protons by alkali ions in the final stages of desolvation of microdroplets formed in the electrospray process.

A method to enumerate labile hydrogens in all constituents of molecular ensemble of natural organic matter (NOM) based on our previously developed simple hydrogen/deuterium (H/D) exchange (electrospray ionization (ESI) ion source (Kostyukevich et al. Anal. Chem. 2013, 85, 5330) and ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry is presented. The method was applied for analysis of Suwannee River fulvic acid (SRFA), which is an International Humic Substances Society standard, as well as Siberian crude oil; and lignosulfonate. We found that SRFA and lignosulfonate molecules contain 2–5 labile hydrogens, and their number increases with the number of oxygens in the molecule. Also, we observed that compounds of Siberian crude oil ionizing in positive-ESI mode do not have labile hydrogens, while compounds ionizing in negative-ESI mode have one labile hydrogen that detaches during ESI ionization.

Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer offers highest resolving power and mass accuracy among all types of mass spectrometers. Its unique analytical characteristics made FT ICR important tool for proteomics, metabolomics, petroleomics, and investigation of complex mixtures. Signal acquisition in FT ICR MS takes long time (up to minutes). During this time ion-ion interaction considerably affects ion motion and result in decreasing of the resolving power. Understanding of those effects required complicated theory and supercomputer simulations but culminated in the invention of the ion trap with dynamic harmonization which demonstrated the highest resolving power ever achieved. In this review we summarize latest achievements in theory and simulation of FT ICR mass spectrometers.

Understanding of the behavior of ion ensembles inside an FT ICR cell based on the computer simulations of ion motion gives rise to new ideas on cell design. The novel recently introduced FT-ICR cell based on a Penning ion trap with specially shaped excitation and detection electrodes prevents distortion of ion cyclotron motion phases (normally caused by non-ideal electric trapping fields) by averaging the trapping DC electric field during ion motion in the ICR cell. Detection times of up to 5 minutes resulting in resolving power close to 40,000,000 have been reached for reserpine at m/z 609 at a magnetic field of only 7 Tesla. The fine structure of resolved 13Cn isotopic cluster groups could be measured for molecular masses of up to 5.7 kDa (insulin) with the resolving power of 4,000,000 at 7 Tesla. Based on the resolved fine structure patterns the atomic composition can be directly determined using a new developed algorithm for fine structure processing. Mass spectra of proteins and multimers of proteins reaching masses of up to 186 kDa (enolase tetramer) could be measured with isotopic resolution. For instance, at 7 Tesla the resolving power of 800,000 was achieved for the enolase dimer (96kDa) and 500,000 for molecular masses above 100 kDa. Experimental data indicates that there is practically no limit for the resolving power of this ICR cell except for collisional damping in the ultrahigh vacuum chamber. Dynamic range limits caused by Ion cloud-cloud collision is discussed. Collision of ion clouds with each other is a significant factor determining the dynamic range of the FT-ICR MS resulting in a loss of close oscillation phases for high ion densities. In most FT-ICR experiments ions were exited to close cyclotron orbits, so the ion clouds come through each other with a frequency equal to the difference of their cyclotron frequencies. Therefore the dynamic range in FT-ICR experiments could be increased by exciting different m/z ion clouds to different cyclotron radii.

The form of FTMS signals is analyzed for the general case of multiple electrode ICR cells with detailed results for two, eight and sixteen electrodes. The analysis is based on an elongated cylindrical cell to reduce the problem of treating the electric field distribution to two dimensions. The relative contributions of cyclotron and magnetron motion to the detected signal are analyzed for multiple electrode detection to establish the conditions for maximizing high order harmonic detection as a strategy for simultaneously enhancing mass resolution and sensitivity for characterizing high mass ions in FTMS. For pure cyclotron motion (no magnetron motion) only the basic frequency and its odd harmonics are detected by two electrodes; for multiple electrodes the transformed frequencies (originating from the commutation effect) and their odd harmonics are detected. The relative intensities of harmonic signals are greatly enhanced in large orbits, which also maximize the signal strength. Good agreement between the modeled FTMS signal and experimental results for a sixteen electrode ICR cell is demonstrated. The general conclusion is that minimization of magnetron motion is required for simplification and optimization of the FTMS signal with multiple electrode detection. This is entirely feasible with current technology and is a useful strategy for significantly enhancing mass resolution and S/N ratio in FTMS.

Four mumijo samples originated from different mountain ranges were studied using size-exclusion chromatography (SEC), Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), and 1H and 13C NMR spectroscopy. All the used analytical techniques demonstrated that the mumijo samples studied consist of a “high-molecular” fulvic-like and a low-molecular components. The second component is shown using FTICR MS and NMR methods to be predominantly a range of vegetative and animal metabolites.

The factors responsible for temporal variation of the detected frequency in an FT ion cyclotron resonance (ICR) spectrometer are analysed. The time-dependent frequency behaviour is believed to be caused by a change in ion cloud configuration, the number of detected ions, and the ion cloud position in the electric field of the ICR cell. The spectral peak shape is calculated for an ensemble of non-interacting ions distributed over amplitudes of axial oscillations. The influence of the Coulomb interaction on the signal and the spectral peak shape is studied by a computer simulation using a highly parallel computer.

A new technique for the capture of external ions by an FT-ICR ion trap is suggested. Ions produced from atoms of low ionization energy collide with one of the trapping electrodes of the ICR cell, lose energy without neutralization and are captured. The surface of the trapping electrode must have a high enough work function. The probability of ion capture was investigated as a function of the ion energy and cell geometry parameters.

Isotopomeric quasi-racemates (IQR), i.e., 1:1 mixtures of enantiomers one of which contains an isotopic label, can undergo crystallisation as conglomerates or true quasi-racemates. In the former case, each single crystal contains, predominantly or exclusively, either labelled or non-labelled enantiomers, whereas in the latter case, it contains both enantiomers (1:1). If solution sputtering is used to ionise quasi-racemates, the formation of homochiral protonated and metallated enantiomers and their homo-chiral oligomers in the gas phase is detected in ion cyclotron resonance (ICR) mass spectra; these compounds differ in their m/z values; hence, Pasteur-like 'manual sorting' can be employed to catch them successively in the ion trap of the spectrometer.

The recently designed dynamically harmonized Fourier transform ion cyclotron resonance (FT-ICR) cell creates a more harmonized electric field for the detection of the cyclotron motion of ions and prolongs the ion transient from seconds to minutes. In order to achieve its best performance, phase correction was applied in the spectra, and new advantages of the absorption-mode were revealed.Spectra were acquired from both simple standard and complex mixtures using either narrowband or broadband mode, and the data were processed to compare the performance of the spectra in magnitude and absorption-mode.The research shows that phase correction works well with data from Nikolaev's new cell, which produces the maximum improvement in resolving power (2×), and improves the match with the theoretical intensities of the isotopic peaks. In addition, the harmonic peaks can be diagnosed immediately in the absorption-mode.The manuscript demonstrates absorption-mode spectra from Nikolaev's ICR cell, which will be of interest to the community. The improved relative peak intensities and immediate identification of harmonic peaks will facilitate data interpretation.

The resolving power of the low energy ion scattering technique with FT-ICR spectrometry is discussed. Resolution improvement due to simultaneous registration of scattered ions with different masses is shown.

The orbital trap mass analyzer provides a number of unique analytical features along with inevitable limitations as an electrostatic instrument operating in high space charge regimes resulting in systematic measured frequency errors as an effect of stored ion clouds on the trap field and each other effect of non-ideal machining the trap electrodes, effect of injection slot, effect of real versus theoretical trap dimensions, etc. This paper deals with determining the influence of the space charge effect and imperfection of the electrostatic field on the motion of ion ensembles in the orbital trap. We examine effects of theoretically modeled non-harmonicity of the electrostatic potential and the number of confined ions on stability of coherent ion motion in the trap that determines the frequency shifts of axial ion oscillation. Three different Orbitrap geometries were considered: geometry close to preproduction Orbitrap, close to standard Orbitrap, close to high field Orbitrap. Frequency shifts for m/z = 500 and for charge state +23 of cytochrome c isotopic cluster particles with 10(4)-6*10(6) elemental charges in the trap were considered. Refined spectra were calculated using the filter diagonalization method proposed by Mandelshtam et al. and applied to mass spectrometry by O'Connor and Aizikov.

Particle-in-Cell (PIC) ion trajectory calculations provide the most realistic simulation of Fourier transform ion cyclotron resonance (FT-ICR) experiments by efficient and accurate calculation of the forces acting on each ion in an ensemble (cloud), including Coulomb interactions (space charge), the electric field of the ICR trap electrodes, image charges on the trap electrodes, the magnetic field, and collisions with neutral gas molecules. It has been shown recently that ion cloud collective behavior is required to generate an FT-ICR signal and that two main phenomena influence mass resolution and dynamic range. The first is formation of an ellipsoidal ion cloud (termed "condensation") at a critical ion number (density), which facilitates signal generation in an FT-ICR cell of arbitrary geometry because the condensed cloud behaves as a quasi-ion. The second phenomenon is peak coalescence. Ion resonances that are closely spaced in m/z coalesce into one resonance if the ion number (density) exceeds a threshold that depends on magnetic field strength, ion cyclotron radius, ion masses and mass difference, and ion initial spatial distribution. These two phenomena decrease dynamic range by rapid cloud dephasing at small ion density and by cloud coalescence at high ion density. Here, we use PIC simulations to quantitate the dependence of coalescence on each critical parameter. Transitions between independent and coalesced motion were observed in a series of the experiments that systematically varied ion number, magnetic field strength, ion radius, ion m/z, ion m/z difference, and ion initial spatial distribution (the present simulations begin from elliptically-shaped ion clouds with constant ion density distribution). Our simulations show that mass resolution is constant at a given magnetic field strength with increasing ion number until a critical value (N) is reached. N dependence on magnetic field strength, cyclotron radius, ion mass, and difference between ion masses was determined for two ion ensembles of different m/z, equal abundance, and equal cyclotron radius. We find that N and dynamic range depend quadratically on magnetic field strength in the range 1-21 Tesla. Dependences on cyclotron radius and Δm/z are linear. N depends on m/z as (m/z)(-2). Empirical expressions for mass resolution as a function of each of the experimental parameters are presented. Here, we provide the first exposition of the origin and extent of trade-off between FT-ICR MS dynamic range and mass resolution (defined not as line width, but as the separation between the most closely resolved masses).

Using a label-free mass spectrometric approach, we investigated light-induced changes in the distribution of phosphorylated and nitrated proteins within subpopulations of native photosynthetic complexes in the thylakoid membrane of Arabidopsis thaliana leaves adapted to growth light (GL) and subsequently exposed to high light (HL). Eight protein phosphorylation sites were identified in photosystem II (PSII) and the phosphorylation level of seven was regulated by HL as determined based on peak areas from ion chromatograms of phosphorylated and non-phosphorylated peptides. Although the phosphorylation of PSII proteins was reported in the past, we demonstrated for the first time that two minor antenna LHCB4 isoforms are alternately phosphorylated under GL and HL conditions in PSII monomers, dimers and supercomplexes. A role of LHCB4 phosphorylation in state transition and monomerization of PSII under HL conditions is proposed. We determined changes in the nitration level of 23 tyrosine residues in five photosystem I (PSI) and nine PSII proteins and demonstrated for the majority of them a lower nitration level in PSI and PSII complexes and supercomplexes under HL conditions, as compared to GL. In contrast, the nitration level significantly increased in assembled/disassembled PSI and PSII subcomplexes under HL conditions. A possible role of nitration in (1) monomerization of LHCB1-3 trimers under HL conditions (2) binding properties of ferredoxin-NADP+ oxidoreductase to photosystem I, and (3) PSII photodamage and repair cycle, is discussed. Based on these data, we propose that the conversely regulated phosphorylation and nitration levels regulate the stability and turnover of photosynthetic complexes under HL conditions.

A new instrument configuration based on a Finnigan FTMS-2000 platform has been applied to the study of surface-induced dissociation (SID) in this research. Benzene monomer ions C(6)H(6)(+) and dimer ions (C(6)H(6))(2)(+) were impacted on a fluorinated self-assembled monolayer surface at collision energies ranging from 1 to 70 eV. Benzene cations were chosen for this study because the fragmentation characteristics of the molecular cation are well known and its SID has been thoroughly investigated. SID spectra obtained by FTMS-SID are very similar to those reported in the literature for the same surface but exhibit much higher mass resolution. A comparison study of collision-induced dissociation (CID) and SID of benzene molecular cations was performed utilizing the same ICR cell and ion detection protocol. It is demonstrated that SID provides both much higher energy deposition and a narrower internal energy distribution than CID. The present instrument geometry and experimental protocol demonstrate much higher efficiencies than previous SID studies by FTMS and much higher mass resolution than previous SID studies using other types of mass analyzers.

Many factors shift the cyclotron frequency of ions trapped in a Fourier transform ion cyclotron resonance (FT-ICR) trap. The major factors are radial components of the trapping electric field, ion axial displacements from the center of the trap, space charge density, and relativistic mass increase. It is shown that the ion post-excitation radius is the most crucial factor that influences the cyclotron frequency. For an elongated cyclindrical FT-ICR trap, the analytical expressions of the cyclotron frequency shifts for the various factors are derived. They are useful for precise mass measurements carried out on an FT-ICR mass spectrometer.

Information about peptides and proteins in urine can be used to search for biomarkers of early stages of various diseases. The main technology currently used for identification of peptides and proteins is tandem mass spectrometry, in which peptides are identified by mass spectra of their fragmentation products. However, the presence of the fragmentation stage decreases sensitivity of analysis and increases its duration. We have developed a method for identification of human urinary proteins and peptides. This method based on the accurate mass and time tag (AMT) method does not use tandem mass spectrometry. The database of AMT tags containing more than 1381 AMT tags of peptides has been constructed. The software for database filling with AMT tags, normalizing the chromatograms, database application for identification of proteins and peptides, and their quantitative estimation has been developed. The new procedures for peptide identification by tandem mass spectra and the AMT tag database are proposed. The paper also lists novel proteins that have been identified in human urine for the first time.

The kinetics fo production of proton-bound dimers of dimethyl- and diisopropyl-tartrate were analyzed were analyzed by the method of initial slopes. From the pressure dependence of the apparent bimolecular rate constatn, the back-dissociation rate and radiative stabilization of the intermediate excited collision complex was calculated. The back-dissociation (10.3 and 2.8 × 10 3s−1) and radiative (8.2 and 7.1 s−1) rates are compared to literature values for functionally similar acetone. In contrast to acetone these dimers exhibit a back-dissociation reaction to regenerate the monomer species. These results can be taken to imply a lower binding energy in these dimers due to steric effects. Competing reactions to form ions of m/z 145 and 235 were also observed for the dimethyl and diisopropyl ester, respectively.

Generation of a complex proteome database requires use of powerful analytical methods capable of following rapid changes in the proteome due to changing physiological and pathological states of the organism under study. One of the promising technologies with this regard is the use of so-called Accurate Mass and Time (AMT) tag peptide databases. Generation of an AMT database for a complex proteome requires combined efforts by many research groups and laboratories, but the chromatography data resulting from these efforts are tied to the particular experimental conditions and, in general, are not transferable from one platform to another. In this work, we consider an approach to solve this problem that is based on the generation of a universal scale for the chromatography data using a multiple-point normalization method. The method follows from the concept of linear correlation between chromatography data obtained over a wide range of separation parameters. The method is further tested for tryptic peptide mixtures with experimental data collected from mutual studies by different independent research groups using different separation protocols and mass spectrometry data processing tools.

The theory of ion motion in field asymmetric ion mobility spectrometry (FAIMS) conditions has been developed on the bases of an effective field approach and applied to cylindrical and spherical geometries of FAIMS analyzers. The resulting analytical formulae relate compensation voltage to ion characteristics such as non-linear ion mobility coefficient, ion mobility and ion mass and charge. They permit taking into account ion inertia at small pressure of a buffer gas and at high ion mass.

The review deals with methods of recording and reproducing information for external computer memory devices in which Langmuir–Blodgett films are used as carriers and also with the physical effects occurring in these films, which may be used in the future for the creation of new superdense optical information carriers. Attention has concentrated on the photochromic reactions in the J-aggregates of Langmuir–Blodgett films, which permit the reversible recording of information. In many cases the preparation of the carrier and the technical characteristics of the corresponding memory devices are described in detail. The review considers the original studies and patents on this topic which have been published during the last 15 years. The bibliography includes 55 references.