Four decades of joy in mass spectrometry

Tremendous developments in mass spectrometry have taken place in the last 40 years. This holds for both the science and the instrumental revolutions in this field. In chemistry the research was heavily focused on organic molecules that upon electron ionization fragmented via complex mechanistic pathways as shown by isotopic labeling experiments. These studies, including ion structure determinations, were performed with use of double focusing mass spectrometers of both conventional and reversed geometry, and equipped with various types of metastable ion scanning and collision-induced dissociation techniques developed by physical and analytical chemists. Time-resolved mass spectrometry by use of the field ionization kinetics method, developed by physical chemists, was another powerful way to unravel details of unimolecular gas phase ion dissociations. Then the development of new ionization methods, such as desorption chemical ionization, field desorption, and fast atom bombardment permitted not only to analyze unvolatile, thermally labile and higher molecular weight compounds, but also to study their chemical behavior in the gas phase, initially with use of double focusing instruments and later on with multisector and hybrid mass spectrometers. These ionization methods also enabled to study organometallic compounds and increasingly the field of medium-sized to large biomolecules, the latter being exploded in the last decade by the development of electrospray- and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. Another area of research concerned the bimolecular chemistry of organic ions with organic molecules in the gas phase. Initially this was performed with use of among others drift-cell ion cyclotron resonance spectroscopy, that later on was replaced by the developed method of ion trapping and Fourier transform ion cyclotron resonance. Combination of the latter with the afore-mentioned ionization methods has shifted also in this case the research on organic molecules to organometallic/inorganic systems, and predominantly to biomolecules in the last decade. This invited review will describe the research efforts made by the author's group over the last 40 years together with some personal experiences during his career.     

Hybrid quadrupole mass filter∕quadrupole ion trap∕time-of-flight-mass spectrometer for infrared multiple photon dissociation spectroscopy of mass-selected ions

We present a laboratory-constructed mass spectrometer optimized for recording infrared multiple photon dissociation (IRMPD) spectra of mass-selected ions using a benchtop tunable infrared optical parametric oscillator∕amplifier (OPO∕A). The instrument is equipped with two ionization sources, an electrospray ionization source, as well as an electron ionization source for troubleshooting. This hybrid mass spectrometer is composed of a quadrupole mass filter for mass selection, a reduced pressure (～10(-5) Torr) quadrupole ion trap (QIT) for OPO irradiation, and a reflectron time-of-flight drift tube for detecting the remaining precursor and photofragment ions. A helium gas pulse is introduced into the QIT to temporarily increase the pressure and hence enhance the trapping efficiency of axially injected ions. After a brief pump-down delay, the compact ion cloud is subjected to the focused output from the continuous wave OPO. In a recent study, we implemented this setup in the study of protonated tryptophan, TrpH(+), as well as collision-induced dissociation products of this protonated amino acid [W. K. Mino, Jr., K. Gulyuz, D. Wang, C. N. Stedwell, and N. C. Polfer, J. Phys. Chem. Lett. 2, 299 (2011)]. Here, we give a more detailed account on the figures of merit of such IRMPD experiments. The appreciable photodissociation yields in these measurements demonstrate that IRMPD spectroscopy of covalently bound ions can be routinely carried out using benchtop OPO setups.     

Collisional activation of peptide ions in FT-ICR mass spectrometry

In the last decade, the characterization of complex molecules, particularly biomolecules, became a focus of fundamental and applied research in mass spectrometry. Most of these studies utilize tandem mass spectrometry (MS/MS) to obtain structural information for complex molecules. Tandem mass spectrometry (MS/MS) typically involves the mass selection of a primary ion, its activation by collision or photon excitation, unimolecular decay into fragment ions characteristic of the ion structure and its internal excitation, and mass analysis of the fragment ions. Although the fundamental principles of tandem mass spectrometry of relatively small molecules are fairly well-understood, our understanding of the activation and fragmentation of large molecules is much more primitive. For small ions, a single energetic collision is sufficient to dissociate the ion; however, this is not the case for complex molecules. For large ions, two fundamental limits severely constrain fragmentation in tandem mass spectrometry. First, the center-of-mass collision energy-the absolute upper limit of energy transfer in a collision process-decreases with increasing mass of the projectile ion for fixed ion kinetic energy and neutral mass. Secondly, the dramatic increase in density of states with increasing internal degrees of freedom of the ion decreases the rate of dissociation by many orders of magnitude at a given internal energy. Consequently, most practical MS/MS experiments with complex ions involve multiple-collision activation (MCA-CID), multi-photon activation, or surface-induced dissociation (SID). This review is focused on what has been learned in recent research studies concerned with fundamental aspects of MCA-CID and SID of model peptides, with an emphasis on experiments carried out with Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS). These studies provide the first quantitative comparison of gas-phase multiple-collision activation and SID of peptide ions. Combining collisional energy-resolved data with RRKM-based modeling revealed the effect of peptide size and identity on energy transfer in collisions-very important characteristics of ion activation from fundamental and the analytical perspectives. Finally, the combination of FT-ICR with SID was utilized to carry out the first time-resolved experiments that examine the kinetics of peptide fragmentation. This has lead to the discovery that the time-dependence of ion dissociation varies smoothly up to a certain collision energy, and then shifts dramatically to a time-independent, extensive dissociation. This near-instantaneous "shattering" of the ion generates a large number of relatively small fragment ions. Shattering of ions on surfaces opens up a variety of dissociation pathways that are not accessible with multiple-collision and multiphoton excitation.     

High-energy collision induced dissociation fragmentation pathways of peptides, probed using a multiturn tandem time-of-flight mass spectrometer "MULTUM-TOF/TOF"

A new multiturn tandem time-of-flight (TOF) mass spectrometer "MULTUM-TOF/TOF" has been designed and constructed. It consists of a matrix-assisted laser desorption/ionization ion source, a multiturn TOF mass spectrometer, a collision cell, and a quadratic-field ion mirror. The multiturn TOF mass spectrometer can overcome the problem of precursor ion selection in TOF, due to insufficient time separation between two adjacent TOF peaks, by increasing the number of cycles. As a result, the total TOF increases with the increase in resolving power. The quadratic-field ion mirror allows temporal focusing for fragment ions with different kinetic energies. Product ion spectra from monoisotopically selected precursor ions of angiotensin I, substance P, and bradykinin have been obtained. The fragment ions observed are mainly the result of high-energy collision induced dissociation.     

Activation of large ions in FT-ICR mass spectrometry

The advent of soft ionization techniques, notably electrospray and laser desorption ionization methods, has enabled the extension of mass spectrometric methods to large molecules and molecular complexes. This both greatly extends the applications of mass spectrometry and makes the activation and dissociation of complex ions an integral part of these applications. This review emphasizes the most promising methods for activation and dissociation of complex ions and presents this discussion in the context of general knowledge of reaction kinetics and dynamics largely established for small ions. We then introduce the characteristic differences associated with the higher number of internal degrees of freedom and high density of states associated with molecular complexity. This is reflected primarily in the kinetics of unimolecular dissociation of complex ions, particularly their slow decay and the higher energy content required to induce decomposition--the kinetic shift (KS). The longer trapping time of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) significantly reduces the KS, which presents several advantages over other methods for the investigation of dissociation of complex molecules. After discussing general principles of reaction dynamics related to collisional activation of ions, we describe conventional ways to achieve single- and multiple-collision activation in FT-ICR MS. Sustained off-resonance irradiation (SORI)--the simplest and most robust means of introducing the multiple collision activation process--is discussed in greatest detail. Details of implementation of this technique, required control of experimental parameters, limitations, and examples of very successful application of SORI-CID are described. The advantages of high mass resolving power and the ability to carry out several stages of mass selection and activation intrinsic to FT-ICR MS are demonstrated in several examples. Photodissociation of ions from small molecules can be effected using IR or UV/vis lasers and generally requires tuning lasers to specific wavelengths and/or utilizing high flux, multiphoton excitation to match energy levels in the ion. Photodissociation of complex ions is much easier to accomplish from the basic physics perspective. The quasi-continuum of vibrational states at room temperature makes it very easy to pump relatively large amounts of energy into complex ions and infrared multiphoton dissociation (IRMPD) is a powerful technique for characterizing large ions, particularly biologically relevant molecules. Since both SORI-CID and IRMPD are slow activation methods they have many common characteristics. They are also distinctly different because SORI-CID is intrinsically selective (only ions that have a cyclotron frequency close to the frequency of the excitation field are excited), whereas IRMPD is not (all ions that reside on the optical path of the laser are excited). There are advantages and disadvantages to each technique and in many applications they complement each other. In contrast with these slow activation methods, the less widely appreciated activation method of surface induced dissociation (SID) appears to offer unique advantages because excitation in SID occurs on a sub-picosecond time scale, instantaneously relative to the observation time of any mass spectrometer. Internal energy deposition is quite efficient and readily adjusted by altering the kinetic energy of the impacting ion. The shattering transition--instantaneous decomposition of the ion on the surface--observed at high collision energies enables access to dissociation channels that are not accessible using SORI-CID or IRMPD. Finally, we discuss some approaches for tailoring the surface to achieve particular aims in SID.     

新型电子电离源线型离子阱-飞行时间杂化串联质谱研究进展

本研究介绍了一种新型电子电离源线型离子阱-飞行时间杂化串联质谱仪,该仪器结合了线型离子阱质谱和飞行时间质谱的优点,具有较强的定性分析能力。选用全氟三丁胺(PFTBA)、四氯化碳和丙酮为测试样品对开发的仪器样机进行性能测试,包括对PFTBA碎片离子的离子分离（ISO）和碰撞诱导解离（CID）实验,以及样品同位素离子间的分离实验。测试结果表明,该仪器基本实现了离子碎裂、离子储存和串联质谱分析等功能,能够进行高精度母离子选择。本研究所开发的EI LIT-TOF质谱,在易挥发类有机化合物的结构和化学性质等研究中具有特殊的应用前景。     

拟除虫菊酯类农药在NCI源和EI源中的质谱行为

通过分析19种拟除虫菊酯类农药（pyrethroid pesticides, PyPs）在负化学离子源（NCI）和电子轰击离子源（EI）中的碎片离子信息，得出每种农药在不同离子源中的质谱行为差异。在NCI源中，PyPs获得1个热电子，形成负离子后不稳定而发生热裂解，与酯基相连的碳氧键断裂形成菊酯烷酸根离子，再脱去中性分子（如CO₂、HF、HCl、HCF3等）形成各种碎片离子。一般情况下，含卤原子越多的PyPs，其在NCI源的响应越高。在EI源中，PyPs裂解规律为：1） 与羰基相连的碳氧键发生α-断裂脱去1分子CO，得到含环丙烷结构的特征碎片离子；2） 发生六元环的氢原子重排，当含有苄基苯基醚且甲基上有氰基取代基的PyPs，易形成m/z 181、208特征碎片离子，而不含氰基的PyPs易形成m/z 183特征碎片离子。     

直接输注电喷雾电离四极杆飞行时间质谱在十六种中药来源化合物定性分析中的应用(英文)

采用直接输注电喷雾电离质谱对十六种中药来源的化合物进行了分析。观察了它们的电喷雾电离质谱和串联质谱特征 ,以了解不同结构化合物的电离能力和裂解特点。观察表明 :为使样品成分尽可能多地被检测 ,必须同时进行正负两种模式的分析。化合物结构中羰基的存在似有利于化合物在正离子模式下形成准分子离子或其它分子加和离子。当采样锥电压为 3 0 V时 ,大多数化合物能形成准分子离子或其它分子加和离子。但改变采样锥电压似不能完全避免源内裂解。建议分析时同时考察不同采样锥电压 (如 1 0 V、3 0 V和 5 0 V)。串联质谱分析被证明是获得进一步结构信息的有效手段 ,因为对于所有被观察的准分子离子和其它分子加和离子 ,均能在串联质谱分析中检测到碎片离子。本研究在四物汤的研究中已经成功地运用了该方法。此方法有助于中药混合物中样品成分的快速定性分析     

串联质谱肽段断裂新技术——电子转移解离及其在蛋白质组学中的应用

电子转移解离(ETD) 作为一种新型的肽段序列测定技术,克服了电子捕获解离技术(ECD)中热电子传递和转移时间长的缺点。双离子源技术将供电子的蒽阴离子引入反应体系,直接快速地完成电子转移等一系列反应步骤,同时保留了ECD不断裂微弱的翻译后修饰化学键,得到近乎完全的包含了翻译后各种修饰的肽段序列信息的优势。电子转移解离技术能够分析相对分子质量较大的非酶切肽段,这对于Top-down技术和含有翻译后修饰的大相对分子质量肽段的鉴定具有重要意义。     

Mass filter and focusing ion detector for use with time-of-flight velocity distribution measurements

A novel mass filter and focusing ion detector for time-of-flight studies of dissociative ionization fragments is described. The filter-dector combination is particularly suited for measuring the kinetic energy released in the molecular dissociation process. The mass filter utilizes a computer-controlled, time-dependent retarding potential synchronized with, and located a distance L from, a pulsed electron-bombardment ion source. Ions arriving at the filter at time t have a kinetic energy of mL(2)/2t(2). The retarding potential varies with time as mL(2)/2et(2), thus deflecting ions with masses less than m. Operation of the filter in a mode which provides unity mass resolution at 16 amu has been demonstrated. The detector consists of a channel electron multiplier and a focusing electrode configuration approximating that of a charged sphere above a grounded conducting plane. The planar input aperture of the detector is located just behind the mass filter along the ion flight path. The detector features high efficiency, large input aperture, low background, and simple operation. Ion transit times through the detector are small and essentially independent of the initial ion kinetic energy.     

Mass spectrometric analysis of long-chain lipids

Electrospray and matrix assisted laser desorption ionization generate abundant molecular ion species from all known lipids that have long chain fatty acyl groups esterified or amidated to many different polar headgroup features. Molecular ion species include both positive ions from proton addition [M+H](+) and negative ions from proton abstraction [M-H](-) as well as positive ions from alkali metal attachment and negative ions from acetate or chloride attachment. Collisional activation of both MALDI and ESI behave very similarly in that generated molecular species yield product ions that reveal many structural features of the fatty acyl lipids that can be detected in tandem mass spectrometric experiments. For many lipid species, collision induced dissociation of the positive [M+H](+) reveals information about the polar headgroup, while collision induced dissociation of the negative [M-H](-) provides information about the fatty acyl chain. The mechanisms of formation of many of these lipid product ions have been studied in detail and many established pathways are reviewed here. Specific examples of mass spectrometric behavior of several molecular species are presented, including fatty acids, triacylglycerol, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol, ceramide, and sphingomeylin.     

Mass and lifetime measurements of exotic nuclei in storage rings

Mass and lifetime measurements lead to the discovery and understanding of basic properties of matter. The isotopic nature of the chemical elements, nuclear binding, and the location and strength of nuclear shells are the most outstanding examples leading to the development of the first nuclear models. More recent are the discoveries of new structures of nuclides far from the valley of stability. A new generation of direct mass measurements which allows the exploration of extended areas of the nuclear mass surface with high accuracy has been opened up with the combination of the Experimental Storage Ring ESR and the FRragment Separator FRS at GSI Darmstadt. In-flight separated nuclei are stored in the ring. Their masses are directly determined from the revolution frequency. Dependent on the half-life two complementary methods are applied. Schottky Mass Spectrometry SMS relies on the measurement of the revolution frequency of electron cooled stored ions. The cooling time determines the lower half-life limit to the order of seconds. For Isochronous Mass Spectrometry IMS the ring is operated in an isochronous ion-optical mode. The revolution frequency of the individual ions coasting in the ring is measured using a time-of-flight method. Nuclides with lifetimes down to microseconds become accessible. With SMS masses of several hundreds nuclides have been measured simultaneously with an accuracy in the 2 x 10(-7)-range. This high accuracy and the ability to study large areas of the mass surface are ideal tools to discover new nuclear structure properties and to guide improvements for theoretical mass models. In addition, nuclear half-lives of stored bare and highly charged ions have been measured. This new experimental development is a significant progress since nuclear decay characteristics are mostly known for neutral atoms. For bare and highly charged ions new nuclear decay modes become possible, such as bound-state beta decay. Dramatic changes in the nuclear lifetime have been observed in highly charged ions compared to neutral atoms due to blocking of nuclear decay channels caused by the modified atomic interaction. High ionization degrees prevail in hot stellar matter and thus these experiments have great relevance for the understanding of the synthesis of elements in the universe and astrophysical scenarios in general.     

Threshold photoionization in time-of-flight mass spectrometry

Multi-photon excitation in a time-of-flight mass spectrometer (TOF-MS) is shown to lead to threshold ions with defined internal energy. A powerful technique for the production of threshold ions is based on the excitation of high long-lived Rydberg states embedded in the ionization continuum. The Rydberg molecules are separated with suitable separation techniques from ions produced by a direct multi-photon ionization process. Finally, the ionization of the Rydberg molecules in a delayed pulsed electric field leads to threshold ions. This work reviews several separation techniques, and reports on applications of threshold ionization for investigation of the structure, energetics, and dynamics of neutral molecules, molecular cations, and cluster cations.     

Development of a low-temperature photoelectron spectroscopy instrument using an electrospray ion source and a cryogenically controlled ion trap

The ability to control ion temperatures is critical for gas phase spectroscopy and has been a challenge in chemical physics. A low-temperature photoelectron spectroscopy instrument has been developed for the investigation of complex anions in the gas phase, including multiply charged anions, solvated species, and biological molecules. The new apparatus consists of an electrospray ionization source, a three dimensional (3D) Paul trap for ion accumulation and cooling, a time-of-flight mass spectrometer, and a magnetic-bottle photoelectron analyzer. A key feature of the new instrument is the capability to cool and tune ion temperatures from 10 to 350 K in the 3D Paul trap, which is attached to the cold head of a closed cycle helium refrigerator. Ion cooling is accomplished in the Paul trap via collisions with a background gas and has been demonstrated by observation of complete elimination of vibrational hot bands in photoelectron spectra of various anions ranging from small molecules to complex species. Further evidence of ion cooling is shown by the observation of H2-physisorbed anions at low temperatures. Cold anions result in better resolved photoelectron spectra due to the elimination of vibrational hot bands and yield more accurate energetic and spectroscopic information. Temperature-dependent studies are made possible for weakly bonded molecular and solvated clusters, allowing thermodynamic information to be obtained.     

Structures,energetics, and dynamics of gas phase ions studied by FTICR and HPMS

Both Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS) and high‐pressure mass spectrometry (HPMS) are very powerful tools in the field of gas phase ion chemistry. Many experimental method developments based on FTICR‐MS and HPMS are summarized, including the coupling of a high‐pressure external ion source to a FTICR mass spectrometer, blackbody infrared radiative dissociation (BIRD), coupling laser desorption ionization with HPMS, infrared multiple photon dissociation (IRMPD), radiative association and bimolecular routes to gas phase cluster ion formation. An abundance of thermochemical data, such as proton affinities, gas phase acidities, methyl cation affinities and metal cation affinities, have been obtained. Some of these data are the basis of the standard data listed in the NIST thermochemical databases. Ion–molecule interactions, energetics, reactivities, and structures of molecules have been extensively investigated using the methods developed based on HPMS and FTICR mass spectrometric techniques. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:546–585, 2009     

Reactions of polypeptide ions with electrons in the gas phase

Reactions of electrons in the energy range below 70 eV with polypeptide cations and anions are reviewed, as well as their applications for the structural analysis of polypeptides. At very low energies (相似文献   

Orthogonal acceleration time-of-flight mass spectrometry

The principles and applications of time-of-flight mass spectrometry involving instruments with independent (orthogonal) axes for ion generation and mass analysis are reviewed. This approach, generally referred to as orthogonal acceleration time-of-flight mass spectrometry, has proved particularly advantageous for the combination of continuous ionization sources with time-of-flight mass spectrometry. The history of the technique is briefly discussed along with the instrumental principles pertaining to all the stages of the instrumentation from ion source to detector. The applications of commercial and customized instruments are discussed for several ionization methods including electrospray, matrix assisted laser desorption/ionization, electron ionization, and plasma ionization.     

Infrared spectroscopy of organometallic ions in the gas phase: from model to real world complexes

Gas phase mid-infrared spectroscopy of molecular ions can nowadays be performed with high performance mass spectrometers coupled to free electron lasers (FEL). The wide and continuous tunability of highly intense FELs in the mid-infrared region can be exploited for performing infrared multiple photon dissociation (IRMPD) spectroscopy of molecular ions. This review will focus on gas phase IRMPD spectroscopic investigations aiming at probing the structure and the reactivity of transition metal complexes. The performance of infrared spectroscopy for characterizing the coordination mode of polydentate ligands and the spin state of the metal will be illustrated. Infrared spectroscopy has also been exploited to probe the reactivity of metal complexes, and a special attention will be given to the infrared spectroscopy of reactive intermediates.     

Recent developments in the ion/ion chemistry of high-mass multiply charged ions

The ability to form multiply charged high-mass ions in the gas-phase, most notably via electrospray ionization (ESI), has allowed the study of many different combinations of positively and negatively charged ions. The charged products are directly amenable to study with mass spectrometry. Ion/ion reactions have proved to be "universal" in the sense that the high exothermicities and large rate constants associated with essentially any combination of oppositely charged ions lead to reaction regardless of the chemical functionalities associated with the ions. These characteristics make ion/ion reactions potentially analytically useful provided reagent ion densities and spatial overlap of the oppositely charged ions are high. These conditions can be readily met by several instrumental configurations. The focus of this review is to highlight developments in this field since 1998. Novel instrumentation has been developed to study ion/ion reactions, such as atmospheric pressure ion/ion reactors followed by mass analysis, or electrodynamic ion trap mass spectrometers, which are used as reaction vessels at sub-atmospheric pressures. A wide variety of reaction phenomenologies have been observed in various ion/ion reactions, with proton transfer being the most common. New phenomenologies have been observed in the reactions of multiply charged positive ions with singly charged negative ions, including cation transfer and cation exchange. A new series of reactions between multiply charged positive ions and multiply charged negative ions have been made possible by recent instrumentation developments. These reactions have led to the observation of proton transfer and complex formation. These observations have provided new insights into ion/ion reaction dynamics and a bound orbit model appears to best account for experimental results. New applications are also discussed for a several ion/ion reaction.     

Detection and speciation of brominated flame retardants in high-impact polystyrene (HIPS) polymers

Polymeric materials have been suggested as possible environmental sources of persistent organic pollutants such as flame retardants. In situ, micrometre-scale characterization techniques for polymer matrix containing flame retardants may provide some insight into the dominant environmental transfer mechanism(s) of these brominated compounds. In this work, we demonstrate that micro X-ray fluorescence spectroscopy (μXRF), focused ion beam scanning electron microscopy (FIB-SEM) combined with energy dispersive X-ray spectroscopy (EDS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) are promising techniques for the elemental and chemical identification of brominated fire retardant compounds (such as the deca-congener of polybrominated diphenyl ether, BDE-209) within polymeric materials (e.g. high-impact polystyrene or HIPS). Data from μXRF demonstrated that bromine (Br) inclusions were evenly distributed throughout the HIPS samples, whereas FIB SEM-EDS analysis revealed that small antimony (Sb) and Br inclusions are present, and regionally higher concentrations of Br surround the Sb inclusions (compared to the bulk material). Four prominent mass-to-charge ratio peaks (m/z 485, 487, 489 and 491) that correspond to BDE-209 were identified by ToF-SIMS and can be used to chemically distinguish this molecule on the surface of polymeric materials with respect to other brominated organic molecules. These techniques can be important in any study that investigates the route of entry to the environmental surroundings of BDE-containing materials.