Marcos N. Eberlin

Ambient mass spectrometry: bringing MS into the "real world".

AbstractMass spectrometry has recently undergone a second contemporary revolution with the introduction of a new group of desorption/ionization (DI) techniques known collectively as ambient mass spectrometry. Performed in an open atmosphere directly on samples in their natural environments or matrices, or by using auxiliary surfaces, ambient mass spectrometry (MS) has greatly simplified and increased the speed of MS analysis. Since its debut in 2004 there has been explosive growth in the applications and variants of ambient MS, and a very comprehensive set of techniques based on different desorption and ionization mechanisms is now available. Most types of molecules with a large range of masses and polarities can be ionized with great ease and simplicity with the outstanding combination of the speed, selectivity, and sensitivity of MS detection. This review describes and compares the basis of ionization and the concepts of the most promising ambient MS techniques known to date and illustrates, via typical analytical and bioanalytical applications, how ambient MS is helping to bring MS analysis deeper than ever into the “real world” open atmosphere environment—to wherever MS is needed. FigureSchematic of EASI

Phenolic Antioxidants Identified by ESI-MS from Yerba Maté (Ilex paraguariensis) and Green Tea (Camelia sinensis) Extracts

Aqueous extracts of green yerba maté (Ilex paraguariensis) and green tea (Camellia sinensis) are good sources of phenolic antioxidants, as already described in the literature. The subject of this study were organic extracts from yerba maté, both green and roasted, and from green tea. Their phenolic profiles were characterized by direct infusion electrospray insertion mass spectrometry (ESI-MS) and their free radical scavenging activity was determined by the DPPH assay. Organic extracts containing phenolic antioxidants might be used as natural antioxidants by the food industry, replacing the synthetic phenolic additives used nowadays. Ethanolic and aqueous extracts from green yerba maté, roasted yerba maté and green tea showed excellent DPPH scavenging activity (>89%). The ether extracts from green and roasted yerba maté displayed a weak scavenging activity, different from the behavior observed for the green tea ether extract. The main phenolic compounds identified in green yerba maté water and ethanolic extracts were: caffeic acid, quinic acid, caffeoyl glucose, caffeoylquinic acid, feruloylquinic acid, dicaffeoylquinic acid and rutin. After the roasting process two new compounds were formed: caffeoylshikimic acid and dicaffeoylshikimic acid. The ethanolic extracts from yerba maté, both roasted and green, with lower content of phenolic compounds (3.80 and 2.83 mg/mL) presented high antioxidant activity and even at very low phenolic concentrations, ether extract from GT (0.07 mg/mL) inhibited DPPH over 90%.

Easy ambient sonic-spray ionization-membrane interface mass spectrometry for direct analysis of solution constituents.

Using a cellulose dialysis membrane and aqueous solutions of common drugs as a proof-of-principle example, we demonstrate that solid but permeable and flexible membranes can be used as interfaces for the direct analysis of solution constituents via easy ambient sonic-spray ionization mass spectrometry. This new combination of MS techniques, herein termed EASI-MIMS, promotes droplet pick up of the analyte from the external surface of the membrane from where the analyte has selectively permeated for proper mass spectrometry characterization and quantitation. Possible application of EASI-MIMS such as the environmental analyses of effluents, on-line monitoring of fermentation and biotransformations and on-line pharmacokinetic blood analysis are discussed.

Electrospray Ionization Mass Spectrometry: A Major Tool to Investigate Reaction Mechanisms in Both Solution and the Gas Phase:

Electrospray ionization mass spectrometry (ESI-MS), in conjunction with its tandem version ESI-MS/MS, is now established as a major tool to study reaction mechanisms in solution. This suitability results mainly from the ability of ESI to “fish” ions directly from solution to the gas phase environment of mass spectrometers. In this review, we summarize recent studies from our laboratory on the use of on-line monitoring by ESI-MS ion fishing of several types of reactions that permitted us to follow how these reactions progress as a function of both time and conditions using the ultra-high sensitivity and speed of ESI-MS to detect and even characterize transient reaction intermediates. We also show that the intrinsic reactivity of each key gaseous species fished by ESI can be further investigated via ESI-tandem mass spectrometry experiments, searching for the most active species via gas-phase ion/molecule reactions. In the gas-phase, solvent and counter-ion effects are absent. These studies often permit a detailed overview of major steps via the interception, characterization and reactivity investigation of key reaction players.

Easy Ambient Sonic-Spray Ionization Mass Spectrometry Combined with Thin-Layer Chromatography

On-spot detection and analyte characterization on thin-layer chromatography (TLC) plates is performed via ambient desorption/ionization and (tandem) mass spectrometry detection, that is, via easy ambient sonic spray ionization mass spectrometry (EASI-MS). As proof-of-principle cases, mixtures of semipolar nitrogenated compounds as well as pharmaceutical drugs and vegetable oils have been tested. The technique has also been applied to monitor a chemical reaction of synthetic importance. EASI is the simplest and gentlest ambient ionization technique currently available, assisted solely by N2 (or air). It uses no voltages, no electrical discharges; no UV or laser beams, and no high temperature and is most easily implemented in all API mass spectrometers. TLC is also the simplest, fastest, and most easily performed chromatographic technique. TLC plus EASI-MS therefore provide a simple and advantageous combination of chromatographic separation and sensitive detection of the TLC spots as well as on-spot MS or MS/MS characterization. The favorable characteristics of TLC-EASI-MS indicate advantageous applications in several areas such as drug and oil analysis, phytochemistry and synthetic chemistry, forensics via reliable counterfeit detection, and quality control.

Oil Wastes as Unconventional Substrates for Rhamnolipid Biosurfactant Production by Pseudomonas aeruginosa LBI

Oil wastes were evaluated as alternative low‐cost substrates for the production of rhamnolipids by Pseudomonas aeruginosa LBI strain. Wastes obtained from soybean, cottonseed, babassu, palm, and corn oil refinery were tested. The soybean soapstock waste was the best substrate, generating 11.7 g/L of rhamnolipids with a surface tension of 26.9 mN/m, a critical micelle concentration of 51.5 mg/L, and a production yield of 75%. The monorhamnolipid RhaC10C10 predominates when P. aeruginosa LBI was cultivated on hydrophobic substrates, whereas hydrophilic carbon sources form the dirhamnolipid Rha2C10C10 predominantly.

Definitions of terms relating to mass spectrometry (IUPAC Recommendations 2013)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.

Synthesis and Characterization of a Metal Complex Containing Naringin and Cu, and its Antioxidant, Antimicrobial, Antiinflammatory and Tumor Cell Cytotoxicity

The antioxidant activity of flavonoids is believed to increase when they are coordinated with transition metal ions. However, the literature on this subject is contradictory and the outcome seems to largely depend on the experimental conditions. In order to understand the contribution of the metal coordination and the type of interaction between a flavonoid and the metal ion, in this study a new metal complex of Cu (II) with naringin was synthesized and characterized by FT-IR, UV-VIS, mass spectrometry (ESI-MS/MS), elemental analysis and 1H-NMR. The results of these analyses indicate that the complex has a Cu (II) ion coordinated via positions 4 and 5 of the flavonoid. The antioxidant, anti-inflammatory and antimicrobial activities of this complex were studied and compared with the activity of free naringin. The Naringin-Cu (II) complex 1 showed higher antioxidant, anti-inflammatory and tumor cell cytotoxicity activities than free naringin without reducing cell viability.

Venturi Easy Ambient Sonic-Spray Ionization

The development and illustrative applications of an ambient ionization technique termed Venturi easy ambient sonic-spray ionization (V-EASI) is described. Its dual mode of operation with Venturi self-pumping makes V-EASI applicable to the direct mass spectrometric analysis of both liquid (V(L)-EASI) and solid (V(S)-EASI) samples. V-EASI is simple and easy to assemble, operating solely via the assistance of a sonic stream of nitrogen or air. The sonic gas stream causes two beneficial and integrated effects: (a) the self-pumping of solutions via the Venturi effect and (b) sonic-spray ionization (SSI) of analytes either in solution or resting on solid surfaces. In its liquid mode, V(L)-EASI is applicable to analytes in solution, forming negatively and/or positively charged intact molecular species in a soft fashion with little or no fragmentation. In its solid mode, V(S)-EASI relies on Venturi self-pumping of a proper SSI solvent solution in combination with SSI to form a stream of bipolar charged droplets that bombard the sample surface, causing desorption and ionization of the analyte molecules. As for its precursor technique (EASI), V-EASI generates bipolar droplets with considerably lower average charging, which increases selectivity for ionization with high signal-to-noise ratios and clean spectra dominated by single molecular species with minimal solvent ions. V-EASI also operates in a voltage-, heat-, and radiation-free fashion and is therefore free of thermal, electrical, or discharge interferences.

The Bridge Connecting Gas‐Phase and Solution Chemistries

Mass spectrometry (MS) has long served as the gas-phase nursery for exotic ions of ephemeral existence and reactions of ephemeral occurrence in solution. These examples include CH5 , the first ever pentavalent form of carbon, which was later formed in a superacid solution by Olah and Schlosberg; and many elusive ionized molecules such as the prototype carbonyl ylide in its “excentric” distonic ion form, CH2 O CH2, with an apparently bizarre separation of charge and spin sites. MS has also served as the gas-phase medium in which to form key ions and hence probe reaction mechanisms and establish intrinsic reactivity orders. Gaseous NO2 , for instance, was used to settle the mechanism of electrophilic aromatic nitration, a chemical canon that was enthusiastically debated over for decades. Intrinsic physicochemical properties and catalysis, most particularly directed to the activation of inert C H bonds, have also been extensively investigated in gas-phase reactions of (organo)metallic ions. MS was born, however, with a “genetic defect”, that is, “blindness” to neutral species. But an elegant strategy was elaborated, and distant charge sites (negative or positive) were used as charged tags to allow MS to manipulate otherwise neutral species such as radicals. However, skepticism obscured the beauty of gas-phase ion chemistry because the high vacuum was considered by many as an eccentric environment with no bridge to the “real world” of solutions. But John Fenn came to the rescue with his Nobel Prize winning electrospray ionization (ESI) technique. To paraphrase Fenn: “ESI made the power and elegance of MS applicable to both gas-phase and solution ions”. ESI was revolutionary since it brought MS down to the “real world” of solutions by “fishing” solution ions directly into the gas phase. ESI-MS provides continuous snapshots of the dynamic ionic composition of reaction solutions, and ESI-MS “ion fishing” investigations of reaction mechanisms are therefore free from the gas-phase skepticism; the MS bridge is still being used since ions are transferred to the gas phase for MS analysis but they are fished from the reaction medium exactly at the moment of action, and stay mostly undisturbed in the gas phase during their flight to the MS detector. But ESI is also blind to neutral species. To again overcome this limitation, the elegant concept of charged tags developed in the gas phase was brought into solution to facilitate the “flight to the moon”, as Scheme 1 exemplifies. In his Nobel lecture, Fenn summarized ESI as “wings for molecular elephants”; similarly, the combination of ESI and charged tags can be viewed as “charged wings for the flying fish of reaction intermediates” (Figure 1). The gas phase continued to play a major role since the gaseous intermediates can still be investigated by MS to access intrinsic reactivities and functions in the specific reaction step they were fished from. ESI has also allowed