Optical spectroscopy coupled with mass spectrometry methods

Mass spectrometry (MS) is a widely used technique for molecular characterization. It finds applications in various fields of chemistry such as trace analysis, in which it is often coupled with separation methods. Methods relying on mass-to-charge ratio measurements are also a unique tool for accessing the spectroscopy of ionic species. The first studies were devoted to relatively small species, which can be easily put into the gas phase. Among others, tandem mass spectrometry approaches have allowed the study of a wealth of model clusters of fundamental importance in the fields of astrophysics and solvation;^1,2 methods involving photo ionisation have allowed highly-resolved spectra to be obtained for aromatic cations,³ while photo-detachment experiments have been used for studying anionic clusters.⁴ A few spectroscopic studies of neutral systems that rely on their ionisation are reported in this themed issue, such as valence and core photoelectron spectroscopy of biomolecules by Speranza et al. (DOI: 10.1039/C5CP01471A), the photodissociation of ethanethiol leading to SH bond fission as studied by velocity-map imaging by Fárnik (DOI: 10.1039/C5CP00367A), or the dynamics of excimer formation in the benzene dimer probed by ps pump probe experiments reported by Miyazaki and Fujii (DOI: 10.1039/C5CP03010B). Mass spectrometry has evolved considerably with the discovery of soft ionization techniques such as electrospray ionization (ESI)⁵ and matrix-assisted laser desorption/ionisation (MALDI)⁶ coupled with ion traps, which allow ionic species to be stored for a long period of time. As a result, MS is nowadays a major analytical tool for determining the structure of biomolecules put intact in the gas phase. Indeed, the charged species are trapped long enough to undergo the desired reaction or process, without being influenced by the environment. Moreover, isolated species often reproduce what happens in the entire biomolecule better than its isolated fragment in solution. The experiments often resort to multi-stage mass spectrometry coupled with different activation methods, such as collision-induced dissociation (CID), ion–molecule reactions, or electron capture and transfer dissociation (ECD/ETD).⁷ These methods, together with others such as deuterium exchange, allow complex systems to be studied, including reaction intermediates and biomolecular structures. The results, however, are not unambiguous in terms of structure determination, even when the introduction of an ion mobility stage allows for the separation of isomers on the basis of their mobility prior to ion storage. For example, structural information is difficult to obtain for sugars due to multiple stereoisomers, systems showing post-translational modifications are fragile, etc. Additional techniques are therefore highly desirable. Coupling of ion traps with optical methods is a powerful tool for characterizing molecular ions. It has spread only recently though its feasibility was demonstrated first in the 80’s, with fragmentation triggered by a CO₂ laser.⁸ The experiments obtained in the IR range by coupling a free-electron laser (FEL) to a mass spectrometer⁹ have been followed by abundant work in the IR and the UV range. The second revolution in the field is due to the development of cryogenic ion traps, which has opened up the way to a wealth of new approaches for ion spectroscopy.¹⁰

This special issue aims at giving a flavour of the recent development of mass spectrometry coupled with optical spectroscopy. Due to the low density of species in ion traps or guides, all the methods described here rely on action spectroscopy. Most of the time, the absorption of a photon manifests itself by the dissociation of a molecular ion or the fragmentation of a complex. Dissociation can be triggered by a single photon absorption and might require the use of a tag, when the dissociation energy is above that of the photon. This is often the case in tandem mass spectrometers coupled with a supersonic expansion because the formed ions are cold. This sort of study encompass model systems which illustrate the role of protonation on conformational locking by Dopfer, Crestoni and coworkers (DOI: 10.1039/C5CP00221D) or a comparison of diastereomerism effects in neutral, radical cations, and protonated species by Dopfer and Zehnacker (DOI: 10.1039/C5CP00576K).

Ions trapped at room temperature are more easily dissociated, especially when multiple photons are absorbed, as in infra-red resonant multiple photon dissociation (IRMPD) experiments. However, few articles have focused so far on the multiple photon absorption process itself, although it is highly non-linear. Calvo et al. (DOI: 10.1039/C5CP02304A) report a theoretical approach on the influence of the experimental irradiation conditions (laser intensity, spectral with and irradiation time) on the non-linearity of the process, with consequences for the intensities and spectral broadening. Also UV photo dissociation may involve the absorption of more than one photon, as discussed in the contribution of Blanksby, Trevitt and coworkers (DOI: 10.1039/C5CP02035B).

The IRMPD experiments described in this issue first aim at answering fundamental chemical issues, such as organometallic catalysis activation of methane by a metal, studied by the group of Metz (DOI: 10.1039/C5CP01757B), and the IRPD of D₂-tagged MOH(H₂O)⁺ in a cryogenic ion trap reported by Garand (DOI: 10.1039/C5CP01522G). This study aims at assessing the amount of charge transfer between a hydroxyl and a transition metal M. Abundant work is devoted to biological questions, such as the interaction between biomolecules like peptides or DNA bases with metals (see Oomens, Armentrout and coworkers DOI: 10.1039/C5CP01500F, or Fridgen DOI: 10.1039/C5CP00580A) or the conformational flexibility of nucleosides by Oomens and Rodgers (DOI: 10.1039/C5CP02227D). IRMPD is an elegant tool for studying species linked to reduction–oxidation of elementary bricks of life. Radicals are formed prior to the spectroscopic stage, either directly from the ESI source or by chemical reaction, as described by Maître, Radom, O’Hair, and coworkers (DOI: 10.1039/C5CP01573A) for the oxidation products of the deoxyguanosine radical cation. ECD is a very elegant and soft method for producing metastable reduced forms of organometallic complexes, the structure of which can be subsequently probed by IRMPD for determining the localisation of the excess electron (see van der Rest, Frison and coworkers DOI: 10.1039/C5CP01501D). The latter paper illustrates how the use of IRMPD as an analytical tool requires specific spectroscopic signatures for biologically-relevant functions. This is fulfilled for reduced or normal forms of a Zinc complex with diazafluorenone ligands, which have very different spectral signatures. The Crestoni group has shown that O-sulfation of amino acids has a very characteristic spectroscopic signature (DOI: 10.1039/C5CP01409C); Scuderi et al. have also spectroscopically differentiated sulfone and sulfoxides in products resulting from the γ irradiation of thioether-containing peptides (DOI: 10.1039/C5CP03223G).

The building of a solvation network around an ion raises questions which IR spectroscopy can help answer. The question of the specificity of spectral signatures of the first and second solvation shell is discussed for the example of a sulfate by Ohanessian (DOI: 10.1039/C5CP02557E). The study by Asuka Fujii et al. (DOI: 10.1039/C5CP01487E) of protonated amine clusters with up to 22 water molecules illustrates the competition between the stability of the water network itself and the formation of a dipole, which is necessary for stabilising the ion. From a theoretical point of view, these clusters are rather challenging. Asmis, Neumark, and coworkers (DOI: 10.1039/C5CP02253C) show that fluctuations of the hydrogen bond network have to be taken into account and temperature effects are important, even at low temperatures. The study of solvation of an ion by water is especially relevant in the field of atmospheric chemistry. The molecular and macroscopic steps merge with the study of aerosols, the study of which requires specific experimental developments described by Signorell (DOI: 10.1039/C5CP00061K) involving a time-of-flight mass spectrometry stage for detection.

Despite its interest, IRMPD encounters several limitations which are currently pushed back. The first one is its lack of conformational selectivity. This can be overcome by measuring the dissociation kinetics, which differ for bands arising from different conformers,¹¹ as described by Maître, Pino and coworkers (DOI: 10.1039/C5CP02221E) for complexes between DNA bases and a metal ion. The addition of an ion mobility stage between the ion production and the mass analyser allows conformers to be separated on the basis of their shape.¹² The second limitation is of a theoretical nature. Due to the floppy nature of the biomolecules, anharmonicity and temperature effects are of prime importance but their treatment for large systems is theoretically challenging. They are especially important for experiments in the far IR domain, as reported by Gaigeot, Rijs and coworkers (DOI: 10.1039/C5CP01518A). Approaches resulting from molecular dynamics at finite temperature and the correlation of dipoles are very useful for reproducing vibrational spectra. This is illustrated by the study by Barnes et al. (DOI: 10.1039/C5CP02079D) on sulfated carbohydrates, for which generalized second-order vibrational perturbation theory satisfactorily reproduces the IR spectrum. Ohanessian, Clavaguéra et al. describe how polarisable force fields allow the exploration of very complex potential energy surfaces and the assignment of vibrational modes of finite temperature IR spectra without Hessian calculation (DOI: 10.1039/C5CP02270C).

UV spectroscopy in an ion trap depends on the UV photo-dissociation (UVPD) of the trapped ions; being an action spectroscopy, it provides both spectroscopic and dynamic information. From a spectroscopic point of view, it provides invaluable data on the nature of the electronic excited state of protonated ions, including systems in which the proton lies on the aromatic ring (see Blanksby, Trevitt and coworkers DOI: 10.1039/C5CP02035B). The possibilities offered by room temperature or variable temperature traps make the study of very large systems relevant for life chemistry, or supramolecular chemistry at a reach. This themed issue describes systems as large as a protonated chromophore caged in a crown ether, for which a nicely resolved electronic spectrum is obtained in cryogenic conditions by Ebata and Jouvet (DOI: 10.1039/C5CP01960E), antitumor drugs by Dugourd, Antoine and coworkers (DOI: 10.1039/C5CP01498K), the Soret absorption band of a tagged-chlorophyll by Nielsen (DOI: 10.1039/C5CP01513H) and the Q band of a heme–Fe(III) complex by Shafizadeh (DOI: 10.1039/C5CP01585E). For the latter, the possibility offered by controlled-temperature traps makes it possible to evidence the heme–Fe(III)–O₂ complex, which was elusive in solution, and to measure its stability. Combined with high-level ab initio calculations, UVPD is in some cases able to give reliable structural information by comparing the electronic spectrum, namely, transition origin and distribution of Franck–Condon factors, to those calculated for each conformer. It allows, for example, the location of the proton to be determined in model systems of biomolecules, the activity of which strongly depends on the charge state and location. This is nicely illustrated by Jouvet (DOI: 10.1039/C5CP01122A) and Dugourd, Antoine and coworkers (DOI: 10.1039/C5CP01498K). Comparison with solution is especially interesting in this respect as gas-phase experiments often stabilise metastable structures different from the native one, so that one can obtain the electronic spectrum of each charge state separately. For molecules which do not fragment easily, a tag or the absorption of a second photon in the excited state may be required. The latter process is elegantly used by Broquier, Soorkia, and Gregoire (DOI: 10.1039/C5CP01375E) for measuring the excited-state lifetime of protonated ions in cryogenic trap conditions by means of pump–probe experiments in the ps range, giving information on the excited-state dynamics of cold protonated tyramine. Coupling with synchrotron radiation has recently extended the reach of UVPD to the far UV, making it possible to measure, over a wide range, the dependence of the fragmentation process upon the photon energy for the protonated substance P and silver hydride nanoclusters, as reported by Giuliani, Nahon and coworkers (DOI: 10.1039/C4CP04762A and DOI: 10.1039/C5CP01160D).

The relation between the gas-phase structure and the solution-phase structure is still a matter of debate. In other words, are the studied species kinetically trapped and retain their most stable solution-phase conformation or do they relax to their most stable gas-phase structure? This question has important consequences for applications in molecular recognition¹³ and for potential energy surface exploration. Indeed, theoretical modeling leads to the most stable gas phase form and the finding of kinetically-trapped species is a real challenge. Different experimental approaches tackle this problem. The studied ions can be activated by collision before injection in the cold ion trap to drive them to kinetic equilibrium (see Rizzo DOI: 10.1039/C5CP01651G). The conformer distribution can also be modified by photoisomerisation, as reported by Bieske (DOI: 10.1039/C5CP01567G).

Several new action spectroscopy methods have been developed in the last few years. Action electronic energy transfer (Action EET), reported by Julian (DOI: 10.1039/C5CP01617G), is related to the well-known Förster resonant energy transfer (FRET) in solution and consists of detecting the specific mass loss resulting from electronic EET from the optically-excited aromatic amino acid to the disulfite bond, thereby probing the distance between them. Photoisomerisation action (PISA) spectroscopy, developed by Bieske and coworkers, rests on the detection of ion mobility changes due to light-induced isomerisation (DOI: 10.1039/C5CP01567G) and is applied to the photochromic protonated spiropyran–merocyanine system. The use of an ion mobility–photoexcitation–ion mobility scheme endows this method with conformer selectivity.

In conclusion, recent and ongoing developments offer promising new possibilities for structural characterisation as well as the study of the photo-stability of charged species. The far IR range has been explored recently, with information on modes delocalised over the whole system or hydrogen bond modes. UV/visible studies now extend to the far UV range. During the last few years, complex coupling schemes between various aspects of mass spectrometry and spectroscopy have been introduced. One can mention the multimodal detection of photo-fragments, ps pump–probe experiments, a tandem ion mobility–photoexcitation–ion mobility scheme, coupling between ion mobility and cryogenic traps, to name but a few. Size selectivity, which is inherent to mass spectrometry, is now accompanied by conformer specificity. Conformer families can be physically separated via ion mobility before being trapped or differentiated by the action process itself, such as conformer-selective UVPD channels or IRMPD kinetics. Unambiguous conformer-selective results are gathered via double resonance experiments, eventually coupled with recently-developed judicious RF sequences which allow fragments due to the pump to be distinguished from those due to the probe. This arsenal of experimental techniques allows results to be gathered with a so far unrivalled precision for molecules of increasing size, which can serve as a guide for calculations. Indeed vibrational spectroscopy data provide information on the hydrogen bond network, while ion mobility describes the global shape and EET imposes distances between chromophores, which can be subsequently used as constraints in the potential energy surface exploration. Lastly, these experiments have prompted the development of adapted theoretical methods, in particular those allowing fast and efficient exploration of complex potential energy surfaces, such as polarisable force fields, and the treatment of anharmonicity.

I would like to thank the PCCP editorial board for offering me the possibility of acting as a guest editor and the PCCP editorial staff for their efficiency. I express my gratitude to the reviewers for their thorough reading and to all the authors for enriching this themed issue with their contributions.

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