First results are reported on the fragmentation of multiply protonated polypeptide ions produced in electrospray ionization mass spectrometry (ESI-MS) with a beam of high-energy cations as a source of activation. The ion beam is generated with a microwave plasma gun installed on a benchtop Q Exactive mass spectrometer. Precursor polypeptide ions are activated when trapped inside the collision cell of the instrument (HCD cell), and product species are detected in the Orbitrap analyzer. Upon exposure to the beam of air plasma cations (∼100 μA, 5 s), model precursor species such as multiply protonated angiotensin I and ubiquitin dissociated across a variety of pathways. Those pathways include the cleavages of C-CO, C-N as well as N-Cα backbone bonds, accordingly manifested as b/y, a, and c/z fragment ion series in tandem mass spectra. The fragmentation pattern observed includes characteristic fragments of collision-induced dissociation (CID) (b/y/a fragments) as well as electron capture/transfer dissociation (ECD, ETD) (c/z fragments), suggesting substantial contribution of both vibrational and electronic excitation in our experiments. Besides backbone cleavages, notable amounts of nondissociated precursor species were observed with reduced net charge, formed via electron or proton transfer between the colliding partners. Peaks corresponding to increased charge states of the precursor ions were also detected, which is the major distinctive feature of ion beam activation.

Here we report on the gas-phase interactions between protonated enantiopure amino acids (l- and d-enantiomers of Met, Phe, and Trp) and chiral target gases [(R)- and (S)-2-butanol, and (S)-1-phenylethanol] in 0.1–10.0 eV low-energy collisions. Two major processes are seen to occur over this collision energy regime, collision-induced dissociation and ion-molecule complex formation. Both processes were found to be independent of the stereo-chemical composition of the interacting ions and targets. These data shed light on the currently debated mechanisms of gas-phase chiral selectivity by demonstrating the inapplicability of the three-point model to these interactions, at least under single collision conditions. Graphical Abstract Electronic supplementary materialThe online version of this article (10.1007/s13361-017-1796-7) contains supplementary material, which is available to authorized users.

The structures of three proton-bound dimers (Met 2 H + , MetTrpH + , and Trp 2 H + ) are investigated in the gas phase with infrared multiple photon disassociation (IRMPD) spectroscopy in combination with quantum chemical calculations. Their IRMPD spectra in the range of 600−1850 cm −1 are obtained experimentally using an FT-ICR mass spectrometer and the CLIO free electron laser as an IR light source. The most abundant conformers are elucidated by comparing the IRMPD spectra with harmonic frequencies obtained at the B3LYP-GD3BJ/6-311++G** level of theory. Discrepancies between the experimental and theoretical data in the region of 1500−1700 cm −1 are attributed to the anharmonicity of the amino bending modes. We confirm the result of a previous IRMPD study that the structure of gas-phase Trp 2 H + is charge-solvated but find that there are more stable structures than originally reported (Feng, R.; Yin, H.; Kong, X. Rapid Commun. Mass Spectrom. 2016, 30, 24−28). In addition, gas-phase Met 2 H + and MetTrpH + have been revealed to have charge-solvated structures. For all three dimers, the most stable conformer is found to be of type A. The spectrum of Met 2 H + , however, cannot be explained without some abundance of type B charge-solvated conformers as well as salt-bridged structures.

In this work we report the stereo-dependent collision-induced dissociation (CID) of proton-bound complexes of tryptophan and 2-butanol. The dissociation efficiency was measured as a function of collision energy in single collision mode. The homochiral complex was found to be less stable against CID than a heterochiral one. Additional gas dependence measurements were performed with diastereomeric complexes that confirm the findings. KEYWORDSamino acids, chiral recognition, collision induced dissociation, gas phase, mass spectrometry | INTRODUCTIONMass spectrometry (MS) is essentially an achiral method and cannot, in its baseline configuration, discriminate between enantiomers because they have the same mass and fragmentation pattern. This limitation can be overcome by placing the sample in a chiral environment, as first demonstrated by Fales and Wright, 1 and later refined by Tao and Cooks and other groups. 2 The developmental history of MS as a modern, cutting-edge tool in chiral analysis is comprehensively described in a number of recent reviews. [3][4][5] MS-based gas-phase experiments allow studies of the interaction of isolated molecules and ion-molecule pairs in order to observe subtle chiral effects without the influence of a solvent. Several of these techniques rely on the differential interaction of enantiomers in diastereomeric complexes. 6-9 Tao and Cooks developed a kinetic method for enantiomeric analysis. 2 In this method, a chiral analyte and a chiral reference compound are complexed with a transition-metal ion. The transition-metal induces sterically dependent multipoint interactions between the analyte and the reference molecules, which results in different free energies for the trimeric cluster ions formed by the enantiomers of the analyte. This small difference can be converted into detectable differences in fragment-ion branching ratios. 10,11 In a recent study, Zehnacker-Rentien and co-workers investigated systems without a transition metal and detected differences in the collision-induced dissociation rates of hetero-and homochiral complexes of camphor and alanine. 12 The observation of a higher fragmentation efficiency for the heterochiral complex, despite it being calculated to be slightly more stable than the homochiral system, was explained by the presence of a second, lower-energy, conformer of the homochiral complex. The chiral effects of molecular and ionic complexes have been widely studied with different theoretical and experimental approaches in gas-phase spectroscopy. 13 The previous chiral recognition experiments were performed in ion trap configurations, with numerous collisions with a target gas over a distribution of kinetic energies. We recently embarked on a program using ion beams and thin targets in order to study chiral interactions in single,