Evaluating the Effects of Metal Adduction and Charge Isomerism on Ion-Mobility Measurements using m-Xylene Macrocycles as Models

Abstract

Gas-phase ion-mobility spectrometry provides a unique platform to study the effect of mobile charge(s) or charge location on collisional cross section and ion separation. Here, we evaluate the effects of cation/anion adduction in a series of xylene and pyridyl macrocycles that contain ureas and thioureas. We explore how zinc binding led to unexpected deprotonation of the thiourea macrocyclic host in positive polarity ionization and subsequently how charge isomerism due to cation (zinc metal) and anion (chloride counterion) adduction or proton competition among acceptors can affect the measured collisional cross sections in helium and nitrogen buffer gases. Our approach uses synthetic chemistry to design macrocycle targets and a combination of ion-mobility spectrometry mass spectrometry experiments and quantum mechanics calculations to characterize their structural properties. We demonstrate that charge isomerism significantly improves ion-mobility resolution and allows for determination of the metal binding mechanism in metal–inclusion macrocyclic complexes. Additionally, charge isomers can be populated in molecules where individual protons are shared between acceptors. In these cases, interactions via drift gas collisions magnify the conformational differences. Finally, for the macrocyclic systems we report here, charge isomers are observed in both helium and nitrogen drift gases with similar resolution. The separation factor does not simply increase with increasing drift gas polarizability. Our study sheds light on important properties of charge isomerism and offers strategies to take advantage of this phenomenon in analytical separations.

Adduct Ions as Diagnostic Probes of Metallosupramolecular Complexes Using Ion Mobility Mass Spectrometry

“… 1 These charge-carrying species can also affect intrinsic properties of the sample molecules, as previously reported for a range of compound classes such as carbohydrates, 2 glycans and glycopeptides, 3 steroids, 4 fullerenes, 5 and macrocycles. 5 , 6 For example, Kellner et al showed that the formation, disassembly, and stability of crown ether fullerene dimers depend on the size of the alkali metal cations used, which was attributed to different binding sites. 5 Rister et al used IM-MS to separate isobaric steroids and reported varying CCS resolutions for different A + , highlighting the relevance of choosing the most suitable charge-carrying species for this application.…”

Pseudopeptidic host adaptation in peptide recognition unveiled by ion mobility mass spectrometry

“…However, IMS-MS is still highly underexploited in the field of synthetic cages or macrocycles and their host : guest chemistry. [34][35][36][37][38][39][40][41][42][43] Herein, a combination of MS methods (single-stage, collision induced dissociation (CID) and IMS-MS experiments), fluorescence spectroscopy, NMR as well as molecular modelling of the supramolecular complexes of the Cy cages and the peptide EYE is reported to decipher the intimate details of the binding event, both in aqueous solution and in the gas-phase.…”

Mouse Pancreatic Peptide Hormones Probed at the Sub-Single-Islet Level: The Effects of Acute Corticosterone Treatment

“…We reported the helium CCS to directly compare our results with their data (see also Table S2). The calculations were done using the following linear approximation described by eq CCS normalN 2 = CCS He × 1.091 + 53.9 …”

“…The calculations were done using the following linear approximation described by eq 2. 50 = × + CCS CCS 1.091 53.9…”