Ion Mobility Mass Spectrometry for Large Synthetic Molecules: Expanding the Analytical Toolbox

Abstract

Understanding the composition, structure and stability of larger synthetic molecules is crucial for their design, yet currently the analytical tools commonly used do not always provide this information. In this perspective, we show how ion mobility mass spectrometry (IM-MS), in combination with tandem mass spectrometry, complementary techniques and computational methods, can be used to structurally characterize synthetic molecules, make and predict new complexes, monitor disassembly processes and determine stability. Using IM-MS, we present an experimental and computational framework for the analysis and design of complex molecular architectures such as (metallo)supramolecular cages, nanoclusters, interlocked molecules, rotaxanes, dendrimers, polymers and host−guest complexes.

Modern Electrospray Ionization Mass Spectrometry Techniques for the Characterization of Supramolecules and Coordination Compounds

“…Based on computational structure optimizations and CCS simulations, these were assigned to closed rings ( C ) and conformationally dynamic, open structures ( E , Figure b) . Taken together, these two examples highlight the richness of structural data that can be obtained from IM, and it is anticipated that its application in synthetic laboratories and facilities will significantly increase in the future …”

“…Investigating the stability of compounds is not easily achievable with other techniques, and the unique feature of MS 2 is that solvent molecules and counterions do not interfere, making it possible to decouple these effects from the actual analyte stability. , MS n experiments (with n > 2) are possible, although not always available in commercial instruments (mostly in instruments with certain types of ion traps). This technique can investigate the disassembly and stability of already fragmented ions …”

“…The collisions determine the time the ion spends in the drift cell, and by injecting ion pulses and measuring this time, structural information is gained. The drift (or arrival) time can be converted to a collision cross section (CCS) value, which is comparable across instruments and to values computationally simulated from candidate geometries (e.g., based on density functional theory or molecular dynamics calculations). , The community has witnessed a significant increase in the use of IM; however, it is still not available or used in the majority of MS laboratories. In particular, synthetic chemists and facility technicians often do not have access to such platforms, and this technique will hence not be discussed in detail. ,,, The interested reader is referred to a recent perspective on using IM-MS for synthetic molecules …”

“…Methods adapted from native MS offer a range of advantages for their characterization over other methods: (a) an ultrahigh mass resolution that enables the unambiguous identification of composition and stoichiometry; (b) the robust analysis of complex product mixtures, where different compounds are separated by their m / z ; (c) the hyphenation with other techniques such as chromatography, , ion mobility, , or spectroscopy; , and (d) the potential to adapt characterization workflows to an industrial scale if appropriate . The characterization of supramolecular and coordination compounds using MS has been reviewed regularly, ,− including a book published by Schalley and Springer in 2009; however, MS is still not commonly and always confidently used in synthetic inorganic laboratories.…”

Modern Electrospray Ionization Mass Spectrometry Techniques for the Characterisation of Supramolecules and Coordination Compounds

“…6 Methods adapted from native MS offer a range of advantages for their characterisation over other methods: a) an ultra-high mass resolution, that enables the unambiguous identification of composition and stoichiometry, 5 b) the robust analysis of complex product mixtures, where different compounds are separated by their m/z, c) the hyphenation with other techniques such as chromatography, 7,8 ion mobility 9,10 or spectroscopy 11,12 and d) the potential to adapt characterisation workflows to an industrial scale if appropriate. 6 The characterisation of supramolecular and coordination compounds using MS has been reviewed regularly, 6,[13][14][15][16][17][18][19][20][21][22][23][24][25] including a book published by Schalley and Springer in 2009, 26 however MS is still not commonly and always confidently used in synthetic inorganic laboratories. This tutorial will focus on the practical application of MS (mostly electrospray ionization, ESI) for such inorganic complexes, beginning with technical details as well as potential challenges.…”