Ion mobility mass spectrometry (IM-MS) and related gas phase techniques have a long-standing history in the field of structural biology, however their application for large synthetic molecules such as metallosupramolecular complexes remains underexplored. In this thesis, I present a workflow for the formation of polymetallic complexes in vacuo, for their structural characterisation using IM-MS in combination with computational modelling, and for the analyses of their stabilities and disassembly pathways using tandem mass spectrometry. In Chapter 1, I review a range of different techniques for the structural characterisation of supramolecular complexes, such as nuclear magnetic and electron paramagnetic resonance spectroscopy (NMR and EPR), ion mobility mass spectrometry (IM-MS), small-angle neutron and X-ray scattering (SANS and SAXS) as well as cryogenic transmission electron microscopy (cryo-TEM). Based on case studies from different fields of supramolecular chemistry, I provide an overview of their fundamental concepts, strengths and weaknesses, while highlighting how multi-technique approaches are needed for the most thorough characterisation. The chapter concludes with my evaluation that particularly IM-MS has a lot of unused potential in the field of supramolecular chemistry, and this will be the topic of the following chapters. In Chapter 2, I introduce the family of metallosupramolecular complexes discussed throughout this thesis, and investigate the fundamental stability trends and disassembly mechanisms of such polymetallic rings and rotaxanes of the type {Cr7M}, with M being a divalent heterometal. The ease of these ions to fragment is quantified using collision-induced dissociation mass spectrometry (CID-MS), and I showed that it is possible to tune their stability by varying the d-metal composition, which we rationalised with arguments from crystal field theory, and the thread end groups in the rotaxanes. I further used ion mobility to follow their disassembly processes, and in combination with density functional theory calculations, I found that the polymetallic rings dissociate to smaller rings and conformationally dynamic horseshoes, depending on the divalent metal present. For the rotaxane dissociation I observed intact polymetallic rings as fragments using IM-MS, suggesting that the ring slips off the thread without major perturbation, which is in contrast to the dimensions of the rotaxane crystal structure. Chapter 3 expands on the formation of smaller polymetallic rings in vacuo, and this has been realised by collisionally activating larger polymetallic compounds. As characterised by IM-MS and DFT calculations, the disassembly of two {CrxCu2} hourglasses (x = 10, 12) and a {Cr12Gd4} cluster leads almost exclusively to smaller rings, which are so far unseen in solution synthesis. In addition to this novel synthetic strategy, we propose a low sample-requirement workflow to evaluate the topology of polymetallic complexes based on their packing density, and this can be applied to characterise novel polymetallic compounds formed in the gas phase and to those transferred from solution. In Chapter 4, I show how the use of various charged adduct ions, which add the charge to the neutral molecules and hence enable their detection in the mass spectrometer, can influence the stability, disassembly pathway and conformational landscape of a homometallic {Cr8} ring and the {Cr7M} rotaxanes from Chapter 2. The observed trends can be applied to characterise their cavity size and transition metal properties, highlighting the potential of adduct ion studies for the characterisation of polymetallic complexes in general. The last chapter of this thesis, Chapter 5, contains my perspective on the future of IM-MS and related gas phase techniques for the characterisation of synthetic (âman-madeâ) molecules, such as (metallo)supramolecular cages, rotaxanes, interlocked molecules, polymers, dendrimers, two-dimensional architectures and host-guest complexes. IM-MS has a great potential for the direct structural investigation of such compounds, as illustrated by my experimental framework that is based on differences in the packing density of these molecules. Gas phase techniques can also aid the discovery and formation of synthetic compounds as well as enable the analysis of their stability and disassembly routes, as discussed throughout this thesis. In my view, the future of IM-MS and other advanced mass spectrometry techniques for synthetic molecules will rely on developing instrumentation, the successful coupling to computational resources, in particular machine learning, as well as the interplay to complementary and hyphenated experimental techniques, such as microscopy and chromatography.
| Date of Award | 24 Nov 2023 |
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| Original language | English |
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| Awarding Institution | - The University of Manchester
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| Supervisor | Richard Winpenny (Co Supervisor) & Perdita Barran (Main Supervisor) |
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