In this dissertation, I use Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to study the structure and energetics of gas phase ions. Infrared multiphoton dissociation spectroscopy (IRMPD) is a technique for measuring the IR spectrum of gas phase ions in a Penning trap. I use this technique to investigate the conformation of cucurbituril complexes, terminal diamines, and protonated amino acids. Cross sectional areas by Fourier transform ion cyclotron resonance mass spectrometry (CRAFTI) is a technique developed by the Dearden lab to measure the cross section of gas phase ions. In this work, I further develop a fundamental understanding of this technique. I investigate the role that dissociation plays in this and other FTICR-MS techniques. I also show that the principles of the CRAFTI technique can be used to measure the pressure inside the cell of an FTICR-MS. This technique, linewidth pressure measurement (LIPS), allows for a quantitative measurement and comparison of CRAFTI cross sections. To demonstrate the improvements to the technique, I measure the CRAFTI cross sections for the 20 standard amino acids and compare these to literature values measured by ion mobility measurements.

This dissertation investigates Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) based techniques to study the impact of molecular structure on conformation and binding energetics. A novel method to determine collison cross sectional areas using FTICR (CRAFTI), initially developed by the Dearden lab, was applied to study the conformations of molecular systems with unique structural attributes in an attempt to explore the molecular range of CRAFTI. The systems chosen for CRAFTI studies include crown-ether alkylammonium complexes and biogenic amino acids. The results were found to be consistent with expected behavior, and strongly correlated with experimental measurements made using ion mobility spectrometry (IMS) and predictions from computations. The analytical sensitivity of CRAFTI was highlighted by its ability to distinguish the normal and branched structural isomers of butylamine. Besides conformation characterization, quantitative evaluation of binding was undertaken on metal ion-cryptand complexes on the FTICR instrument using sustained off-resonance irradiation-collision-induced dissociation (SORI CID) method. Complex formation and dissociation was found to be a strong function of both guest and host sizes which impacted steric selectivity, and polarizability. The results demonstrate the ability of FTICR to simultaneously determine structure, conformation and binding thereby providing comprehensive molecular characterization.

In my dissertation, I use a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) to investigate supramolecules. Cross-sectional areas by Fourier transform ICR (CRAFTI), a novel technique for measurements of collision cross sections by FTICR, is demonstrated for the first time. The CRAFTI method measures the total "dephasing cross section" for removal of the ions from the coherent packet in the FTICR cell, including contributions not only from momentum transfer but also from reactive collisions including those leading to collisional dissociation. Experimental CRAFTI collision cross sections correlate linearly with theoretically computed results and with results obtained using ion mobility measurements. Different collision gases, including Xe, N2, Ar, and SF6, are all appropriate for the CRAFTI technique when the experiments are done at proper kinetic energies. The CRAFTI technique was applied to characterize the molecular shape of complexes of alkyl mono- and n-alkyldiamine with cucurbit[n]uril in the gas phase. The CRAFTI results are consistent with corresponding computational geometries. The CRAFTI technique was combined with SORI-CID (sustained off-resonance irradiation collision induced dissociation) for characterization of complexes of α,ω-alkyldiammonium with cucurbit[n]urils (n=5, 7 and 8) and cucurbituril derivatives. The results demonstrate that for bigger cucurbiturils, the complexes have the alkyldiamine tails threaded through the cavity of the host; for smaller cucurbiturils, the complexes have the tails of the alklydiamines external to the portal of the host.Capping molecules for larger CBn to form larger containers were also investigated. Using SORI-CID methods, CB7, a bigger cucurbituril cage, was found to form a more stable complex with Gu+ (guanidinium). Several neutral guests (benzene, fluorobenzene and toluene) were trapped in CB7 cavity to form inclusion complexes.

In this dissertation, I used Fourier transform ion cyclotron resonance mass spectrometry (FTICR) and ion mobility spectrometry (IMS) to study the structure and energetics of supramolecular complex ions in the gas phase. Using the CRAFTI (cross sectional areas by Fourier transform ion cyclotron resonance) technique developed by Dearden’s lab we observed that complexes with alkali cations capping the portals of cucurbit[5]uril (CB[5]) bind halide anions size-selectively in the gas phase. Our data suggest that Cl– binds inside the CB[5] cavity, Br– binds both inside (with Na+ions capping the portals of CB[5]) and outside (when K+caps CB[5]), and I– binds weakly outside. Although geometry optimization at the M06-2X/6-31+G* level of ab initio theory suggests internal anion binding is energetically favored over external binding, we believe the externally-bound complexes observed experimentally must be due to large energetic barriers hindering the passing of large anions through the CB[5] portal, preventing access to the interior. Calculation of the barriers to anion egress using MMFF//M06-2X/6-31+G* theory supports this idea. Collision cross section (CCS) measurements using the CRAFTI method for CB[5] complexes with various alkali metals and different neutral guests (methanol, ethanol, formic acid, and acetonitrile) along with the results of mass spectra from FTICR show that both the sizes and the resulting charge densities of the alkali metal ions affect the relative tendency of the guests to bind inside CB[5]. The CCS values suggest that methanol, formic acid, and acetonitrile are internally bound CB[5] while ethanol is bound outside the CB[5] host. The relative abundances of the paired peaks in the obtained mass spectra indicate that the inclusion of formic acid and methanol are enhanced when K+ ions cap the complexes, whereas the inclusion of acetonitrile is enhanced when Cs+ ions cap the complexes. The relative abundance of ethanol complexes increases when Na+ ions cap the complexes. CRAFTI CCS values for singly- and doubly-charged cucurbit[n]uril (n = 5, 6, and 7), decamethylcucurbit[5]uril (mc5), and cyclohexanocucurbit[5]uril (CB*[5]) complexes of alkali metal cations (Li+-Cs+) show +2 complex ions have CCS values ranging between 94-105% of those of their +1 counterparts (increasing with metal ion size). These results are consistent with CCS values were calculated using the projection approximation (PA). Ion mobility measurements of the same complexes find the CCS of +2 complexes to be in all cases 9-12% larger than those of the corresponding +1 complexes, with little metal ion dependence. Trajectory method (TM) calculations of CCS for the same structures consistently yield values 7-10% larger for the +2 complexes than for the corresponding +1 complexes and little metal ion dependence which agrees with experimental values.

This dissertation investigates non-covalent macromolecular chemistry using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) based techniques. The included studies reveal the impact of molecular structure on conformation and binding energetics. Supramolecules that might be too heavy to be dissociated in single collision-induced dissociation (CID) were dissociated using sustained off-resonance collision induced dissociation (SORI-CID) techniques. Relative binding energies and thresholds were evaluated for various macromolecular host-guest systems. Besides the non-covalent binding energies, conformation characterization was undertaken by a novel method to determine collision cross sectional areas using FTICR (CRAFTI, and multi-CRAFTI), initially developed by the Dearden lab. The systems chosen for further understanding of macromolecular interactions include calixarene-alkali metal complexes, cucurbit[5]uril-alkali halide complexes and cryptand-alkali metal complexes. The results were found to be consistent with expected behavior, and strongly correlated with predictions from computations. Size- and shape selectivity, as well as host-guest polarizability, are the main factors that govern the non-covalent macromolecular interactions that control complex conformation and dissociation. The results demonstrate the ability of FTICR to simultaneously determine binding energy, structure and conformation, which are the most important aspects for determination of comprehensive molecular characterization.

This dissertation expounds on the investigations of the structure and chemistry of peptides and supramolecular host-guest systems in the gas phase. These investigations used two different kinds of analytical instrument: Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and ion mobility mass spectrometry (IM-MS, IMS). These investigations were complemented by chemical modeling. The FTICR was used to radially trap ions with its 4.7 T magnet, which allowed the ions to undergo sustained off-resonance irradiation collision-induced dissociation (SORI-CID). A subsequent event then measured the collision cross sections (σ) of the targeted precursor ion and one of the selected product ions. These experiments were repeated multiple times to measure σ for as many precursor/product pairs as possible. A similar kind of experiment was performed in the IM-MS instrument, through in-source collision-induced dissociation and size-based ion separation in the instrument’s mobility region. When the precursor/product σ ratios were compared, the values obtained by both methods were in good agreement with each other. Application of the FTICR-based technique to [2.2.2]-cryptand+Cs+ caused the externally bound Cs+ to migrate into the cryptand’s cavity. Further development of the FTICR-based technique allowed me to perform the post-SORI σ measurements in a time-resolved fashion. Data collected in this manner revealed that collisionally activated peptides refold over a 5 – 10 second timescale, as determined by their σ shrinking with time. These experiments allowed for observation of a peptide refolding. The IM-MS instrument was applied to a supramolecular chemistry problem surrounding cucurbit[7]uril (CB7), and its ability to bind two identical guests within its cavity. Literature precedent and conventional wisdom suggested that only one guest would bind within CB7’s cavity while the other guest would be bound externally. When ion mobility cross sections (Ω) were obtained for [CB7 + Guest2]2+ systems, it was discovered that both guests could be bound within CB7’s cavity. This was possible because the guests possessed the correct shape and chemistry to favor dispersive interactions between CB7’s cavity and the adjacent guest, and ion-dipole interactions with CB7’s carbonyl-lined portal.

This dissertation focuses on the investigation of gas-phase characteristics of cucurbituril host-guest systems using ion mobility spectrometry (IMS) and related techniques. Collision cross-sections (CCS) of alkylammonium complexes of cucurbit[n]uril (CB[n]) are measured to understand the allosteric interactions that induce conformational changes in the complex in the presence of metal cations on one of the portals of the cucurbit[6]uril (CB[6]) host. Cationic species on one CB[6] rim sterically force longer linear alkylammonium guests out of the cucurbituril cavity during complex formation. Similarly, rigid cucurbituril-metal complexes were studied using IMS to demonstrate the effect of long-range ion-neutral interactions on the gas phase mobility of ions. The contributions of charge state and charge distribution to the ion mobility CCS measured using a drift tube ion mobility spectrometer (DTIMS) were studied. This IMS method characterization will help in the study of biomolecules and may answer some of the questions regarding CCS measurements in protein structures, that are still being debated. While most of the studies were done using an IMS system, this dissertation also includes gas phase characterization studies done using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. A novel gas-phase CCS measurement technique - cross sectional areas using Fourier transform ion cyclotron resonance mass spectrometry (CRAFTI) was attempted on bigger systems like the [cucurbit[6]uril-n-alkylammonium]+ complexes. Infrared multi-photon dissociation (IRMPD), collision induced dissociation (CID), and sustained off-resonance irradiation (SORI) studies were done on many CB[n] systems, which helped to extract useful structural information about the complexes.

Heterobimetallic catalysts offer large potential for efficient and selective catalysis of a wide range of reactions. Better understanding of these catalytic mechanisms could yield further improvement in their catalytic abilities. Cp(CO)2Fe-Cu(IPr) (IPr = N,N-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) is a catalyst that has been reported to catalyze arene borylation. The catalytic mechanism of this catalyst that had been previously proposed had the initial step being a metal-metal cleavage. However, computational modeling suggested an alternate mechanism that could be more energetically favorable. Rather than a metal-metal cleavage as the initial step, we proposed a photoactivated carbonyl dissociation. To support this proposition, we performed time resolved Fourier transform infrared spectroscopy experiments that found evidence supporting our proposed mechanism. Based on these experimental results, we have proposed a new catalytic cycle. The determination of collisional cross section is a powerful tool in analytical chemistry for distinguishing isomers. Techniques such as ion mobility spectrometry can be used to find the collisional cross section of ions but require specialized equipment. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry is a widely used technique for determining ion mass. A technique known as CRoss sectional Area from Fourier Transform Ion cyclotron resonance (CRAFTI) uses a standard FTICR instrument to measure the collisional cross section of ions. This is done by performing a Fourier transform on the data and measuring the Lorenztian width of the peak at the resonant frequency and relating that to the exponential decay of the signal in the time domain. We developed a new data analysis technique that is able to extract just the signal at the resonant frequency in the time domain and directly fit the exponential decay. This new data analysis technique opens new possibilities for expanding the capabilities of CRAFTI measurements, including simultaneous measurement of isomers and a new experimental technique that could measure ions above the mass limit of traditional CRAFTI measurements.

This thesis explores the structures and structural changes of supramolecular host-guest systems, proteins, and other small molecules in the gas phase, utilizing a combination of computational modeling and experimental data. The primary instruments employed were a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) and an ion mobility mass spectrometer (IM-MS). In the IM-MS experiments, the focus was on investigating the binding behavior of cyclodextrin macrocycles—specifically α, β, and γ-cyclodextrin—with per-fluoroalkane substances (PFAS), which are pervasive environmental contaminants. This investigation involved measuring ion-neutral collision cross sections and using computational modeling to determine whether PFAS compounds bind inside or outside the cyclodextrin cavity. The results indicate that only β-cyclodextrin binds PFAS compounds internally, attributed to its seven-fold symmetry and the localized hydrogen bonding network across the macrocycle's secondary face. Conversely, α and γ-cyclodextrin appear to favor collapsing inward, enhancing internal hydrogen bonding while keeping the PFAS bound externally. The FTICR-MS instrument was used for time-resolved CRAFTI (TR-CRAFTI) collision cross section measurements on various systems, including tetraalkylammoniums (TAA), cytochrome C, and β-cyclodextrin host-guest complexes. This involved activating gas-phase ions using sustained off-resonance irradiation (SORI) activation, followed by a variable delay for collisional cooling. Subsequently, a CRAFTI measurement was conducted to obtain a timeresolved view of the collision cross section. Initial findings suggest the feasibility of measuring and modeling structural changes post-activation over varying time scales, ranging from approximately 100 milliseconds to 10 seconds, depending on the size and complexity of the system being studied.