| dc.description.abstract | Theoretical modeling workflows have been established in the McLean lab to support Ion mobility-mass spectrometry (IM-MS) investigations and expanded for the structural analysis of non-covalent small molecule complexes. The main body of work focuses on the utilization of IM - MS for isomer separations and drug-host inclusion.
IM provides separation of ions based primarily on differences in size and shape, thus, IM - MS is considered a structurally selective analytical technique. However, with current IM-MS resolving powers (~60), MI enantiomer separation and detection still remains challenging. In this study, we investigate the separation of amino acids (AA) enantiomers by encouraging formation of novel bi- and tri- nuclear copper clusters in the presence of a chiral selector, that can help directly resolve enantiomers by ion mobility-mass spectrometry (IM-MS) analyses. Significant enantiomer separation was observed with peak-to-peak resolutions ranging from 0.63 (~90% overlap) to as high as 1.15 (~10% overlap). Among the investigated chiral selectors, histidine, followed by tryptophan, provided the best enantioselectivity (highest IM separation), suggesting the aromatic structure plays a vital role in forming chiral-specific ion complexes. A combination of tandem MS/MS, collisional cross section measurements, and computational modeling techniques were used to investigate the structural differences between resolvable enantiomer clusters.
There has been growing interest in the advancement of efficient and reliable analytical
methods that assist with elucidating CD host-guest drug complexation. In this study, we investigate the non-covalent ion complexes formed between naturally occurring dextrins (alpha-CD, beta-CD, gamma-CD, and maltohexaose) with the poorly water-soluble anti-malarial drug, artemisinin, using a combination of ion mobility-mass spectrometry (IM-MS), tandem MS/MS, and theoretical modeling approaches. This study aims to determine fi the drug can complex within the core dextrin cavity forming an inclusion complex or nonspecifically binds ot the periphery of the dextrins. Broad IM-MS collision cross section (CCS) mapping (n>300) and power-law regression analysis were used to confirm the stoichiometric assignments. The 1:1 drug aCD and drug: beta-CD complexes exhibit strong preferences for L+i and Na+ charge carriers, whereas drug:CD complexes preferred forming adducts with the larger alkali metals, K,+ Rb+, and Cs+. Empirical CCS measurements of the [artemisinin:beta-CD + Lilt ion correlated with predicted CCS values from the low-energy theoretical structures of the drug incorporated within the beta-CD cavity, providing further evidence that gas-phase inclusion complexes are formed in these experiments. | |
