Supramol. Chem.

Supramolecular chemistry is the chemistry of molecular assemblies driven by noncovalent interactions. In contrast to reactions based on covalent bond formation, supramolecular assemblies are formed by noncovalent interactions which are reversible. Supramolecular chemistry is widely used in various areas of current chemistry including drug development and material science. Moreover, molecular recognitions are also the initial steps in many biological processes. For design of supramolecular systems for applications, it is important to understand the various driving forces governing the assembly processes. In the Hugh Kim’s group, we aim to understand the fundamental driving forces for supramolecular assemblies, and to apply highly specific host-guest interactions in diverse areas.

The strength of a host-guest interaction is determined by the contributions from diverse noncovalent interactions. Most important driving forces include hydrophobic interaction, electrostatic interaction, and van der Waals interactions. Additionally, loss of motional freedom upon formation of host-guest complex also affect the strength of a host-guest interaction. By combining diverse characterization methods including isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, we seek to understand the contribution from each driving force for host-guest complexations. Uniquely, we also combine mass spectrometry (MS)-based studies to understand the host-guest complexation behaviors in the gas phase where water is absent as a solvent. We use ion mobility spectrometry (IMS) and tandem MS to elucidate the structures and the stabilities of noncovalent assemblies in the gas phase and compare the gas-phase properties with the condensed-phase properties. Contrasts in the complexation behaviors in the presence and absence of water provide how water mediates host-guest interactions.

1) Differentiation and Quantification of Isomeric Molecules using Host-Guest Interactions

Distinguishing isomeric molecules in biological systems is important as they can have distinct biological roles and different chemical properties. Enzymatic and tagging strategies combined with several spectroscopy and spectrometry techniques were utilized to differentiate and quantitate these molecules, but concerns on the complex sample preparation procedures and sample loss during the process remain. Therefore, other methods for differentiation and quantification of isomeric molecules are necessary. We aim to combine host-guest chemistry with mass spectrometry to distinguish the fine-structures of isomeric molecules. Cucurbit[7]uril (CB[7]) is a macrocyclic host molecule composed of partially negative charged portals and hydrophobic inner cavity, and can interact with diverse molecules. Slight differences in the guest molecule located inside the CB[7] cavity interacts differently with CB[7] and this can generate different fragments of the complex in tandem mass spectrometry. Therefore, based on the difference from host-guest interaction, isomeric molecules can be distinguished and quantified by spectral counting using MS.

2) Enhancing the Intensities of Digested Peptides by Host-Guest Complex Formation

Proteins are the primary vehicles in body with diverse biological functions and catalytic activities. Protein sequencing is important for characterization of proteins and deducing their functions. Therefore, many methods for identifying sequence of proteins have been an attempt to study its sequence-based properties. Among them, mass spectrometry (MS)-based protein sequencing with electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are widely used due to their high sensitivity and fastness. The first step of the MS-based peptide sequencing is digesting proteins to a set of peptides using a protease. Then, these peptides are ionized by ESI or MALDI, and the mass spectrum can be used to analyze sequence of each peptides. However, some digested peptides show very low relative abundance despite the high sensitivity of this method. Therefore, it is necessary to develop a more advanced method to identify protein sequence. In this study, a host molecule is used to improve the relative abundance of specific digested peptides by forming host-guest complexes in ESI-MS and MALDI-MS. Through these studies, we aim to suggest an improved MS-based protein sequencing method using host-guest chemistry.