Investigation of Hemicryptophane Host-Guest Binding Energies Using High-Pressure Collision-Induced Dissociation in Combination with RRKM Modeling

• Published in: Journal of the American Society for Mass Spectrometry Vol. 30; no. 3; pp. 509 - 518
• Main Authors: Bayat, Parisa, Gatineau, David, Lesage, Denis, Robert, Vincent, Martinez, Alexandre, Cole, Richard B.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2019; Springer Nature B.V; American Chemical Society
• Subjects: Analytical Chemistry; Bioinformatics; Biotechnology; Black body radiation; Cages; Chemical Sciences; Chemical synthesis; Chemistry; Chemistry and Materials Science; Choline; Fluorescence; Linkages; Mass spectrometry; Modelling; NMR; Nuclear magnetic resonance; or physical chemistry; Organic Chemistry; Proteomics; Research Article; Selectivity; Theoretical and; Cryptophanes; Collision-induced dissociation; MassKinetics; Host-guest chemistry; Blackbody infrared radiative dissociation; MassKinetics 2; blackbody infrared radiative dissociation; Host-Guest chemistry; collision induced dissociation; cryptophanes
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1007/s13361-018-2109-5

In advancing host-guest (H-G) chemistry, considerable effort has been spent to synthesize host molecules with specific and well-defined molecular recognition characteristics including selectivity and adjustable affinity. An important step in the process is the characterization of binding strengths of the H-G complexes that is typically performed in solution using NMR or fluorescence. Here, we present a mass spectrometry-based multimodal approach to obtain critical energies of dissociation for two hemicryptophane cages with three biologically relevant guest molecules. A combination of blackbody infrared radiative dissociation (BIRD) and high-pressure collision-induced dissociation (high-pressure CID), along with RRKM modeling, was employed for this purpose. For the two tested hemicryptophane hosts, the cage containing naphthyl linkages exhibited stronger interactions than the cage bearing phenyl linkages. For both cages, the order of guest stability is choline > acetylcholine > betaine. The information obtained by these types of mass spectrometric studies can provide new insight into the structural features that most influence the stability of H-G pairs, thereby providing guidance for future syntheses.
Graphical Abstract