Investigation of Hemicryptophane Host-Guest Binding Energies Using High-Pressure Collision-Induced Dissociation in Combination with RRKM Modeling
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.
KeywordsHost-guest chemistry Cryptophanes Blackbody infrared radiative dissociation Collision-induced dissociation MassKinetics
PB acknowledges financial support from a Bourse Ministérielle awarded by the French government. DG acknowledges support from the Arcane Labex (ANR-11-LABX-0003-01). Financial support from the French National FT-ICR network (FR 3624 CNRS), and the MetaboHUB, ANR-11-INBS-0010 grant are gratefully acknowledged.
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