Host–Guest Chemistry in the Gas Phase: Selected Fragmentations of CB[6]–Peptide Complexes at Lysine Residues and Its Utility to Probe the Structures of Small Proteins

The gas phase host–guest chemistry between cucurbit[6]uril (CB[6]) and peptide is investigated using electrospray ionization mass spectrometry (ESI-MS). CB[6] exhibits a high preference to interacting with a Lys residue in a peptide forming a CB[6]–peptide complex. Collisionally activated CB[6] complexes of peptides yield a common highly selective fragment product at <i>m</i>/<i>z</i> 549.2, corresponding to the doubly charged CB[6] complex of 5-iminiopentylammonium (5IPA). The process involves the formation of an internal iminium ion, which results from further fragments to an a-type ion from a y-type ion, and the resulting 5IPA ion threads through CB[6]. Numerous peptides are investigated to test the generality of the observed unique host–guest chemistry of CB[6]. Its potential utility in probing protein structures is demonstrated using CB[6] complexes of ubiquitin. Low-energy collision induced dissociation yields CB[6] complex fragments, and further MS<sup><i>n</i></sup> spectra reveal details of the CB[6] binding sites, which allow us to deduce the protein structure in the solution phase. The mechanisms and energetics of the observed reactions are evaluated using density functional theory calculations.