Recent Progress in Gas Phase Cucurbit[n]uril Chemistry

Abstract

Cucurbit[n]urils (CB[n]s) are of great significance due to their unique molecular recognition properties and their potential applications in areas such as drug delivery or analytical assays. Gas phase studies, without interference from solvents or counterions, provide fundamental insights into the mechanism of CB[n] complex formation and binding. In this paper, we review the progress in gas phase CB[n] chemistry, mainly based on mass spectrometry, since 2011, including important discoveries in structural studies, mechanistic studies, and gas phase studies related to analytical or clinical applications of CB[n]s. We expect the use of gas phase methods to continue to expand and diversify.

Solvent-controlled formation of alkali and alkali-earth-secured cucurbituril/guest trimers

“…In the absence of cation, GFN2-xTB calculations show that trimerization is favorable in the gas phase (by 108.4 kcal mol −1 at 0 K and by 63.6 kcal mol −1 at 25 °C, that includes the mostly entropic penalty for aggregation, see Table 3 ). This is supported by MS experiments carried out by Da Silva 39 and Dearden 40 who have shown significant aggregation of CB[ n ]s in the gas phase. The penalty for the partial desolvation of 3 (out of 6) CB[7] portals during the trimerization is overwhelming, however (106.9 and 98.1 kcal mol −1 in water and DMSO, respectively, see Table 3 ), which makes the trimerization unfavorable in solution, in agreement with our experiments.…”

Halide Size-Selective Binding by Cucurbit[5]uril–Alkali Cation Complexes in the Gas Phase

“…Both the roughly spherical electropositive interior of the hollow CB­[ n ]–metal ion complex, and to a lesser extent the roughly circular portal that grants access to the interior, have relatively well-defined sizes that can lead to size-selective binding of spherical halide anions. Such size selectivity has frequently been observed for both neutral and cationic guests in CB­[ n ] hosts. − As the potential maps in Figure b,c suggest, CB[5] itself is probably not a good host for anions. However, the two portals of CB[5] (at the top and bottom of the ligand as oriented in the figure) are excellent cation-binding sites, and complexes of CB[5] with cations have electrostatic potentials that suggest anion binding in the host cavity should be favorable (Figure c).…”

Pseudopeptidic host adaptation in peptide recognition unveiled by ion mobility mass spectrometry

“…However, IMS-MS is still highly underexploited in the field of synthetic cages or macrocycles and their host : guest chemistry. [34][35][36][37][38][39][40][41][42][43] Herein, a combination of MS methods (single-stage, collision induced dissociation (CID) and IMS-MS experiments), fluorescence spectroscopy, NMR as well as molecular modelling of the supramolecular complexes of the Cy cages and the peptide EYE is reported to decipher the intimate details of the binding event, both in aqueous solution and in the gas-phase.…”