Ion-molecule reactions of protonated cavitands with neutral amines have been Studied using electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass, spectrometry. The cavitands studied are built by bridging a resorcin[4]arene skeleton with four aryl phosphate units. Each of the P=O bonds can be directed toward the inside or the outside of the cavity leading to six stable diastereoisomers. ESI proved to be an effective ionization method for the cavitands, although the range of ionic species observed strongly depended on the orientation of the P=O groups in the isomers and the solvent composition used. Five protonated diastereoisomers were studied in ion-molecule reactions with various types of neutral amines, arid the corresponding reaction efficiencies were:calculated. The data were compared with that observed for the complexes generated iii solution. Collision-induced dissociation (CID) was used to study the structure and relative stability of the complexes formed from different diastereomers both in solution and in the gas phase. The results clearly show that inclusion complexes are formed in the gas phase, but only for some isomers. Although all of the protonated diastereoisomers reacted with amines, the reaction rates were much lower for the diastereoisomers known to form inclusion complexes in solution. When a proton bound dimer was formed, which had the hydrogen bonding established outside the cavity, the reaction took place at the collision rate. Also, CID results confirmed the inclusion complex formation. The cavitand isomers, carrying two or more coordinating P=O groups oriented toward the inside of the cavity, proved to be strong ligands for the charged species, including the proton, organic ammonium ions, and even alkali metal cations, with cesium showing the highest affinity.