Glucosylthioureidocalix[4]arenes: synthesis, conformations and gas-phase recognition of amino acids

The gas-phase recognition of native amino acids and the conformational properties of three glucosylthioureidocalix[4]arenes (1-3) were studied theoretically and experimentally using ab initio calculations, ESI-FTICR, 1H and 13C NMR MS. The conformational and complexation properties of the glucocalixarenes were dependent on the number of glucose units at the upper rim and the length of the alkyl chains at the lower rim of the calixarene skeleton. ESI-MS experiments showed the compounds to form 1:1 complexes with the amino acids, with a marked preference for amino acids containing an aromatic nucleus and an additional H-bonding group in their side chain (Trp, Tyr, Phe ≫ Ser, Leu and Asp). The experimental data were rationalized by the results of ab initio calculations. ESI-MS competitions carried out with enantiomeric-labelled (EL) amino acids showed enantiomeric selectivities ranging from 0.61 (Phe(D)/Phe(L) with ligand 3) to 2.58 (Tyr(D)/Tyr(L) with ligand 2). In gas-phase hydrogen-deuterium (H/D) exchange reactions, diglucosylcalix[4]arene 2 exhibited extremely slow exchange rates, which were attributed to the close proximity and strong hydrogen bonding between the facing glucosylthioureido groups. H/D exchange rates were much higher for the tetraglucosylcalix[4]arenes 1 and 3 and their amino acid complexes, and the more rigid tetrapropoxy derivative 3 showed more selective H/D exchange reactions than the calixarene 1. Bi- or trimodal H/D exchange distribution was observed for the tetraglucosyl derivatives indicating that these ligands exist in multiple isomeric forms in gas phase.