Investigation of Non-covalent Interactions of 18-Crown-6 with Amino Acids in Gas Phase by Mass Spectrometry

The non-covalent interactions between 18-Crown-6 (18c6) and 20 common types of protonated amino acids were explored by electrospray ionization mass spectrometry. The mass spectra showed that 18c6 could react with amino acids to form a non-covalent complexe in a stoichiometric ratio of 1:1. The calibration curves and linear equations for the complexes of L-Phe, L-Tyr, L-Lys and L-Asp with 18c6 were established by mass spectrometric titration and used as reference values for competitive ESI-MS. Through competitive equilibria, the binding constants for the complexes of 18c6 with other L-amino acids and their D-isomers were derived. It was found that, as a general trend, lgK_a for the complexes of 18c6 with the basic amino acid and the amino acid with alkyl side chain were larger than other complexes, and among the amino acid with alkyl side chain, Gly and Ala exhibited greater 18c6 binding affinities. As for Ser and Thr, the intramolecular hydrogen bond between the nitrogen atom from terminal –NH₂ and the oxygen atom from carboxyl might impede their protonated amino-group to attack the 18c6. Furthermore, Gln and Asn exhibited lower binding affinities to 18c6, probably due to effects of electron-withdrawing group of acylamide. Finally, the chiral selectivity of 18c6 for L-amino or D-amino acids were measured by ESI-MS, and the result showed that 18c6 could only recognize some neutral amino acid isomers.