Enantiomeric Recognition in Host-Guest Complexation Using Chiral Bis-pyridino-18-crown-6 Ethers, by Electrospray Ionization Mass Spectrometry (ESI-MS) Enantiomer-Labelled (EL) Guest Method

Abstract

Enantiomeric recognition of chiral amino acids by synthetic and natural host compounds is one of the most challenging subjects in modern host-guest chemistry. Hostguest chiral recognition plays an important role in biological process, resolution of enantiomers, and asymmetric catalysis reactions. A number of synthetic model compounds have been designed and synthesized as chiral host molecules that help chemists understand the basis of the mechanism of host-guest complexations and their chiral recognitions. Hence, the successful design, synthesis, and application of chiral macrocyclic ligands with the selective recognition of the guests have attracted much attention for the investigations of catalysis, separations, and enzyme mimics. To determine the chiral recognition of these hosts, various methods of extraction/NMR, extraction/polarimetry, NMR titration, variable temperature NMR, nuclear overhauser effects (NOE), UV-vis titration, HPLC, capillary electrophoresis, transport, and membrane electrode have been used. A high degree of chiral recognition was observed in these studies. In the host-guest complex systems, chiral recognition has been detected by Sawada and his co-workers using fast atom bombardment mass spectrometry (FAB-MS) and electrospray ionization mass spectrometry (ESI-MS). In this reports, ESI-MS enantiomer-labeled (EL) guest method is utilized. This method requires the isotopic labeling of guest (G) enantiomers, and detects the complexation of a target host (H) compound with a 1:1 mixture of the unlabeled (GR) and labeled enantiomer guests (GS-dn). The peak intensity ratio, I[(H + GR) ]/I[(H + GS-dn), of two diasteromeric host-guest complex, which appeared simultaneously with n mass-unit difference in one ESI mass spectrum, was abbreviated as ‘IRIS’ for shot and adopted here as a critical measure for detecting chiral recognition ability. This method is a direct and operationally simple method, and it is a major feature of the stream needed for rapid screening of enantiomeric recognition. We studied the synthesis of chiral bis-pyridino-18-crown6 ethers, and the chiral recognition of α-amino acids and chiral amines by FAB-MS EL guest method, UV-vis titration, and H-NMR titration. Our interest has been focused on the enantiomeric recognition of amino acids by utilizing synthetic chiral bis-pyridino-18-crown-6 ether. We report herein the synthesis of chiral bis-pyridino-18-crown-6, (R,R,R,R)-5 and 6 with tetraethyl tetracarboxylate and tetramethyl tetracarboxamide groups as chiral barriers, and their enantiomeric recognition of several amino acid methyl ester hydrochlorides (7-16) by ESI-MS EL guest method. The IRIS values for the enantiomeric recognition of amino acid methyl ester hydrochlorides (7-16) using chiral bispyridino-18-crown-6 ether, (R,R,R,R)-5 and 6, were detected by ESI-MS EL guest method.