Chiral Recognition of Amino Acid Enantiomers by a Crown Ether: Chiroptical IR-VCD Response and Computational Study

Abstract

We report on a combined experimental and computational study of the chiral recognition of the amino acid serine in protonated form (L/D-SerH(+)), by the crown ether (all-S)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (S-18c6H4). Infrared and vibrational circular dichroism spectroscopies (IR-VCD) are employed to characterize the chiroptical response of the complexes formed by S-18c6H4 with the L-SerH(+) and D-SerH(+) enantiomers in dried thin films obtained from aqueous solutions. The study focuses on vibrational modes directly related to the intermolecular hydrogen bonds between the crown ether derivative and serine, responsible for crown-serine binding, namely, the C═O and C-O stretching modes, and on the C-O-H bending mode, which yield intense IR and VCD signals in the range of wavenumbers 900-2000 cm(-1). The experimental spectra are analyzed in combination with a computational structural survey and optimization at different levels of density functional theory. The conformational landscape of the complexes is found to be primarily governed by a bowl-like structure of the crown ether host and a tripodal coordination of the protonated R-NH3(+) group of serine with the oxygen atoms of the central ether ring. Additionally, one or two of the carboxylic side groups of the crown ether interact with the -COH and -COOH groups of serine. Chiral selectivity is probed by recording the IR and VCD spectra of dried thin films obtained from aqueous solutions with equimolar concentrations of the two serine enantiomers and the macrocycle. The results demonstrate a marked chiral recognition of L-SerH(+) relative to D-SerH(+) by the S-18c6H4 substrate, which arises from the favorable host-guest coordination through H-bonds at optimum distances and collinear orientations, also involving a limited distortion of the crown ether backbone.