1.Chiral recognition of amino acid enantiomers by a crown ether: chiroptical IR-VCD response and computational study.
Avilés-Moreno JR1, Quesada-Moreno MM, López-González JJ, Martínez-Haya B. J Phys Chem B. 2013 Aug 15;117(32):9362-70. doi: 10.1021/jp405027s. Epub 2013 Aug 2.
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.
2.Development of HPLC Chiral Stationary Phases Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid and Their Applications.
Hyun MH1. Chirality. 2015 Sep;27(9):576-88. doi: 10.1002/chir.22484. Epub 2015 Aug 3.
Crown ether-based chiral stationary phases (CSPs) have been known to be useful for the resolution of racemic primary amino compounds. In particular, CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid have been reported to be useful for the resolution of secondary amino compounds as well as primary amino compounds. In this article, the process of developing various CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid to improve the chiral recognition efficiency and/or the stability of the CSPs and their applications to the resolution of various primary and nonprimary amino compounds are reviewed.
3.Enantioseparation and chiral recognition of α-amino acids and their derivatives on (-)-18-crown-6-tetracarboxylic acid bonded silica by capillary electrochromatography.
Wu E1, Kim KT, Adidi SK, Lee YK, Cho JW, Lee W, Kang JS. Arch Pharm Res. 2015 Aug;38(8):1499-505. doi: 10.1007/s12272-014-0507-1. Epub 2014 Nov 6.
Capillary electrochromatography was employed for enantioseparation of α-amino acids and their derivatives. (-)-18-Crown-6-2,3,11,12-tetracarboxylic acid bonded on the silica was used as the chiral stationary phase and methanol/Tris-citric acid (20 mM, pH 3.0-4.5) (20:80, v/v) was used as mobile phase. The enantioseparation performance was discussed and structure-chiral separation relationship were tried to be explained. The enantiomeric resolution was increased when the pH of the mobile phase decreased or hydrogen of amino acid was substituted with halogen. The resolution of 4-bromophenylalanine was 2.37 at pH 4.5, however, this value was increased to 3.35 at pH 3.0. Bromo- or chloro-substituted phenylalanine tended to show higher resolution than fluoro-substituted one. For fluoro-substituted phenylalanine the resolution was increased in order of 4-, 3- and 2-substituted one. α-Methyltryptamine did not show reasonable separation. As the thermodynamic study is a useful tool to understand the chiral recognition, the temperature effect on the enantioseparation was studied and the thermodynamic parameters were calculated.
4.Utilization of (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent for diamines and β-amino acids.
Rodriguez YC1, Duarte TM1, Szakonyi Z2, Forró E2, Fülöp F2, Wenzel TJ1. Chirality. 2015 Oct;27(10):708-15. doi: 10.1002/chir.22491. Epub 2015 Aug 18.
The compound (18-crown-6)-2,3,11,12-tetracarboxylic acid was evaluated as a chiral nuclear magnetic resonance (NMR) solvating agent for a series of diamines and bicyclic β-amino acids. The amine must be protonated for strong association with the crown ether. An advantage of (18-crown-6)-2,3,11,12-tetracarboxylic acid over many other crown ethers is that it undergoes a neutralization reaction with neutral amines to form the protonated species needed for binding. Twelve primary diamines in neutral and protonated forms were evaluated. Diamines with aryl and aliphatic groups were examined. Some are atropisomers with equivalent amine groups. Others have two nonequivalent amine groups. Association equilibria for these systems are complex, given the potential formation of 2:1, 1:1, and 1:2 crown-amine complexes and given the various charged species in solution for mixtures of the crown ether with the neutral amine. The crown ether produced enantiomeric differentiation in the (1) H NMR spectrum of one or more resonances for every diamine substrate.