Structural Requirement for Chiral Recognition of Amino Acid by (18-Crown-6)-tetracarboxylic Acid: Binding Analysis in Solution and Solid States

Abstract

(+)-(18-Crown-6)-tetracarboxylic acid (18C6H4) is used as a chiral selector for various amino acids, where the l-isomer is usually eluted prior to the d-isomer in HPLC using 18C6H4-linked column. To clarify the structural scaffold of (+)-18C6H4 responsible for chiral separation of amino acids, we have previously investigated the interaction mode between (+)-18C6H4 and amino acids using X-ray analysis. However, no conclusive results could be obtained to explain the reverse elution order in the case of serine and to establish a general separation rule of chiral amino acid by (+)-18C6H4 in HPLC. Thus, to clarify the exceptional result obtained with serine and to set a general separation rule, interaction between (+)-18C6H4 and α-amino-n-butyric acid, valine, and alanine, as methyl substitutes of the methyl groups for the hydroxy groups of serine and threonine, and the simplest chiral amino acid, respectively, was investigated both in solution and solid states. Consequently, it was found that an asymmetric bowl-like conformation of (+)-18C6H4 is necessary for chiral separation. This conformation is constructed by chiral-specific interaction between the Cα–H groups of the amino acid and the polar oxygen atoms of (+)-18C6H4. It was also found that the exceptional reverse elution observed with serine is due to additional interaction between the polar groups of the amino acid side chain and (+)-18C6H4.

Multipodal coordination of a tetracarboxylic crown ether with ${\rm NH}_4^+$ NH 4+: A vibrational spectroscopy and computational study

“…Previous studies with x-ray crystallography and nuclear magnetic resonance spectroscopy have demonstrated the affinity of 18c6H 4 for protonated amines, amino acids, amino alcohols and further compounds with free amino functionality. [8][9][10][11][12][13][14][15][16] Those studies have provided evidence for the relevance of the barrel-like and bowl-like structures adopted by 18c6H 4 . Such structures are sustained by intramolecular H-bonding involving the carboxyl groups and by intermolecular interactions of the cationic guest with the ether and carboxyl oxygen atoms.…”

Crystal structures of amino acids: from bond lengths in glycine to metal complexes and high-pressure polymorphs

“…[108] Amino acids may also form complexes with large molecules, usually as a guest in the cavity of a macrocycle like a crown ether. [109,110] Some special attention may be devoted to a series of eight hydrogen peroxide solvates, [111,112] which are interesting in that several of them involve amino acids that do not crystallize as hydrates from aqueous solution, e.g. l-Ile·H 2 O 2 in Figure 18 (TANCES).…”

Chiral electromigration techniques in pharmaceutical and biomedical analysis

“…Analyte complexation is due to the formation of hydrogen bonds between the protonated amine and the oxygen atoms of the macrocycle. From a series of X-ray analyses employing amino acids as guest molecules Nagata and colleagues concluded that (+)-18C6H4 adopts an asymmetric C1-type conformation forming a bowl like shape [55][56][57]. The N-H and C α protons of the amino acid guest molecule interact with the oxygen atoms of the macrocycle and with the carboxylate groups of the side chains.…”