Guest‐dependent conformation of 18‐crown‐6 tetracarboxylic acid: Relation to chiral separation of racemic amino acids

Abstract

(+)-18-crown-6 tetracarboxylic acid (18C6H(4)) has been used as a chiral selector for various amines and amino acids. To further clarify the structural scaffold of 18C6H(4) for chiral separation, single crystal X-ray analysis of its glycine(+) (1), H3O+ (2), H5O2+ (3), NH4+ (4), and 2CH3NH3+ (5) complexes was performed and the guest-dependent conformation of 18C6H(4) was investigated. The crown ether ring of 18C6H4 in 3, 4, and 5 took a symmetrical C2 or C2-like conformation, whereas that in 1 and 2 took an asymmetric C1 conformation, which is commonly observed in complexes with various optically active amino acids. The overall survey of the present and related complexes suggests that the molecular conformation of 18C6H4 is freely changeable within an allowable range, depending on the molecular shape and interaction mode with the cationic guest. On the basis of the present results, we propose the allowable conformational variation of 18C6H4 and a possible transition pathway from its primary conformation to the conformation suitable for chiral separation of racemic amines and amino acids.

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

“…Alternatively, the interconversion barriers between conformer 2 and conformer 1 might be sufficiently high as to induce kinetic trapping of the higher energy conformer 2 under the present experimental conditions. 13 This would result in a non-equilibrium distribution favouring a population of conformer 2 higher than expected from energetics.…”

“…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.…”

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.…”

Chiral Separations by Capillary Electrophoresis

“…Finally, dipeptides containing branched groups were better resolved than those with straight-chain alkyl groups [81]. Recent studies [82,83] also pointed out the conformational changes that occur when (+)-18C6H 4 interacts with an amino acid [82] or with positively charged species such as glycine + , H 3 O + , H 5 O 2 + , NH 4 + , and 2CH 3 NH 3 + [83]. When interacting with amino acids, the planar/symmetric ring conformation of the selector changes into a convex/asymmetric one.…”