Structural scaffold of 18-crown-6 tetracarboxylic acid for optical resolution of chiral amino acid: X-ray crystal analyses and energy calculations of complexes of d- and l-isomers of tyrosine, isoleucine, methionine and phenylglycine

Abstract

To clarify the structural scaffold of (+)-18-crown-6 tetracarboxylic acid ((+)-18C6H4) for the optical resolution of a chiral amino acid, the crystal structures of its equimolar complexes with L- and D-isomers of tyrosine (Tyr), isoleucine (Ile), methionine (Met) and phenylglycine (PheG) were analysed by X-ray diffraction methods. (+)-18C6H4 took very similar conformations for all complexes. Although the chemical structure of (+)-18C6H4 is C2-symmetric, it took a similar asymmetric ring conformation of radius ca. 6.0 A. In all complexes, the amino group of chiral amino acids was located near the center of the ring and formed three hydrogen bonds and five electrostatic interactions with eight oxygen atoms of the ether ring and carboxyl groups. Also, the Calpha atom of chiral amino acids participated in Calpha-H...O interaction with the oxygen atom of (+)-18C6H4. In contrast, the carboxyl group of chiral amino acids did not directly interact with (+)-18C6H4. These results indicate that the structural scaffold of (+)-18C6H4 for the optical resolution of chiral amino acids is mainly based on the mode of interaction of (+)-18C6H4 with the amino and Calpha-H groups of chiral amino acids. The differences in interaction pattern and binding energy between the L- and D-isomers of each amino acid are discussed in relation to the chiral recognition of (+)-18C6H4.

Structural Scaffold of 18-Crown-6 Tetracarboxylic Acid for Optical Resolution of Chiral Amino Acid: X-Ray Crystal Analyses of Complexes of D- and L-Isomers of Serine and Glutamic Acid

“…Therefore, the elution order of D-/L-Glu suggests that the location of the a-carboxyl group and side chain of DGlu on the big and small hollows of the bowl, respectively, is more suitable for the interaction with (ϩ)-18C6H 4 than the reversed location. This agrees with the proposed chiral separation mechanism, 13) although no notable preference was suggested between the theoretical total energies of L2 and D2 complexes (Table 5). On the other hand, the comparison between L1 and D2 and between D1 and L2 shows similar location of a-carboxyl group and side chain on the bowlshaped (ϩ)-18C6H 4 , although the location of Ca-H group is rather different from each other.…”

“…On the basis of crystal structure analyses of several (ϩ)-18C6H 4 -amino acid complexes reported so far, we proposed a possible chiral separation mechanism 13) for the first elution rule of L-amino acid in HPLC using (ϩ)-18C6H 4 column, that is, (ϩ)-18C6H 4 molecule forms a bowl-shaped figure with two concave and one convex rim, and the location of amino acid on this asymmetric figure leads to the different binding mode between L-and D-enantiomers, especially for the interaction pattern of the N-H and Ca-H groups with respect to (ϩ)-18C6H 4 , in which the binding energy is advantageous for D-enantiomer rather than L-enantiomer. The schematic binding patterns of (Fig.…”

“…As for the convex and asymmetric conformation of (ϩ)-18C6H 4 molecule, we previously reported 13) that it can be grouped into three types, "conformers I, II and III", according to the orientation around the C(10)…”

“…It may say that their conformers are energetically stable and are dependent on the interaction with guest molecule, because the same conformers have also been observed in the complexes with other amine compounds. 13,16) All of amino acids took a cationic form, where a-amino and a-carboxyl groups were protonated and not deprotonated, respectively, and the hydroxyl and g-carboxyl groups of chiral Ser and Glu side chains were not deprotonated despite of their different chiralities. The molecular conformations of L-and D-Ser are in the usually observed range.…”

“…[17][18][19] Some conformational features are; and carboxyl groups) with (ϩ)-18C6H 4 are very similar to each other despite their different chiralities, and such similarities were also observed in the Tyr, Ile, Met, and phenylglycine. 13) The amino groups of Ser and Glu were located near at the center of the hemisphere of radiusϭca. 6.0 Å, which were created with eight oxygen atoms of crown ether ring and carboxyl group of (ϩ)-18C6H 4 , and formed the N-H···O hydrogen bonds and/or N···O electrostatic interactions with seven to eight oxygen atoms ( Table 2).…”