Chiral recognition in solution and the gas phase. Experimental and theoretical studies of aromatic D- and L-amino acid-Cu(II)-chiragen complexes.

Abstract

This study was focused on distinguishing L- and D-enantiomers of amino acids using electrospray ionization mass spectrometry (ESI-MS) of ternary complexes with Cu(II) and chiral derivatives of bipyridine. A pinene-annulated derivative of 2,2'-bipyridine, (5R,7S,8S)-(--)-5,6,7,8-tetrahydro-6,6,8-trimethyl-2-(pyridin-2-yl)-5,7-methanoquinoline, called a chiragen, was used as the auxiliary ligand bound to Cu(II) to study the complexation of D- and L-phenylalanine and D- and L-tryptophan and their detection by MS. NMR studies showed that the D- and L-amino acid complexes can be distinguished in solution by the difference in the amount of band broadening of the alpha-carbon proton, with the D-complex showing greater broadening from a more intense interaction with the paramagnetic copper center. In ESI-MS studies, the ion abundances for the analyte complexes were compared with those of internal standards to investigate competition in binding to Cu(II)chiragen between the internal standard and D- and L-amino acids. The D-Phe complex showed stronger binding than the L-Phe complex, although differences in response related to solvent effects were also apparent. In studies involving two separate internal standards, the Trp enantiomers were practically indistinguishable in all but one solvent environment. In 100% methanol, the L-Phe and D-Phe complexes were readily distinguished and the L-Phe complex out-competed the L-Phe complex by a factor of two. Density functional theory calculations were performed on D- and L-complexes of Phe and Trp to determine the optimized geometries and the most energetically favorable structures. Calculations agreed with experiments, where the D-Phe complex was the most stable structure, while the L-Trp and D-Trp complexes were comparably stable in the gas phase.