Chiral molecular recognition: a 19F nuclear magnetic resonance study of the diastereoisomer inclusion complexes formed between fluorinated amino acid derivatives and α-cyclodextrin in aqueous solution

Abstract

A ¹⁹F NMR spectroscopic study (282.35 MHz) of the formation of diastereoisomeric inclusion complexes by fluorinated amino acid derivatives and α-cyclodextrin (αCD) in 10% aqueous D₂O solution yields the apparent stability constants K_R and K_S/dm³ mol^–1= 7.7 ± 0.3 and 8.2 ± 0.3 for protonated α-(p-fluorophenyl)glycine (1 + H), 21.5 ± 0.4 and 22.5 ± 0.4 for deprotonated α–(p-fluorophenyl)glycine (1 – H), 14.4 ± 0.1 and 14.6 ± 0.1 for N-acetyl-α-(p-fluorophenyl)glycine (2), 13.1 ± 0.5 and 14.1 ± 0.5 for deprotonated N-acetyl-α-(p-fluorophenyl)-glycine (2– H), and 12.4 ± 0.3 and 10.6 ± 0.4 for deprotonated N-(p-fluorobenzoyl)valine (3– H), where the first and second of each pair of values refers to the diastereoisomer formed between αCD and the R and S enantiomer, respectively. The chemical shifts of the R-amino acid derivative ·αCD inclusion complexes are upfield from those of their S analogues for deprotonated N-(p-fluorobenzoyl)valine (3– H), deprotonated α-(p-fluorophenyl)glycine (1– H), and deprotonated N-acetyl-α-(p-fluorophenyl)glycine (2– H), but this relationship is reversed for protonated α-(p-fluorophenyl)glycine (1+ H) and N-acetyl-α-(p-fluorophenyl)glycine (2+ H). In the case of the N-(p-fluorobenzoyl)valine ·αCD inclusion complex (3·αCD) the chemical shift difference between the diastereo-isomers formed with the R and S enantiomers is too small for quantitative analysis and accordingly a composite K_R,S/dm³ mol^–1= 8.3 ± 0.3 was determined. The factors causing the variations in apparent stability constants and chemical shifts are discussed.