Design and synthesis of fluorescent ?-cyclodextrins for the enantioselective sensing of ?-amino acids

Abstract

Fluorescent monofunctionalized beta-cyclodextrins bearing a copper(II) binding side arm and a dansyl group (CD-NH-AA-CH(2)CH(2)NH-DNS) were designed as enantioselective sensors for unmodified alpha-amino acids. The side arm was derived from amino acid synthons (AA = L- and D-phenylalanine (1 and 2), L- and D-phenylglycine (3 and 4), L-proline (5), and L-cyclohexylglycine (6)) and was chosen in order to contain an amide, an amine, and a sulphonamide group. Enantioselectivity was evaluated by addition of copper(II) complexes of D- or L-valine and D- or L-proline. Chiral discrimination in the fluorescence response was observed in all cases, due to a ligand exchange process. The best conditions for these experiments were found to be the use of an excess (10:1) of the copper complex. The cyclodextrin 4 containing a D-phenylglycine unit was found to be poorly enantioselective, as found for 2, suggesting that the best design can be obtained by using L-amino acids. All L-amino acid containing cyclodextrins showed good enantioselectivities, some of which were higher than those already reported for 1. Other analytes related to amino acids were studied using cyclodextrins 1 and 3. Enantiomers of alpha,alpha-disubstituted amino acids, N-methylamino acids, and amino acid amides were found to be discriminated, while beta-phenylalanine and other molecules bearing a poor anchoring group at the alpha-carbon gave poor enantioselectivity. On the basis of the present data a model for the recognition process, based on the formation of ternary diastereomeric complexes, is proposed.

Fluorescent/luminescent detection of natural amino acids by organometallic systems

“…constrained structures (cyclohexylglycine and Pro) in the side arm is an efficient strategy for improving the enantioselectivity. Overall, the formation of a ternary diastereomer and the biasing effect of the cyclodextrin cavity in these chiral selectors were proposed [219]. The rapid, simple and low-cost technology of fluorescence microplate readers was also used to screen the samples with high enantiomeric excess using 128 [220].…”

Enantioselective Fluorescent Recognition of Free Amino Acids: Challenges and Opportunities

“…In the above study, the addition of more than 1 equiv of the amino acid led to the Cu II ion being displaced off the probe, which might contribute to the reduced enantioselectivity. To avoid this problem, fluorescence quenching of the analogous CD‐based probes 4 – 6 by the Cu II (amino acid) 2 complexes was investigated [16] 1).…”

“…In the above study,t he addition of more than 1equiv of the amino acid led to the Cu II ion being displaced off the probe,w hich might contribute to the reduced enantioselectivity.T oa void this problem, fluorescence quenching of the analogous CD-based probes 4-6 by the Cu II (amino acid) 2 complexes was investigated. [16] Theaddition of the complexes Cu II (amino acid) 2 (amino acid:p roline,v aline) to the CDbased probes led to enantioselective fluorescence quenching, which was attributed to the different stability of the resulting diastereomeric ternary CD + Cu II + amino acid complexes (Scheme 1). As shown in Scheme 1, ap entacoordinate Cu II complex could be generated from the reaction, and the chiral center on the amino acid residue of the ligands 4-6 leads to different steric interactions between the trinitrogen-based ligand and the coordinated amino acid unit derived from the two enantiomers of the amino acid substrate,t hereby giving rise to the enantioselective fluorescence quenching.T he higher the stability of the ternary complexes,t he lower their fluorescence intensity.T he highest enantioselectivity was found at a1 0:1r atio of Cu II (proline) 2 versus 6,w hich gave af luorescence intensity ratio of F L /F D = 0.264 (i.e.…”

Design, optimization and evaluation of specific affinity adsorbent for oligopeptides

“…They are water-soluble and have hydrophobic cavities into which a hydrophobic guest molecule of an appropriate size and shape can be included [7], such as adamantine [8,9], aromatic amino acid [10,11] and so on [12,13]. Recently, cyclodextrins have been widely used in many areas, including the food and pharmaceutical industries and analytical chemistry owing to their inclusion properties and excellent biocompatibility [14].…”