Enantioselective and Chemoselective Fluorescent Recognition of Chiral Amino Acids

Author: ORCID icon orcid.org/0009-0007-3254-9363
Mao, Yifan, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Pu, Lin, AS-Chemistry (CHEM), University of Virginia

1,1'-Bi-2-naphthol (BINOL) serves as an excellent core structure for the design of enantioselective fluorescent probes. Owing to its unique chiral fluorophore structure and outstanding functionalization capacity, BINOL offers immense potential for the development of chiral fluorescent sensing. In this thesis, several BINOL-based fluorescent probes are presented, exhibiting good enantioselectivity and chemoselectivity for the recognition of amino acids—molecules that possess significant biofunctions and have broad applications in various areas, including asymmetric catalysis.
A chemoselective and enantioselective fluorescent probe has been developed to determine both the concentration and enantiomeric composition of the biologically important amino acid histidine by measuring fluorescence responses (λ = 470 and 560 nm) when excited at two different wavelengths.
It has been discovered that one enantiomer of a chiral substrate can greatly enhance the fluorescence of a molecular probe at one emitting signal (λ = 517 nm), while the opposite enantiomer of the substrate significantly enhances the fluorescence of the same probe at a distinctively different emission (λ = 575 nm). Under slightly acidic conditions, this probe, which is composed of a BINOL-based chiral di-aldehyde, exhibits a chemoselective and enantioselective fluorescent response toward histidine when combined with Zn(II). The opposite enantioselective fluorescent responses of the probe at two emissions allow the determination of both the concentration and the enantiomeric composition of the substrate using a single probe. Mechanistic studies have revealed two distinct reaction pathways when treating the probe with the two enantiomers of the substrate. These reaction pathways generate two different products, one dimeric and another polymeric, each exhibiting very different emissions.
Utilizing the dynamic covalent chemistry of imines, a regioselective and enantioselective synthesis of an unsymmetric (C1) chiral macrocycle has been conducted from the reaction of an unsymmetric (C1) chiral dialdehyde probe, containing a salicylaldehyde unit and a benzaldehyde unit, with lysine, an unsymmetric (C1) chiral diamine. The enantioselectivity is further enhanced in the presence of Zn(II). This probe, in combination with Zn(II), is found to be a highly chemoselective and enantioselective fluorescent probe for lysine, capable of detecting specific enantiomers of this amino acid.

PHD (Doctor of Philosophy)
Fluorescence, Amino Acids, Enantioselectivity, Chemoselectivity, Regioselectivity, Probes, Macrocycles, Organic Chemistry
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