Fluorescent Recognition of Amino Acids: A Micelle Approach

1,1’-Bi-2-naphthol (BINOL)-based fluorescent probes have been developed as powerful tools for the molecular recognition of many chiral molecules. High sensitivity and enantioselectivity for chiral amino acids have been achieved in organic media, but the recognition in water media has been limited by their poor solubility in aqueous solution.
By using a diblock copolymer PEG-PLLA, 3,3’-diformyl-BINOL was encapsulated into micelles to form a micelle probe. It allowed the detection of chiral lysine (Lys) both chemoselectively and enantioselectively in carbonate buffer solution. A limit of detection (LOD) of 848 nM and 2nd order fit of ee detection was obtained for D-Lys. The chemoselectivity was attributed to the selective reaction of Lys’s terminal amino groups with the probe.
Series of monoformyl-BINOL with varying substituents were synthesized and engineered into micelle probes. These probes achieved specific detection of chiral tryptophan (Trp) both enantioselectively and chemoselectively in carbonate buffer solution, with LOD of 2.6 µM and 1st order fit of ee detection.
A non-C2 symmetric molecule, 3,3’-diformyl-tetrahydro-BINOL, was fabricated into a micelle probe. It achieved specific detection of chiral His both enantioselectively and chemoselectively in carbonate buffer solution, with LOD of 107 nM and 2nd order fit of ee detection.
Several copolymers were screened to form various micelle probes with the same 3,3’-diformyl-BINOL core. Among these copolymer-based micelles, the probe made of a triblock copolymer F68 achieved specific detection of chiral Trp both enantioselectively and chemoselectively in carbonate buffer solution, with LOD of 962 nM and 3rd order fit of ee detection.
This work demonstrates that the micelles made of the block polymers not only allow the use of water insoluble probes for fluorescent detection of amino acids in aqueous solution, but also provide unique microenvironments to tune and enhance the sensitivity and selectivity of these probes in fluorescent recognition. It provides a new strategy for the development of chemoselective as well as enantioselective fluorescent probes for various applications.