Synthesis And Properties Of Chiral D-PET Boronic Acid Fluorescent Sensors

Chiral a-hydroxy acids are widely used in the molecular synthesis of natural products and drugs. For instance, tartaric acids are significant chiral ligands in many well-known chiral catalysts and as the chiral source in the molecular synthesis of complex natural products. Mandelic acids are also important medical intermediates.Currently the chiral boronic acid fluorescent sensors used for chiral recognition of a-hydroxy acids in aqueous solution are mainly based on acceptor photoinduced electron transfer (a-PET) mechanism. a-PET boronic acid fluorescent sensors can achieved good chiral recognition of a-hydroxy acids in the neutral and basic pH regions. However, these a-PeT boronic acid sensors do not work well in the acidic pH region due to the strong background fluorescence, effective recognition can not be achieved. The donor photoinduced electron transfer (d-PET) boronic acid fluorescent sensors can make up for deficiencies in this area properly. In the acidic pH region, the d-PET fluorescent sensors with weak background fluorescence can get a fluorescence enhancement after binding with a-hydroxy acids, so as to achieve the purpose of chiral recognition. However, so far there is only one reported chiral d-PET diboronic acid sensor used for recognition of a-hydroxy acids. The excitation and emission wavelengths of the fluorescent sensor are in the ultraviolet region and with little efficiency of PET. It needs to be improved in order to achieve good chiral recognition of a-hydroxy acids.First, we synthesized a chiral d-PET boronic acid fluorescent sensor A1 by introduction of strong donor thiophene as conjugated linking group on the basis of reported sensor 52. Compared to sensor 52, sensor A1 is red-shifted to visible region and the efficiency of d-PET is enhanced. Sensor A1 achieved the chiral recognition of tartaric acid and mandelic acid in the acidic pH region. Sensor A1 is also the first boronic acid fluorescent sensor which can recognize the chiral mandelic acid in aqueous solutions.Secondly, we selected phenothiazine as the fluorophore because of its well-known strong electron-donating ability. We introduced C=C to the phenothiazine fluorophore to extendπ-conjugation and improve the photophysical properties. We synthesized five boronic acid fluorescent sensors B1-B5 based on phenothiazine fluorophore. The emission band is centered at 448-489 run. A Stokes shift of 59-140 nm was observed. d-PeT effect was observed for sensor B5. The efficiency of d-PET sensor B5 is 1.5. Sensor B5 could recognize tartaric acid and mandelic acid effectively in the acidic pH region.Modular approach was used to design modular chiral d-PET boronic acid fluorescent sensor C1 based on sensor B5. The efficiency of d-PET sensor C1 increases to 7.0, and the chiral recognition of tartaric acid was obtained at acidic pH. We designed another modular chiral d-PET boronic acid fluorescent sensor C2. The efficiency of d-PET sensor C2 increases to 8.6, and at acidic pH, improved chiral recognition of tartaric acid shows that the modular approach is a reasonable and efficient sensor design method. A consecutive fluorescence enhancement/decrease was observed, thus we propose a transition of the binding stoichiometry from 1:1 to 1:2 as the tartaric acid concentration increases, which is supported by mass spectra analysis.