D-PET Fluorescent Boronic Acids Sensors With Carbazole As The Fluorophore

As saccharides and related compounds play a significant role in the metabolic pathways of living organisms, detecting the presence and concentration of biologically important sugars (glucose, fructose, galactose, etc.) and other chiral molecules (such as a-hydroxyl carboxylic acids) in aqueous solution is necessary in a variety of medicinal and industrial contexts. Recently, boronic acid based fluorescent sensors have been designed and some of these sensors display tight binding toward sugars or polyhydroxyl acids, such as glucose, tartaric acid, mandelic acid or glucarate, etc. However, most of reported sensors which were used to detect the polyols are based on a-PET (fluorophore as the acceptor of the electron transfer, ET) mechanism. Recently, we found that carbazole-based boronic acid sensors show d-PET effect (fluorophore as the donor of the ET). d-PET effect is featured with lower background fluorescence at acidic pH than that at neutral pH, which is in stark contrast to the normal a-PET effect that shows undesired strong background fluorescence at acidic pH range, which is benefit for detection of some acidic analytes, such as hydroxyl acids at acidic pH. However, the excitation/emission wavelength of the reported sensor was short (332 nm/372 nm) and the PET fluorescence transduction efficiency was low, thus reducing the potential applicability for measurement of biological samples. Therefore, the performance of the d-PET boronic acid sensor needed to be improved. More importantly, the d-PET mechanism required detailed investigation, to determine the relationship between molecular structure and the d-PET effect to aid future sensor design.1. New phenylethynylated carbazole boronic acid sensors C1-C3 have been synthesized, which were predicted to show the novel d-PET fluorescence transduction profile (fluorophore as the electron donor of the ET), predicted by DFT/TDDFT calculations. Experimental results proved the theoretical predictions of d-PET effect for sensors C1 and C2. For sensor C3, however, no d-PET effect but the normal a-PET effect was observed. This discrepancy between the DFT/TDDFT calculations and the experimental observations can be rationalized by the free energy changes (Rehm-Weller equations) and the rate constants of the ET (kET, Marcus equation). These new d-PET boronic acid sensors show improved photophysical properties compared to the d-PET sensors reported previously. Rich fluorescence transduction was found for sensor C1, e.g. novel fluorescence enhancement/diminishment was observed for sensor C1 in the presence of mandelic acid or tartaric acid at pH 5.6. And fluorescence enhancement/diminishment was also observed in the presence of glucose or fructose at pH 7.5. The effect of pH as well as the bonding with analytes on the emission of the sensors were rationalized with DFT/TDDFT calculations.2. Other three new carbazole based fluorescent boronic acid sensors have been synthesized to investigate the fluorescence transduction efficiency of the novel d-PET effect. Arylethynyl groups were attached at the 3,6-position of the carbazole core (aryl= 4-dimethylaminophenyl for sensor C4, or phenyl for sensor C5). Model sensor C6 is without arylethynyl substitutions. Phenylboronic acid moiety was attached at the carbazole N-position in the sensors. C4 and C6 are d-PET sensors. Interestingly, C5 is an a-PET sensor and shows intensified emission at acidic pH but diminished emission at neutral/basic pH. The fluorescence modulation efficiency of the new d-PET sensors, e. g. the emission intensity enhancement of C4 upon switching the pH from acidic to neutral, is up to 10-fold, which is greatly improved compared to d-PET sensor C1 (ca.3-fold). This significant enhancement of the signal transduction efficiency was attributed to the proper orientation of the electron donor/acceptor, i.e. the dipole moment and the transition moment (the direction of PET) of the new sensors are oriented in the same direction, and the dipole moment values along the ET direction are much higher than that of the previous d-PET sensors. Selective recognition ofα-hydroxyl carboxylic acids, such as tartaric acid, were achieved with the d-PET sensors, including a novel fluorescence transduction profile of enhancement/diminishment for chemoselectivity.3. Herein, two kinds of novel chiral fluorescent boronic acid sensors PHI (phenoxazine as the fluorophore) and D1 (pyrrolo-pyrrole-dione as the fluorophore) have been synthesized. Experimental results proved that sensors PHI and D1 display d-PET effect and a-PET effect respectively. These bisboronic acids were found to be enantioselective fluorescent sensors for some analytes. For sensors PHI, the fluorescence response toward the enantiomers of tartaric acids, D-gluconic acid and D-glucose at neutral pH displayed enhancement/diminishment. Sensors D1 displayed some enantioselectivity for D-gluconic acid and D-sorbitol, however, the binding constants toward analytes were much lower.