Design, Synthesis And Mechanism Study Of Sulfonamide Derivatives As Fluorescent Sensors For Mercury Ions

Mercury pollution, which mainly stems from mercury (II) ion (Hg2+) contaminated natural water, has become a worldwide environment problem since Hg2+ can easily pass through biological membranes, causing serious damage to the central nervous and endocrine systems. Therefore, developing new methods for mercury detection that are effective, rapid, facile, and applicable to environmental and/or biological systems have become a significant and insistent goal. Differently from traditional instrumental techniques, small-molecule probes are well-suited for quick detection of Hg2+ in the field and for in vivo studies in biological systems. And therefore the design and synthesis of fluorescence sensors for Hg2+ have recently attracted much attention. Because of the water-solubility is very important for sensors, hydrophilic amino acids have been introduced to the design to improve the water-solubility of fluorescent sensors.Firstly, we designed and synthesized methyl 2-(5-(dimethylamino)naphthalene- 1- sulfonamido)-3-(1H-indol-3-yl)propanoate (a) as an efficient and selective fluorescent Hg2+ probe. Compound a displayed a rapid and specific response to Hg2+ in buffered aqueous solution with enhancement and blue-shift of fluorescence emission, and in compare to the previous study it showed a significant improvement of detection limit (5 nM), which is lower than the upper limit for Hg2+ in drinking water (10 nM). Notably, the results of the fluorescence imaging in Hela cells suggest that a can be used to detect intracellular Hg2+ in live cells. Using 1H NMR, FT-IR and single crystal X-ray diffraction experiments, we explored the coordination mechanism of a and Hg2+ both in solution and in crystal. On the basis of these results, we confirmed that the blue-shift and enhancement of the emission band of a originated from the strong binding between Hg2+ and the deprotonated amino group, which induced the disruption of ICT between the amino group and the dansyl moiety. The high stability of a/Hg2+ complex in aqueous solution could be attributed to the enhanced chelation of the nitrogen atom and Hg2+, various weak interactions provided by multiple atoms, and also by the fixed placement in space of Hg2+ by the two indole rings. In summary, the sensor a exhibits characteristics of high affinity, fast and stably turn-on response to Hg2+, which attribute to the stably binding modle of a/Hg2+.Based on the investigation of a, we have designed and synthesized other two new sensors, dimethyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)succinate (b) and dimethyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)pentanedioate (c), with diester groups which act as the Hg2+ recognition site and the dansyl group as the fluorescent chromophore. As the closely related structure, b and c show similar fluorescence response to Hg2+ with large blue-shift (Δλ=75 nm) and quantum yield 10-fold enhancement , performing high sensitivity (detection limit 0.5μM) and specific selectivity for Hg2+ over 15 other metal ions in HEPES solution. We also examined the coordination mechanism of b and Hg2+ in solution with 1H NMR and FT-IR experiments, which show that the involved ICT between the amino group and the dansyl moiety is inhibited by Hg2+ binding, and therefore the emission is released and the band shifts toward the blue region of the emission spectrum. The dimethyl amino group of the dansyl moiety is weakly basic, while the amino functionality of the sulfonamide is weakly acidic, resulting in a sensor with good water compatibility. Upon addition of low amounts of Hg2+ to b in solution, the deprotonated sulfonamide has a higher affinity for Hg2+ and bind Hg2+ to form a complex of b/Hg2+; while large amounts of Hg2+ induces low water-solubility and aggregated complexes with strong fluorescence emission and blue-shift, which can be used to remove Hg2+ from aqueous solution by filtering.The previous studies revealed that both the sulfonamide group and the residue of amino acid were very important for the Hg2+ recognition. To further assayed it, we design and synthesize a series of amino acid derivatives, methyl 2-(5-(dimethylamino)naphthalene- 1-sulfonamido)-4-methylpentanoate (d), 2-(5-(dimethylamino)naphthalene-1-sulfonamido)- 4-methylpentanoic acid (e), N-(cyanomethyl)-2-(5-(dimethylamino)naphthalene-1-sulfonamido)-4- methyl pentanamide (f), 2-(biphenyl-4-ylsulfonamido)-N-(cyanomethyl)-4-methyl pentanamide (g), N-(1-(cyanomethylamino)-4-methyl-1-oxopentan-2-yl)-4- methoxybenzamide (h) and N-(1-(cyanomethylamino)-4-methyl-1-oxopentan-2-yl) biphenyl -4-carboxamide (i). Compound h and i did not respond to Hg2+ in HEPES aqueous solution, correspondingly d, e, f and g which containing sulfonamide group can detect Hg2+ in the identical condition. It confirmed again that sulfonamide group has high affinity to Hg2+ and is crucial important for the Hg2+ recognition. Because of all d, e, f and g can recognize Hg2+ in aqueous solution: Compound d shows enhancement and blue-shift of fluorescence emission as response to Hg2+ in buffered aqueous solution, but the changes of the fluorescence emission is smaller than a, b and c; f has a similar fluorescence response to Hg2+, which is more weak than d; e and g are quenching the fluorescence emission by Hg2+. It shows that the residue of amino acid is not very important but only assistant for the recognition.In addition, we also in-depth study the function of the BSA in the recognition between dansyl probe and mercury ion. The results showed that BSA in the process of dansyl probe and mercury ion recognition, not only played the role of a platform, but also directly involved in the identification. Firstly, BSA is the host (receptor) of the entire recognition system, and dansyl probe and mercury ion are the guests, and then the two guests interact with each other and induce the fluorescent signal changes. But the dansyl probe and mercury ion need to enter the same or adjacent cavities of the BSA, and can interact with each other in the cavities. So the entire recognition system which contains ternary recognition process is very complicated, and there are mulriple interactions between the three molecules in this system.In conclusion, we have successfully obtained a series sensors for Hg2+ by using sulfonamide as the recognition site and performed in-depth studing of the mechanism, which show a potential guideline in environmental applications oriented toward the chemosensor design and optimization.