Development of Selective Colorimetric Probes for Hydrogen Sulfide Based on Nucleophilic Aromatic Substitution

Abstract

Hydrogen sulfide is an important biological signalling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated sub-micromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications.

A FRET-based ratiometric fluorescent probe for visualizing H2S in lysosomes

“…After the reaction, the red shift of the peak at 480 nm was due to the thiolysis of NBD amine to result NBD-SH, while the decrease of the absorbance around 530 nm was attributed to the disulfide linkage of NBD-SH. 13 The response of the probe towards H 2 S could also be observed by naked eye (Fig. 2 inset).…”

“…The resulted residue was purified by silica gel column chromatography (MeOH:CH 2 Cl 2 ¼1.5%) to give colorless oil 6 (36 mg, 90%). TLC (silica plate): R f ¼0.3 J¼13.3, 6.6 Hz, 1H), 1.44 (s, 9H) 13. C NMR (101 MHz, CDCl 3 ) d 164.2,…”

Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems

“…118 The Pluth group has previously reported selective probes for colorimetric assays using the NBD scaffold. 44 Recently, Pluth and coworkers have expanded upon their mechanistic studies to develop a fluorescent NBD-coumarin probe 51 that would display different emission profiles in the presence of H 2 S or biothiols, allowing for spectral differentiation of these species. 119 …”

A BODIPY-based turn-on fluorescent probe for the selective detection of hydrogen sulfide in solution and in cells

“…2 As expected, the reaction of Na 2 S with probe 1 triggered the cleavage of NBD ether bond and a green fluorescent BODIPY 1 was released (Scheme 1). The changes in absorption and emission spectra of probe 1 in the presence of Na 2 S were reasonably ascribed to the formation of BODIPY 1 and NBD-SH, for an authentic sample of BODIPY 1 showed the same maximum absorption band at 500 nm and emission band centered at 510 nm, and nonfluorescent NBD-SH exhibited a major absorption band centered at 530 nm [50]. The proposed sensing mechanism was also proved by mass spectrometry of the reaction mixtures, the peak at m/z 339.2 [MH]  assigned to BODIPY 1 was clearly observed (Fig.…”