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

Hydrogen sulfide is an important
biological signaling 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 submicromolar
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.

硫化氢（Hydrogen sulfide）是一类重要的生物信号分子，同时也是检测领域的关键环境靶标。开发硫化氢检测方法的核心挑战之一，在于如何区分硫化氢与硫醇及其他亲核试剂（nucleophiles）高度相似的反应活性。为解决这一需求，研究人员开发出以硫化氢与缺电子芳香亲电试剂发生亲核芳香取代反应（nucleophilic aromatic substitution, SNAr）为核心的策略，以实现硫化氢与硫醇反应活性的分离。将硝基苯并呋咱（nitrobenzofurazan）硫醚——即7-硝基-1,2,3-苯并恶二唑（7-nitro-1,2,3-benzoxadiazole, NBD）硫醚——的水溶液与硫化氢反应时，会发生硫醇消去反应，生成硝基苯并呋咱硫醇，其最大吸收波长λmax为534 nm。该反应特性可使原本生成的副产物硫醚，在与硫化氢反应后转化为目标产物硝基苯并呋咱硫醇。通过哈米特线性自由能关系研究对该反应的底物适用范围进行了考察，所得ρ值为+0.34，与所提出的SN2Ar反应机理相一致。所开发的探针在缓冲液与血清中均展现出优异的检测效能，其亚摩尔级检测限低至190 nM（缓冲液体系）与380 nM（血清体系）。此外，硝基苯并呋咱亲电试剂与硫化氢反应呈现的S型响应曲线可通过拟合实现硫化氢的准确定量。该检测策略为硫化氢检测提供了全新的技术路径，我们预计其将在未来诸多应用场景中得到推广。