Understanding SO₂ Reactivity with the NBD-Piperazine Motifs Commonly Used in H₂S Detection and Elimination: Kinetic...

Thiolysis of nitrobenzooxadizole (NBD)-piperazine motifs has been widely utilized for the development of hydrogen sulfide (H₂S) probes and scavengers. Despite this prevalence, the selectivity of this important reaction remains underscrutinized because some NBD-based probes showed a certain fluorescence response toward sulfur dioxide (SO₂). Herein, we present experimental and computational investigations for a deeper understanding of SO₂ reactivity with different NBD-piperazine motifs and uncover new chemistries. We demonstrate that the reaction rates of SO₂ with NBD piperazines are 2 orders of magnitude slower than those of H₂S, thus underscoring high selectivity of the NBD-piperazine motifs for the development of H₂S scavengers. We demonstrate that the incorporation of a positively charged group onto the NBD-piperazine motifs promotes fast and reversible formation of an NBD/SO₂ supramolecular complex with a moderate binding constant. In addition, the positively charged microenvironment from cationic micelles also promotes the binding of NBD probes with SO₂, resulting in a fluorescence response that may interfere in H₂S detection. To address this limitation, we rationally designed a dual-NBD-caged probe to selectively sense H₂S over SO₂ and provided the first quantitative illustration of the improved selectivity for such a dual-caged strategy. Our work should offer valuable insights into the development of highly selective tools for reactive sulfur research.