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

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.