Off-label use of old drug: A 3-hydroxythalidomide-based fluorescent probe for the detection of hydrogen sulfide (H2S) and bioimaging in HeLa cells

Abstract Hydrogen sulfide (H2S) had critical physiological functions as the third gasotransmitter in the living system, along with nitric oxide and carbon monoxide. In this work, based on the known metabolic pathway of thalidomide and its binding style to cereblon protein, we designed and synthesized a colorimetric turn-on fluorescent probe (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)2,4-dinitrobenzenesulfonate for the detection of H2S in living cells. Upon the addition of NaHS solution (as H2S donor), the fluorophore was released by the nucleophilic reaction, and the fluorescent intensity at 495 nm increased linearly as a function of H2S concentration (regression factor, R2 = 0.998) with a LOD of 6.4 nM. The sensing mechanism was confirmed by 1H NMR titration and DFT calculations. Furthermore, the probe showed high selectivity and sensitivity for H2S over GSH and other analytes, and it was successfully applied in the detection of sophisticated oilfield sewage and bioimaging in HeLa cells.