Rational design of a lysosomal-targeted ratiometric two-photon fluorescent probe for imaging hydrogen polysulfides in live cells

Abstract Hydrogen polysulfides (H2Sn, n > 1) play important roles in H2S associated physiological functions and pathological processes and H2S2 is regarded to be a newfound potent signal transducer. But fluorescent probes for rapid, sensitive, and selective detecting of H2Sn are still lacking, above all the lysosomal-targeted ones. In this work, by integrating the alkylmorpholine group and 2-fluoro-5-nitrobenzoyl- group into the molecular structure of 1,8-naphthalimide based fluorophore, a new lysosome-targetable ratiometric two-photon fluorescent probe for H2Sn has been designed and synthesized. The probe showed good stability, short response time (5 min), high selectivity and sensitivity (LOD = 10 nM), broad linear range (0–25 μM), admirable two-photon absorption cross sections (Φmax = 324 GM), fine membrane permeability and biocompatibility, and as well as the lysosome targeting ability. Moreover, this work affords a promising approach for detecting and imaging of lysosomal H2Sn, and therefore potentially applied in the study of H2Sn -related biology and pathology.