Chemiluminescent probes for imaging H₂S in living animals

Abstract

Hydrogen sulphide (H₂S) is an endogenous mediator of human health and disease, but precise measurement in living cells and animals remains a considerable challenge. We report the total chemical synthesis and characterization of three 1,2-dioxetane chemiluminescent reaction-based H₂S probes, <b>CHS-1, CHS-2</b>, and <b>CHS-3.</b> Upon treatment with H₂S at physiological pH, these probes display instantaneous light emission that is sustained for over an hour with high selectivity against other reactive sulphur, oxygen, and nitrogen species. Analysis of the phenol/phenolate equilibrium and atomic charges has provided a generally applicable predictive model to design improved chemiluminescent probes. The utility of these chemiluminescent reagents was demonstrated by applying <b>CHS-3</b> to detect cellularly generated H₂S using a multi-well plate reader and to image H₂S in living mice using CCD camera technology.