Simultaneous detection of small molecule thiols with a simple ¹⁹F NMR platform

Thiols play critical roles in regulating biological functions and have wide applications in pharmaceutical and biomedical industries. However, we still lack a general approach for the simultaneous detection of various thiols, especially in complex systems. Herein, we establish a ¹⁹F NMR platform where thiols are selectively fused into a novelly designed fluorinated receptor that has two sets of environmentally different ¹⁹F atoms with fast kinetics (k ₂ = 0.73 mM^-1 min^-1), allowing us to generate unique two-dimensional codes for about 20 thiols. We demonstrate the feasibility of the approach by reliably quantifying thiol drug content in tablets, discriminating thiols in living cells, and for the first time monitoring the thiol related metabolism pathway at the atomic level. Moreover, the method can be easily extended to detect the activity of thiol related enzymes such as γ-glutamyl transpeptidase. We envision that the versatile platform will be a useful tool for detecting thiols and elucidating thiol-related processes in complex systems.