Analysing reductive release pathways identified four key design aspects, which convinced us that probes based on a desymmetrised cyclic selenenylsulfide trigger A represent a unique TrxR-selective solution (Fig. ; see also Fig. and Supporting Note 3). It also suggested that the thermodynamically identical regioisomers G (Fig. ) ought not be TrxR-selective, so giving highly stringent controls for our postulated specificity mechanism: