In summary, the HPLC studies showed that reductive release is fast and operates by 5-exo-trig cyclisation according to the proposed mechanism; that deselenisation is not a complicating factor; and indicated that on-reductant cyclisation may be speedy (G1) or absent (RX1). As on-reductant cyclisation can be key for probes to resist (RX1), or succumb to (G1), monothiol-exchange-based triggering, we expected this to determine their reduction selectivity in cells.