(3): A should avoid cargo release before reduction, and so have monothiol resistance: The E° values for the intermediates can be compared to the ca. -364 mV for intact cyclic selenenylsulfide triggers from Iwaoka's elegant study (Fig. ). Thus, the stability of linear diselenide intermediates B and H (from TrxR selenol attack; -550 mV) better offsets the energetic penalty of opening the cyclic selenenylsulfide, than can linear selenenylsulfide intermediates D and K (from thiol attack; ca. -280 mV). Thus, attack by TrxR should be much more thermodynamically favoured than by thiols.