In contrast, exchange of regioisomer G to give K does allow the thiol intermediate to undergo fast 5-exo-trig cyclisation, permitting "on-reductant release" (krel-K) without full reduction to J. Therefore, although the thermodynamics and kinetics of overall reduction of the trigger motifs of A and G are likely to be almost indistinguishable, we expect that probes of type G will suffer significantly more unwanted cargo release after unavoidable initial exchange with the monothiol background. (Though H can also give on-protein release krel-H, full reduction to J by the preorganised TrxR is likely to be much faster than cyclisation, so we expect the krel-H pathway to play little role in TrxR-based cargo release: see section "Oxidoreductase profiling").