1. Perturbation of chemical exchange through coupling to a chemostated spontaneous process. Using trajectory thermodynamics 13e it is possible to formally demonstrate that "coupling" a simple chemical exchange A B, to a general spontaneous process can lead to a non-equilibrium steady state in which concentrations [A] and [B] do not conform to KAB (see ESI). To demonstrate how such coupling can arise in a real system we consider the exchange between RCO2Me and RCO2 - coupled to the alkaline hydrolysis of MeI (Figure ). For simplicity, we consider the outcome if [MeI], [OH], [MeOH] and [I] (the components of the MeI hydrolysis reaction) are held at fixed values (chemostated). Trajectory thermodynamics can be used to generate an expression (Figure , eq. 1) for the relationship between [RCO2Me] and [RCO2] 15 at steady state if chemically unphysical steps are discounted (see ESI). The same expression is reached (see ESI) if we consider a network that includes all processes that exchange RCO2 -and RCO2Me (Figure ).