A thermodynamically unfavorable reaction can proceed as part of a larger favorable process when reactions are coupled through a shared molecular mechanism.

Suppose

$$\mathrm{A\rightarrow B}$$

has

$$\Delta G_1>0,$$

while

$$\mathrm{C\rightarrow D}$$

has a sufficiently negative

$$\Delta G_2<0.$$

If the chemistry is linked so that the two transformations occur as one net process,

$$\mathrm{A+C\rightarrow B+D},$$

the reaction Gibbs energies add:

$$\boxed{\Delta G_{\rm total}=\Delta G_1+\Delta G_2}.$$

If $\Delta G_{\rm total}<0$, the combined forward process is thermodynamically favorable under those conditions.

Example

If

$$\Delta G_1=+12,\mathrm{kJ/mol}$$

and

$$\Delta G_2=-30,\mathrm{kJ/mol},$$

then

$$\Delta G_{\rm total}=-18,\mathrm{kJ/mol}.$$

The favorable second transformation can therefore provide the thermodynamic driving force for the combined process.

Coupling requires chemistry, not proximity

Simply placing two unrelated reactions in the same container does not make one drive the other. There must be a shared intermediate, transferred chemical group or other molecular connection that makes progress of one transformation contingent on progress of the other.

For example, instead of trying to drive

$$\mathrm{A\rightarrow B}$$

directly, a favorable reaction might first convert A into a more reactive intermediate $\mathrm{A^*}$:

$$\mathrm{A+C\rightarrow A^*+D},$$

followed by

$$\mathrm{A^*\rightarrow B}.$$

Adding the two transformations cancels the intermediate $\mathrm{A^*}$ and gives the coupled net reaction.

Thermodynamic favorability still does not specify how rapidly the process occurs. The reaction mechanism must provide an actual pathway between the coupled states.

Group-transfer reactions and many biosynthetic or transport processes are applications of this general principle. The important idea is not the identity of a particular energy carrier: coupling works because linked reactions form one thermodynamic process whose free-energy changes add.