To systematically create all possible products, we create a set of all conversion matrices. However, to avoid a computational explosion and to make it more likely that the product is connected to the reactant by a single TS, we constrain the maximum number of bond dissociations and formations to three, respectively. In other works , the same type of maximal bond formation/dissociation constraints have been used, but are set to two instead. We choose three bond changes because reaction 2 in Figure cannot be obtained using two bond changes. We also constrain the chemical distance (CD) between the reactant and product to 5 bind changes, that is: