Additionally, it is important to recognize that there is a trade-off when using higher-order reaction class schemes in the IDR approach. As we climb the RC scheme ladder, reference molecules in the constructed reactions tend to more closely resemble the target species due to the added constraints. This increased similarity between the reference and target species generally leads to better error cancelation, for the systematic errors associated with computational chemistry calculations or experiments are more likely to cancel out for reactants and products that share similar chemical environments in constructed isodemic reactions.