The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, activation energies are the sum of the energies to distort reactants into transition state geometries and the interaction energies between the distorted molecules. The energy required to distort molecules is called activation strain or distortion energy, which is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by stabilizing interaction energy. Analyzing changes in these energies along the reaction coordinate provides insights into factors controlling reactivity. This model has been applied to various reactions in organic and inorganic chemistry, including substitutions, eliminations, cycloadditions, and organometallic reactions. The model, developed by Bickelhaupt and Houk, extends the original FMO model by considering distortion and interaction energies. It accounts for reactions that do not conform to symmetry principles and explains how reaction barriers depend on the balance between distortion and interaction energies. The model decomposes the potential energy surface into distortion energy (associated with structural changes) and interaction energy (between distorted molecules). The activation strain model provides a systematic way to analyze reaction barriers by decomposing the energy into these two components. The model has been applied to various reactions, including E2 and S_N2 reactions, where it explains how the activation barrier depends on the stability of the interaction and the distortion energy. For example, a better nucleophile lowers the S_N2 barrier by enhancing the stabilizing interaction, while a poorer leaving group raises the barrier due to increased strain. The model also explains the regioselectivity in cycloadditions and other pericyclic reactions, showing how the interaction and distortion energies influence the reaction pathway. In homogeneous catalysis, the model explains how the bite angle of metal-ligand complexes affects the activation energy of bond activation. A smaller bite angle reduces the activation barrier by decreasing the strain energy. The model has also been applied to bioorthogonal reactions, where it explains how the reactivity of cycloaddends depends on their distortion and interaction energies. Overall, the activation strain/distortion/interaction model provides a comprehensive framework for understanding reaction barriers and reactivity trends in various chemical processes. It has been successfully applied to a wide range of reactions, offering insights into the factors that control reaction rates and selectivities.The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, activation energies are the sum of the energies to distort reactants into transition state geometries and the interaction energies between the distorted molecules. The energy required to distort molecules is called activation strain or distortion energy, which is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by stabilizing interaction energy. Analyzing changes in these energies along the reaction coordinate provides insights into factors controlling reactivity. This model has been applied to various reactions in organic and inorganic chemistry, including substitutions, eliminations, cycloadditions, and organometallic reactions. The model, developed by Bickelhaupt and Houk, extends the original FMO model by considering distortion and interaction energies. It accounts for reactions that do not conform to symmetry principles and explains how reaction barriers depend on the balance between distortion and interaction energies. The model decomposes the potential energy surface into distortion energy (associated with structural changes) and interaction energy (between distorted molecules). The activation strain model provides a systematic way to analyze reaction barriers by decomposing the energy into these two components. The model has been applied to various reactions, including E2 and S_N2 reactions, where it explains how the activation barrier depends on the stability of the interaction and the distortion energy. For example, a better nucleophile lowers the S_N2 barrier by enhancing the stabilizing interaction, while a poorer leaving group raises the barrier due to increased strain. The model also explains the regioselectivity in cycloadditions and other pericyclic reactions, showing how the interaction and distortion energies influence the reaction pathway. In homogeneous catalysis, the model explains how the bite angle of metal-ligand complexes affects the activation energy of bond activation. A smaller bite angle reduces the activation barrier by decreasing the strain energy. The model has also been applied to bioorthogonal reactions, where it explains how the reactivity of cycloaddends depends on their distortion and interaction energies. Overall, the activation strain/distortion/interaction model provides a comprehensive framework for understanding reaction barriers and reactivity trends in various chemical processes. It has been successfully applied to a wide range of reactions, offering insights into the factors that control reaction rates and selectivities.