Enthalpy-Entropy Compensation in Chemical Kinetics

Enthalpy-entropy compensation describes a systematic linear correlation between changes in activation enthalpy (ΔH‡) and activation entropy (ΔS‡) observed across series of related chemical reactions. Within transition state theory, both parameters define the free energy barrier (ΔG‡) governing reaction rates; compensation emerges when reductions in ΔH‡ are offset by decreases in ΔS‡ (or vice versa), yielding a relatively constant ΔG‡. This interplay often reflects alterations in solvation, structural reorganisation or substituent effects that modify the degree of order between ground state and transition state ensembles. The concept has been applied to diverse systems—from unimolecular thermal decompositions to bimolecular nucleophilic substitutions and enzyme‐catalysed transformations—offering mechanistic insight into how subtle changes in reaction environment influence rate constants. Recognition of compensation phenomena guides the rational design of catalysts and solvents by indicating whether enthalpic stabilisation of a transition state may be nullified by entropic penalties, and vice versa. It also underpins isokinetic relationships, where families of reactions converge at a characteristic “isokinetic temperature” at which rate constants become invariant to structural perturbations. Understanding enthalpy-entropy compensation thus remains pivotal for predicting kinetics, optimising catalytic efficiency and interpreting structure–reactivity trends in both homogeneous and heterogeneous chemical systems.

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Enthalpy-Entropy Compensation in Chemical Kinetics publication trend

The graph below shows the total number of articles in enthalpy-entropy compensation in chemical kinetics across all publications each year (not limited to Nature Index journals).

Technical terms

Enthalpy-entropy compensation: A linear correlation between activation enthalpy and activation entropy changes that yields a near-constant activation free energy across related reactions.

Activation enthalpy (ΔH‡): The enthalpic component of the energy barrier that must be overcome for reactants to reach the transition state.

Activation entropy (ΔS‡): The entropic component reflecting changes in disorder or degrees of freedom when forming the transition state from reactants.

Isokinetic relationship: A phenomenon where a series of reactions with different substituents exhibit identical rate constants at a specific temperature where enthalpy-entropy compensation holds exactly.

Transition state theory: A framework describing chemical reaction rates in terms of an activated complex whose free energy relative to reactants determines the rate constant.

References

1. Реакційна здатність пропілових естерів 2-(бензоїламіно)(1-R-оксоіндолін-3-іліден)оцтових кислот. Journal of organic and pharmaceutical chemistry (2019).
2. Substituent Effects on the Activation Parameter Changes for the Aminolysis in the Bimolecular Nucleophilic Reactions in Solution. Journal of Applied Solution Chemistry and Modeling (2014).
3. Solvent and Substituent Effects on the Kinetics of Thermolysis of cis-Fused 1,2,4-Trioxanes. Molecules (2001).