London Dispersion Modulates Kinetic-Thermodynamic Relationships and Reshapes Reactivity Landscapes

Although London dispersion (LD) is widely recognized to lower the reaction barrier, its influence on kinetic-thermodynamic relationships has remained unrecognized. Here, we systematically investigate how LD affects the set of thermodynamic-independent aspects of reactivity, namely intrinsic barrier (∆G0‡, the reaction barrier for ∆G=0) and Brønsted slope (α, quantifying kinetics sensitivity to thermodynamics ∆∆G‡/∆∆G) across several reaction families, using dispersion energy donors to modulate LD interactions and comparing results from dispersion-uncorrected and dispersion-corrected models. Across multiple systems, LD was found to modulate ∆G0‡ and α appreciably, indicating that its influence is beyond the thermodynamic Bell–Evans–Polanyi behavior. Structural analysis reveals that, in addition to directly shaping the reaction barrier, LD also influences the barrier's responsiveness to driving force through secondary effects, by enabling new non-covalent interactions and geometries along the reaction. By conceptually isolating the thermodynamic-independent consequences of LD, this work reframes dispersion as an active modulator of intrinsic reactivity, enabling clearer distinctions between case-specific and systematic effects, and more confident applications of LD in mechanistic interpretation and reaction design.