How London Dispersion Affects Intrinsic Reactivity

London dispersion (LD) interactions are increasingly recognized as key contributors to reactivity and selectivity in organic and catalytic processes. While their barrier-lowering effects are typically attributed to thermodynamic stabilization that pulls down the reaction barrier, whether LD also affects how sensitively reaction barriers respond to changes in thermodynamic driving force has not previously been recognized or examined. Here, we systematically investigate how LD affects the set of thermodynamic-independent aspects of reactivity, namely intrinsic barrier (∆G0‡) and Brønsted slope (α) across several reaction families, using dispersion energy donors to modulate LD interactions and comparing results from dispersion-uncorrected (B3LYP) and dispersion-corrected (B3LYP-D3BJ) models. Across multiple systems, including [3+2] and [4+1] cycloadditions, LD was found to modulate ∆G0‡ and α appreciably, indicating that its influence extends 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 distinction between case-specific and systematic effects, and more confident application of LD in mechanistic interpretation and design.