The cross second-derivative of the activation energy,${ heta}$G${ eq}$ , with respect to the two component thermodynamic barriers, ${ heta}$G˚X and ${ heta}$G$^{circ}C$Y, can be given in terms of a cross-interaction constant (CIC), $etaXY( hoXY)$, and also in terms of the intrinsic barrier,${ heta}$G${ eq}$ , with a simple relationship between the two: $etaXY$ = $-1}(6${ heta}$G${ eq}$).$</TEX> This equation shows that the distance between the two reactants in the adduct (TS, intermediate, or product) is inversely related to the intrinsic barrier. An important corollary is that the Ritchie N+ equation holds (for which $etaXY$ = 0) for the reactions with high intrinsic barrier. Various experimental and theoretical examples are presented to show the validity of the relationship, and the mechanistic implications are discussed.