Substituting n3 for 2-Nocc in eq 3 leads to a remarkably accurate prediction of reactivity (Figure ). Specifically, each three-membered ring fused to the breaking C-C bond reduces the intrinsic activation energy by ~10 kcal mol -1 , corresponding to a ~10 7 -fold increase in the rate constant at 298 K. As noted above, this simple model effectively captures the greater reactivity of cyclopropane over cyclobutane, and also the contrasting reactivities of [1.1.1]propellane and cyclopropane; the increased reactivity of the former can be attributed to a greater number of three-membered rings fused to the breaking bond (n3 = 3). Varying the number of three-membered rings fused to a breaking bond therefore offers a simple way to modulate the reactivity of the system -for example, switching the behavior of a molecule from a highly-reactive bioconjugation warhead (e.g., bicyclo[1.1.0]butanes similar to D) to an inert lipid tail group (e.g. bicyclo[2.2.0]hexane 'ladderanes' based on G). We recently applied this concept to develop the radical ring-opening reactivity of [3.1.1]propellane (J). Compared with [1.1.1]propellane, [3.1.1]propellane sacrifices bond delocalization (n3 = 3 vs 2, respectively) in exchange for an increased driving force (∆Hr = -28.2 vs -42.1kcal mol -1 , respectively, Figure ). The predicted difference in ∆H ‡ between these systems for a radical addition is 3.8 kcal mol -1 , in good agreement with the calculated value of 1.1 kcal mol -1 (krel,calc ~ 0.2 at 298 K). This result suggests that the antagonistic effect of decreasing delocalization but increasing strain release coincidentally results in similar radical reactivity to [1.1.1]propellane. Pleasingly, [3.1.1]propellane was found to be a viable substrate for numerous radical reactions previously developed for [1.1.1]propellane, including atom transfer radical additions, dual photoredox/Cu catalysis, and chalcogen atom addition reactions. The delocalization model (eq 4) can also be applied to two-electron processes, such as the nucleophilic addition of amide anions to D, E and H. When using NH2 -as a model nucleophile, an excellent correlation and low error was observed between predicted and calculated activation enthalpies (R 2 = 0.98, RMSE = 2.7 kcal mol -1 , Figure ). The 𝛽 coefficient (-10.4 kcal mol -1 ) is almost identical to the one-electron reaction, which supports the idea that delocalization-modulated reactivity is intrinsic to the bonding pattern found in the small rings. If delocalization effects were absent, the barrier to nucleophilic addition to [1.1.1]propellane would increase by ~30 kcal mol -1 , rendering it inert under the reaction conditions. In other words, strain release alone cannot account for the observed reactivity -delocalization again emerges as the primary driver of reactivity. This same principle holds true for bicyclo[1.1.0]butanes (D) and bicyclo[2.1.0]pentanes (housanes, E),