Much faster tribofilm growth has been observed for ZDDPs with secondary alkyl substituents compared to primary ones in macroscale tribometer experiments under both mixed/boundary (load mostly supported by the solid asperities) and full-film elastohydrodynamic lubrication (EHL) (load supported by the pressurized lubricating fluid) conditions, which has been rationalised by the greater stability of the carbocation formed during C-O cleavage in the former. Since the initial C-O cleavage reaction is the rate-determining step for ZDDP tribofilm formation, this bond is probably the key mechanophore for this process. Although shear stress controls the rate of tribofilm formation at the macroscale, at the molecular level it is likely that the rate of C-O cleavage is accelerated by tensile stress. The structure and position of the chemical groups surrounding the mechanophore is known to influence the reactivity of mechanochemical processes. For example, in polymer mechanochemistry, longer chains are known to lead to enhanced reactivity in both bulk liquid flows and solid grinding experiments. Single-molecule force spectroscopy experiments have shown how the 'lever-arm effect' can enhance mechanochemical reactivity by polymer backbones acting as phenomenological levers that impose greater mechanical distortion on the mechanophore. Cyclopropane-based polymers containing E-alkenes showed activation lengths (force-dependent equivalent of the stress-dependent activation volume) that were a third larger than those containing Z-alkenes. Substituent effects can differ depending on the reaction pathway; for example, cyclobutene-based polymers containing trans-alkyl handles provided more mechanical leverage than trans-ester handles in conrotatory reactions, whereas cis-ester handles gave more mechanical leverage than cis-alkyl handles in disrotatory reactions. The enhanced mechanical leverage of dialkyl relative to diester attachments was consistent with quantum chemical calculations reported previously on trans-cyclobutene derivatives. In similar polymers, replacing a methylene in the pulling attachment with a phenyl group dropped the force necessary to achieve a given rate constant in SMFS experiments by a factor of three, which was attributed to a combination of electronic stabilization and mechanical leverage effects. More conventional substituent effects that can be explained through linear free energy relationships, have also been identified using SMFS. For example, spiropyran-derived polymers containing more electron-withdrawing substituents in the para position to the labile spirocyclic C-O bond required less force to break. Substituent effects have also been predicted for small molecules from quantum chemical calculations; however, to our knowledge, substituent effects such as the lever arm effect are yet to be detected experimentally for molecular or organometallic systems, such as ZDDP.