Accelerating or Slowing: Fine Tuning the De-Threading Kinetics of a T-Shaped Benzimidazolium Pumping Cassette

Artificial molecular machines (AMMs) rely on precise control of molecular motion, often enabled by mechanically interpenetrated architectures such as pseudorotaxanes. Here, we systematically investigated a library of [2]pseudorotaxanes formed by the combination of T-shaped benzimidazolium threads featuring variable stopper sizes and crown ether wheels (24C6, B24C6, and 23C6), to elucidate how structural parameters govern [2]pseudorotaxane stability and de-threading kinetics. Using ring-closing metathesis and subsequent hydrogenation, we synthesized 10 neutral [2]pseudorotaxanes in high yields (76-87%). Kinetic studies in DMSO-d₆ at 338 K revealed that de-threading half-lives (t₁_/₂) span five orders of magnitude, from 0.237 hours (3a⁻, ΔG^‡ = 24.63 kcal/mol) to 436 hours (5c⁻, ΔG^‡ = 31.87 kcal/mol). Notably, stopper enlargement and macrocycle rigidification (eg., via B24C6) significantly suppressed de-threading rates; 4d⁻, bearing a benzylic phenyl stopper and B24C6, showed a ΔG^‡ of 29.04 kcal/mol and a t₁_/₂ of 168 hours. Gas-phase modeling and NMR analyses further elucidated the roles of stopper geometry and host-guest interactions in modulating energy barriers. These findings provide design principles for the construction of pseudorotaxane-based modules, paving the way for programmable molecular pumps and advanced AMMs.