Transient diquat inclusion and carboxylate-rim binding to carboxymethyl-α-cyclodextrin: a molecular dynamics study

In all-atom explicit-water simulations, diquat binding to carboxymethyl-α-cyclodextrin is dominated by dynamic carboxylate-rim contacts, with only 5 of 802 guest-frame pairs showing cavity-cylinder inclusion.

• Why it matters: Rotaxane scavengers for diquat detoxification depend on whether binding comes from cavity inclusion or rim interactions, which has been unclear and affects how such systems should be designed.
• What they did: All-atom molecular dynamics ran for ~4.5 s across five CM–CD systems (neutral pH 3, hexaanionic pH 10, an inclusion complex, and two pseudopolyrotaxanes), with 1.2 s unbiased sampling for the hexaanionic host-guest case.
• The result: A relaxed threaded geometry formed briefly (0.03 nm from the cavity axis; 9 of 14 heavy atoms in the cavity cylinder), but the guest left within 50 ps and stayed mainly at the rim; rim contacts averaged 3.8–4.4 host heavy-atom contacts per frame, while neutral-host interactions were substantially reduced.

AI summary of the abstract · may contain errors · not medical advice · read the paper.