Synthesis, characterization, and pH-triggered dethreading of α-cyclodextrin-poly(ethylene glycol) polyrotaxanes bearing cleavable endcaps

The synthesis, characterization, and degradation kinetics of three alpha-cyclodextrin (alpha-CD)-poly(ethylene glycol) (PEG) polyrotaxanes with endcaps that were installed using Cu(I)-catalyzed Huisgen cyclization is reported. PEG1500, azidated with azidoacetic acid, was threaded with alpha-CD to form a pseudopolyrotaxane that was then capped in up to 82% yield with three different substituents to provide polyrotaxanes that were either acid-, base-, or fluoride-sensitive. NMR, GPC, XRD, and AFM methods were used to characterize the polyrotaxanes. Dethreading rates upon exposure to mild deprotection conditions were monitored by turbidity analysis. The vinyl ether-endcapped polyrotaxane is stable at pH 7 for 16 h but is solubilized at approximately 0.0211 min(-1) at pH 4. The ester-endcapped polyrotaxane is solubilized at 0.0122 min(-1) at pH 12.1. Our results show that pH-triggerable polyrotaxanes can be readily and efficiently prepared from pseudopolyrotaxanes in high yield by Huisgen cyclization of azido-and alkynyl-modified precursors in the presence of Cu(I).