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Manipulating Single Molecules in an Atomically Sharpened Nanotube

C. Gao and L.Q. Gu
University of Missouri, US

nanotube, Enantio-separation, single molecules,

Ultra-sensitive detections at the single molecule level can be used to dissect dynamic molecular processes, such as structure-correlated enzymology1, powered motor movement2, molecular folding3, and bio-transportation4-6. One of central challenges among various single molecule methods is precise molecular manipulation7-9. Here we report a lab-in-hand, portable silica nanotube which possesses a unique wineglass-shaped nanocavity with a dimension that can be chemically tuned at sub-nanometer level. It is striking to find that a single molecule of cyclodextrin (1.5 nm) can be permanently inlaid to the wineglass cavity of an appropriate-sized nanotube in the presence of electroosmotic drive. With this nanotube, we have successfully observed at the single molecule level the host-guest interactions between trapped cyclodextrin and a series of enantiomeric pharmaceuticals. Stochastic kinetics clearly revealed a chirality-polarity-coupled “catalytic” encapsulation mechanism, by which the R-form guest containing high polarity group at the chiral center overrides lower energy barrier than its S-form enantiomer when interacting with cyclodextrin. This finding leads to a sensitive single molecule method of enantio-descrimination for drug discovery. The robust molecular manipulation method in this report may have broad impacts for molecular reactions, single molecule delivery, patterning and sensing.

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