One-Pot Route To Nanocontainer

In a stroke of serendipity, chemists at Rutgers University have discovered a one-pot reaction in which 18 molecular components react sequentially to form, in high yield, a cavernous, covalent molecule that potentially could encapsulate other, smaller molecules (Angew. Chem. Int. Ed., published online Dec. 30, 2005, dx.doi.org/10.1002/anie.200504049).

Although a couple of covalent "nanocontainer" molecules have been synthesized previously, the new route is operationally far more efficient, and it also is atom-efficient. These features could be advantageous in potential applications such as drug delivery, separation science, catalysis, and sensing.

Peer reviewers of the paper, authored by Ralf Warmuth and coworkers, have been enthusiastic, calling it "elegant," "very impressive," and "spectacular." "This work will be a cornerstone in the development of covalent nanocontainers," one reviewer writes.

Warmuth's nanocontainer is an octahedral structure assembled from six bowl-shaped molecules called cavitands and 12 ethylene-1,2-diamine linkers. Each cavitand has four formyl groups on its rim, and these react with the 24 amino groups of the linkers to form 24 imine bonds.

This condensation is so efficient, Warmuth explains, because the imine bonds form reversibly, "allowing for error correction and ultimately furnishing the thermodynamically most stable product." Once the condensation is complete, the imine bonds are reduced with sodium borohydride so that the octahedral compound can be isolated in 63% yield and purified.

The Rutgers team, which includes Xuejun Liu, Yong Liu, and Gina Li, finds that the solvent is a key factor controlling the shape of the nanocontainer. Chloroform is the best solvent for making the octahedral assembly (a hexamer), and other solvents preferentially lead to formation of the octamer or the tetramer, according to Warmuth.

Last year, Darren A. Makeiff and John C. Sherman of the University of British Columbia, Vancouver, reported a related six-cavitand molecular vessel that entraps seven guest molecules (J. Am. Chem. Soc. 2005, 127, 12363). That synthesis involved four steps.

Warmuth's octahedral nanocontainer has an inner cavity of about 1,700 ų, which he says is large enough to encapsulate two or three buckyballs (C₆₀ molecules). Thus far, however, he and his coworkers haven't demonstrated that their nanocontainer can trap or slowly release any guest molecules, such as drugs. Those experiments are now in progress, Warmuth tells C&EN.