Broadening the Toolbox in Drug Development and Analysis - Pharmaceutical Technology

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Broadening the Toolbox in Drug Development and Analysis
Some recent advances involve strategies for accelerating reaction discovery, approaches for inducing chirality and stereochemical analysis, and applications in nanotechnology for protein elucidation.


Pharmaceutical Technology
Volume 36, Issue 1, pp. 52-56

Applications in nanotechnology

Interdisciplinary approaches in chemistry, biology, polymer science, and the new sciences, such as nanotechnology, are important in advancing drug development and drug delivery. Researchers at the University at Buffalo have synthesized tiny, molecular cages that can be used to capture and purify nanomaterials. The traps are derived from a special kind of molecule, so-called a "bottle-brush molecule," which consists of small organic tubes whose interior walls carry a negative charge. This feature enables the tubes to selectively encapsulate only positively charged particles, according to a Dec. 5, 2011, University of Buffalo press release. The researchers reported on the new method for fabricating amphiphilic organic nanotubes from multicomponent bottlebrush copolymers with triblock terpolymer side chains. The obtained nanotubes were highly selective carriers for positively charged molecules and nanometer-size macromolecules by means of liquid–liquid extractions. The researchers were able to discriminate between dendrimers with about 2 nm size differentials (5). These kinds of cages could be used, in the future, to expedite tasks, such as segregating large quantum dots from small quantum dots or separating proteins by size and charge.

"The shapes and sizes of molecules and nanomaterials dictate their utility for desired applications," said Javid Rzayev, assistant professor of chemistry at the University of Buffalo and co-author of the study, in the university release. "Our molecular cages will allow one to separate particles and molecules with predetermined dimensions, thus creating uniform building blocks for the fabrication of advanced materials."

To create the traps, Rzayev and his team first constructed a special kind of molecule called a bottle-brush molecule. These resemble a round hair brush, with molecular "bristles" protruding all the way around a molecular backbone, according to the university release. After stitching the bristles together, the researchers hollowed out the center of each bottle-brush molecule, leaving behind a tube-like structure. When building the bottlebrush molecules, the scientists constructed each molecule using molecular structures that disintegrate upon coming into contact with water and around this core, attached a layer of negatively charged carboxylic acid groups. To design the molecule, the scientists immersed it water, in effect hollowing the core. The resulting structure was the trap, a nanotube whose inner walls were negatively charged due to the presence of the newly exposed carboxylic acid groups, according to the university release.

To test the tubes' effectiveness as traps, the researchers designed a series of experiments involving a two-layered chemical cocktail, according to the university release. The bottom layers consisted of a chloroform solution containing the nanotubes, and the top layer consisted of a water-based solution containing positively charged dyes. After shaking, the nanotubes collided with and trapped the dyes, bringing the dyes into the chloroform solution. In similar experiments, the researchers used the nanotubes to extract dendrimers from an aqueous solution. The nanotubes were designed so that dendrimers with a diameter of 2.8 nm were trapped, and dendrimers that were 4.3 nm across were left in solution. To remove the captured dendrimers from the nanotubes, the researchers lowered the pH of the chloroform solution, which shut down the negative charge inside the traps and allows the captured particles to be released from their cages, according to the university release.

References

1. A. McNally, C.K. Prier, and D.W.C. MacMillan Science 334 (6059), 1114–1117 (2011).

2. D.A. Nicewicz and D.W.C. MacMillan, Science 322 (5898) 77–80 (2008).

3. C. Rosenblatt et al., Phys. Rev. Lett. 107 (23), 237804–7808 (2011).

4. R.R. Gil et al., ACS Nano 5 (11), 8935–8942 (2011).

5. J. Rzayev and K. Huang, J. Am. Chem. Soc. 133 (42), 16726–16729 (2011).

Patricia Van Arnum is a executive editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072,
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