Published online 12 August 2008 | Nature | doi:10.1038/news.2008.1028

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Molecules multiplied

Synthetic chemists hope to apply the power of PCR to a range of other compounds.

Chemists have developed a way to produce vast numbers of organic molecules from trace amounts, by triggering a reaction that selectively makes the same molecule over and over again.

flasksThe molecular amplifier can make the same molecule over and over and over and over ...Punchstock

The ability to amplify minuscule quantities of DNA into workable samples, using the polymerase chain reaction (PCR), has transformed biology. Now Chad Mirkin and Hyo Jae Yoon at Northwestern University in Evanston, Illinois, think they have a working example that proves that the feat is possible for compounds other than nucleic acids.

The technique could be the basis of an ultrasensitive detection method, Mirkin says. Such processes could allow tiny amounts of explosives or biological contaminants to be picked out, amplified and identified.

Jeremy Sanders, a chemist at the University of Cambridge, UK, says that synthetic chemists would love to be able to apply the power of PCR to other molecules. And although mass spectrometry is often used to detect tiny traces of molecules, it can't work at the single-molecule level, says Sanders – something that, in principle, Mirkin's system can achieve.

Chemical amplifier

Mirkin's demonstration process makes the acetate anion from two other organic molecules: acetic anhydride and pyridyl carbinol.

At the heart of his chemical amplifier is a molecular factory, containing a pair of carbon-based salen molecules, each of which is stuck to a zinc atom. Together, they act as a catalyst to speed up the reaction that makes acetate.

But these zinc-salen units are held together by flexible groups containing rhodium metal. These normally adopt a 'closed' position that holds the salen groups together, shutting down their activity.

That all changes when a trace amount of acetate is added to the mix. The rhodium atoms recognise and bind to the acetate, shifting their bonds as they do so and opening up the molecular factory to create a catalytic cavity between the two zinc-salen groups.

As reactants squeeze through the cavity, they create acetate molecules. This acetate goes on to activate more catalysts, producing yet more acetate at an exponential rate until virtually all of the reactants are used up. The system is reported in the Journal of the American Chemical Society1.

Lots of tinkering

There are many existing examples of autocatalytic reactions, where the product helps to speed up its own production. Mirkin's system is different, however, because the acetate product is merely responsible for activating the catalyst, rather than acting directly as a catalyst itself.

This potentially makes the system much more adaptable to different molecules, says Stephen Craig, a chemist at Duke University in Durham, North Carolina, who works on self-replicating systems. "The design makes use of fairly simple and well understood coordination chemistry," he says. Sanders adds that the work is promising, but that it is still a long way from being a true analogue of PCR.

Mirkin is now working on catalytic systems that have an active site containing just one metal atom, instead of two. He is also tinkering with the recognition sites on the edges of the molecule — the role fulfilled by rhodium in this case. "We have a whole series of systems in the works," he says. 

  • References

    1. Yoon, H. J. & Mirkin, C. A. J. Am. Chem. Soc. doi: 10.1021/ja804076q (2008).
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