Analytical chemistry

Reactions assayed by magnets

Does it float or sink? And to what extent? The answers to these questions can be used to follow the course of chemical reactions on solid supports, and are obtained simply by using two magnets, a salt solution and a ruler.

A generation of children is familiar with the concept of levitation from the adventures of Harry Potter, and could be forgiven for thinking it unremarkable. Scientists will know of real-world examples — reports of levitating water-droplets1, cells2 and even frogs3 — but most of them probably think of it as nothing more than a curiosity. It's unlikely that anyone imagined that levitation could be used as a routine analytical tool. But in the Journal of the American Chemical Society, Mirica et al.4 show that magnetic levitation is a simple, viable way to follow the course of chemical reactions that occur on solid, diamagnetic supports, such as those routinely used by chemists to prepare peptides, nucleic acids and other organic molecules. (Diamagnetic materials are those that create a weak magnetic field in opposition to an external magnetic field.)

The authors use their levitation procedure to analyse beads made from insoluble polymers known as Merrifield resins — named after their inventor Robert Merrifield, who won a Nobel prize in 1984 for his discovery5. These polymers were originally used as ion-exchange resins6 (which trap ions in analytical and purification procedures), but they were widely adopted by synthetic chemists as solid supports for reactions after Merrifield described their use for making peptides. Beads of Merrifield resins quickly became standard tools for preparing biologically important molecules; indeed, they enabled the biotechnology revolution. Nowadays, they are used in all manner of organic syntheses, not only as supports for reactions (for example, in combinatorial chemistry), but also as supports for reagents and catalysts7 (because such resin-bound compounds are easily removed by filtration from reaction mixtures in solution, greatly simplifying purification procedures).

Although polymer-supported reactions have been widely used for almost 50 years, the procedures available to monitor them are surprisingly limited8. Gel-phase nuclear magnetic resonance spectroscopy is the most useful technique, but this requires sophisticated instruments and is not always practical as a real-time assay. Colorimetric assays — which, as the name suggests, qualitatively monitor the amount of colour formed in a test reaction — can sometimes provide a rapid, qualitative assessment of the extent of a resin-bound reaction. But up to now, no analytical procedure could provide an almost instantaneous, qualitative and general assay of the progress of solid-supported reactions. Mirica and colleagues' technique4 promises to change that.

The authors' method requires only a test tube, a pair of commercially available magnets and an inexpensive solution of gadolinium chloride (GdCl3) in water (Fig. 1). When polymeric beads are suspended in the solution in a vertical magnetic field, the height at which they float depends on the balance between the gravitational and magnetic forces acting on them. This in turn depends on the density of the polymer, which changes when reactions occur on the beads. Mirica et al. thus monitored changes in the 'floating height' of beads to follow the progress of chemical reactions on the beads.

Figure 1: Sink or levitate.
figure1

a, Many synthetic reactions are performed using polymeric beads. Each bead is typically 75–150 micrometres in diameter, so many hundreds of beads are used in each reaction. (Beads are not shown to scale). b, When added to a solution of gadolinium chloride (GdCl3) in a magnetic field, such beads levitate. The height at which they levitate depends on their density, which varies during the course of a reaction. c, Mirica et al.4 use this effect to follow the progress of solid-supported reactions. In their method, beads are removed at intervals from a reaction, and changes in the height at which they levitate are observed. When no further change in levitation height is observed for successive beads, the reaction is complete.

The authors' method for tracking the course of solid-supported reactions is considerably simpler than previously available methods, which require more-complex instruments and are more limited in scope. Furthermore, the levitation analysis is sensitive enough to detect even slight changes in density between beads. Mirica et al. thus showed that their method could be used not only to determine when a reaction is complete, but also to follow reaction kinetics. Differences in floating heights could also be used to separate mixtures of beads that have different densities9.

Although the levitation procedure described is clearly useful, its advantages and limitations still have to be defined. For example, the authors show that, at the mid-point of a reaction, a broader range of floating heights is obtained than at the beginning or end of the reaction. This could complicate some analyses. It also seems that, for the best results, the beads should all be the same size (which isn't always the case), and that traces of solvent adsorbed to the beads can affect the outcome of the assay. On the other hand, opportunities exist to optimize the technique, by designing synthetic processes or resins that maximize changes in density caused by reactions, or by devising an automated version of the method that uses optical sensors to monitor changes in the heights of floating beads — currently, the authors measure the heights by hand using a millimetre-scale ruler.

Chemistry evolves through the invention of new reactions or catalysts, and less commonly through the discovery of new ways of doing things. Mirica and colleagues' gravimetric levitation analysis falls into the second category. Scientists who have the seemingly simple — but practically difficult — problem of monitoring the course of reactions on solid supports now have a new, easy way to do it.

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Bergbreiter, D. Reactions assayed by magnets. Nature 457, 805 (2009). https://doi.org/10.1038/457805a

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