Credit: © 2008 ACS

Solid-supported synthesis is the method of choice when preparing peptides, nucleic acids and libraries of closely related molecules. However, when attempting to transfer new chemistry to the solid phase, the major problem is the lack of a simple analytical technique that would allow the progress of reactions to be followed in real time. When performing solution-phase chemistry, the standard is thin-layer chromatography (TLC), but no equivalent exists for solid-supported synthesis. The only answer is to sacrifice a small amount of the beads, cleave the products from the support and analyse by standard solution-phase methods such as proton NMR.

Now, George Whitesides and co-workers from Harvard University have found1 that magnetic levitation can be used to assess atomic-level changes in polymer composition — a method that could become the TLC of solid-supported synthesis. A polymer bead, to which the reacting molecule is bound, is suspended in an aqueous solution of gadolinium chloride. When placed between two magnets, the bead levitates at a height where the magnetic and gravitational forces are balanced. The method is sensitive enough to detect small changes in the structure of the attached molecules, and thus the levitation height of the bead can be used to follow the progress of a reaction.

Whitesides and co-workers even used the technique to determine the kinetics of a solid-supported reaction. The results agreed with those generated by the far more laborious method of cleaving the products and analysing the conversion by proton NMR.