Progression of Organic Reactions on Resin Supports Monitored by Single Bead FTIR Microspectroscopy.

We report the time courses of five solid-phase reactions obtained using single bead FTIR microspectroscopy. This time-resolved information aided in the determination of the required reaction time, the nature of the solid-phase reaction, and resin property, effectively assisting in the initial phase of our combinatorial chemistry efforts. Our results showed that solid-phase organic reactions proceed faster than generally speculated. In addition, we have shown that reactions on the surface and in the interior of the bead occur at the same rate for reactions studied. The reaction on the TentaGel resin was shown to be not faster than reactions on Wang resin, suggesting that the diffusion of the substrate into polystyrene bead copolymerized with 1% divinylbenzene is not rate-limiting. Finally, the capability of obtaining IR spectra from the partial surface of a single bead demonstrated the femtomolar detection limit of single bead FTIR microspectroscopy.