The use of optical spectroscopy in combinatorial chemistry.

Infrared and Raman spectroscopy allow direct spectral analysis of the solid-phase, thus avoiding the tedious cleavage of compounds from the solid support. With diagnostic bands in starting materials or products, infrared and Raman spectroscopy are efficient in monitoring each reaction step directly on the solid phase. Consequently, infrared and Raman spectroscopy have evolved as the premier analytical methodology for direct analysis on the solid support. While infrared transmission spectroscopy is a general analytical method for resin samples, internal reflection spectroscopy is especially suited for solid polymer substrates known as "pins" or "crowns." Single bead analysis is done best by infrared microspectroscopy, whereas photoacoustic spectroscopy allows totally nondestructive analysis of resin samples. With an automated accessory, diffuse reflection spectroscopy provides a method for high throughput on-bead monitoring of solid-phase reactions. Providing identification based on molecular structure, HPLC-FTIR is, therefore, complementary to LC-MS. Additionally, Raman spectroscopy as a complement to infrared spectroscopy can be applied to resin samples and-using a Raman microscope-to single beads. Fluorometry as an extremely sensitive spectroscopic detection method allows rapid quantification of organic reactions directly on the resin.