Combination of Single Bead FTIR and Chemometrics in Combinatorial Chemistry: Application of the Multivariate Calibration Method in Monitoring Solid-Phase Organic Synthesis.

The single bead FTIR method has been used in quantitative analyses of solid-phase organic synthesis (SPOS) such as the determination of reaction kinetics and conversion yield. These studies rely on data analysis methods to extract quantitative information from IR spectra. However, the IR spectrum of a solid-phase sample contains vibrational bands from the starting material, product, and the polymer support itself. The coexistence of multiple chemical components causes severe spectral overlaps and sometimes makes quantitative analysis extremely difficult. In some cases, it is impossible to extract qualitative and quantitative information from overlapped IR spectra. In this paper, we use partial least squares (PLS), a chemometrics method, to achieve qualitative and quantitative analysis of samples that generate severely overlapped IR spectra. The primary loading factor obtained from a PLS calculation only displays those spectral features that have undergone changes during a SPOS reaction. Disappearing and emerging organic functional groups generate negative and positive signals, respectively, in the primary loading factor, thus allowing qualitative analysis of the reaction with improved precision. The scores of the primary loading factors of spectra taken at various times during a reaction provide quantitative information allowing the study of the reaction kinetics directly on solid support. On the basis of the analysis of three diverse SPOS reactions, the PLS method has demonstrated the unique capability of extracting quantitative and qualitative information from the overlapped IR spectra. It is a powerful data analysis tool for the monitoring of SPOS reactions in combinatorial chemistry.