Analysis of single polymer beads for solid phase combinatorial synthesis: the determination of reactive thiol and within batch polydispersity of beadloadings

Polymer beads are the starting point of many synthetic protocols, and in a number of combinatorial syntheses such studies are based on single beads. I t has therefore become important that individual beads carry the same funct ional group activity and quality control of populations of beads requires a knowledge of the distribution of activity between the individual beads. A procedure was developed for the measurement of the thiol loading of single copolymer beads which is based on the bleaching of Michler's hydrol [4,4'-b is(dimethylamino)diphenylcarbinol (BDC-OH)]. Flow injection colorimetry per mits the small volumes of solution generated from single beads to be measur ed with rapid turnover and with a reproducibility of ca. 2%. The solution d etection limit of 0.17 mM corresponds to a bead thiol concentration of 0.33 mmol g(-1). The procedure and the variability of a bead population were de monstrated using modified styrene-divinylbenzene copolymer beads. The appar atus allowed fast, simple and accurate determinations to be carried out on the individual polymer beads. Within a single batch of thiol-modified styre ne-divinylbenzene beads thiol loadings ranged from < 0.35 to 2.07 mmol g(-1 ) or 0.12 to 1.3 <mu>mol per bead. Polydispersity may therefore significant ly influence screening decisions based on single bead syntheses.