Radiation grafted surfaces for solid phase synthesis 'effect of grafting depth on solid support performance'

Solid phase synthesis (SPS) has developed rapidly throughout the last decade. Pharmaceutical companies have committed significant resources to the development of high throughput solid phase synthesis and combinatorial chemistry handling capabilities, which resulted in increased synthesis throughput for drug discovery research. The most widely used solid supports for SPS are based on cross-linked styrene-divinylbenzene resin (Merrifield resins) and their derivatives. However, with the increasing demand for reaction reproducibility, consistency of reaction kinetics and efficiency, as well as ease in parallel handling, the 'pellicular' type support is more attractive than traditional polystyrene resin for SPS. A pellicular solid support consists of a polymer, such as polystyrene, grafted to a rigid plastic such as a polyolefin or fluorinated polymer. A series of 'pellicular' type supports were fabricated by direct gamma radiation mediated graft polymerisation of styrene onto polypropylene, followed by functionalization (aminomethylation). In this study, we report the effect of grafting conditions, which include polymer type, radiation dose rate and total dose, concentration of monomer and solvents on the grafting depth profile and coupling reaction rates of functionalisation polystyrene grafted polypropylene surfaces. Confocal Raman spectroscopy was used for measuring the level of penetration of polystyrene graft into polypropylene and other structural features such as density of graft and depth of functionalization. Raman spectroscopy results showed that the calculated rate coefficient for coupling of Fmoc-labelled amino acids was primarily dependent on graft thickness, but was also influenced by the proportion of polystyrene graft to polypropylene. In general, it was also shown that with increasing loading capacity of the support the calculated rate coefficient for amino acid coupling decreased correspondingly. In addition, a new approach was used to prepare a high surface area support that had both a high rate coefficient and a high loading capacity