Synthesis of biocompatible polymers. 1. Homopolymerization of 2-methacryloyloxyethyl phosphorylcholine via ATRP in protic solvents: An optimization study

Biocompatible polymers based on 2-methacryloyloxyethyl phosphorylcholine (MPC) have delivered clinically proven benefits in various biomedical applications. In a recent communication [Lobb, E. J.; et al. J. Am. Chem. Soc. 2001, 123, 7913-7914], we reported that MPC can be polymerized to high conversions in both water and methanol at ambient temperature via atom transfer radical polymerization (ATRP). Low polydispersities were obtained, but the living character of this polymerization was not thoroughly explored. In the present paper we report a more detailed optimization study of the ATRP of MPC. Excellent yields, first-order monomer kinetics, linear M-n vs conversion plots, and relatively narrow polydispersities (M-w/M-n = 1.15-1.35) were obtained in both aqueous and alcoholic media at 20 degreesC. However, slower polymerizations and narrower polydispersities were always obtained in alcoholic solution, and chain extension experiments indicated significantly greater living character (i.e., greater self-blocking efficiency) under these conditions. The rate of ATRP was significantly slower in 2-propanol (IPA) than methanol due to the reduced polarity of the former solvent. However, acceptable rates of polymerization and reasonable control were obtained at elevated temperature in IPA. Alternatively, the addition of a relatively small amount of water to the IPA led to a significantly faster polymerization at ambient temperature. The effect of varying,the ligand type and target DPn was also investigated. The best results were obtained using 2,2'-bipyridine for target DPn's of 20-200, with two alternative ligands giving either inferior control or slower rates of polymerization. Higher target DPn's resulted in significantly higher polydispersities even when using the 2,2'-bipyridine ligand. The spent ATRP catalyst was conveniently removed by treating aqueous solutions of MPC homopolymer with silica. This produced residual catalyst levels of less than 2 ppm, as measured by inductively coupled plasma atomic emission spectrometry, which may be sufficiently low for some biomedical applications. This synthetic advance is expected to allow the preparation of a wide range of novel biocompatible diblock and triblock copolymers for various biomedical applications.