Many methods for preparing porous polymeric supports useful in various separation applications are known today, such as suspension polymerisation of synthetic or native monomers. In order to improve the properties of so prepared supports, various strategies have also been suggested for modification of their surfaces. Such surface-modifications may for example be performed in order to enhance the available surface area of a support, to facilitate subsequent derivatisation with ligands for chromatography, to modify the hydrophobic/hydrophilic surface thereof etc.
One such surface modification is suggested in WO 95/13861 (Ericsson et al), wherein hydrophilic poly(vinyl ethers) are polymerised by cationic polymerisation to subsequently be coupled to the surface of a porous polymeric support, such as agarose. The method disclosed necessarily involves a step of protecting the hydroxyl group of the vinyl ether monomer before the polymerisation and a corresponding step for deprotection thereof in the polymer obtained. Thus, a drawback of the method described is the number of process steps required to obtain a surface-modified product.
It is known from EP 0 337 144 (Merck Patent Gesellschaft mit beschränkter Haftung) to graft chromatographic supports in order to develop separation materials, which are universally employable in chromatography. The grafting is effected in the course of customary redox polymerisation. Cerium(IV) ions are employed as polymerisation catalyst in order to form radical sites on the pore surfaces of support particles. Thus, one object of EP 0 337 144 is to improve the dissolving ability as compared to the known materials, which is provided by use of hydrophilic separation based on supports containing hydroxyl groups, the supports of which are coated with covalently bonded polymers. More specifically, the polymers are bonded to the support via radicals generated at the α-C atoms of the hydroxyl groups, and this kind of grafting therefore represent the principle “grafting from”, see e.g. P F Rempp, P J Lutz: Comprehensive Polymer Science vol. 6, pp 403–421, Eds. G Allen et al, Oxford 1989. This technique is based on the initiation of polymerisation by a limited number of radicals on the support surfaces and is accordingly sensitive to termination by eg oxygen. The preferred monomers are monomers with a high rate of propagation, which typically means acrylamide, acrylate or methacrylate monomers, which also are those mentioned in the application.
U.S. Pat. No. 5,929,214 (Peters et al) discloses porous synthetic polymer monoliths wherein the pores contain grafted temperature-responsive polymers and copolymers. These monoliths are especially suitable for use as thermal gates or thermal valves. The pores in such monoliths are greater than about 600 nm in diameter, and therefore the polymers need to be of a sufficient size to occlude such macropores. Suitable monomers to form the thermally responsive polymers grafted onto the support of the pores are known and include acrylamides and methacrylamides substituted on the nitrogen atom with slightly hydrophobic groups, vinylcaprolactam, methyl vinyl ether, 3-hydroxypropylacrylate, vinyl acetate, 2-(C.sub.2–C.sub.6)-alkyl-1-vinyloxazolines, ethylene oxide, propylene oxide, as well as copolymers thereof with copolymerisable comonomers which do not preclude thermal responsiveness of the resulting polymer. Suitable comonomers, e.g. methylenebisacrylamide with N-alkylacrylamide, may be used to provide cross-linking and controllable swelling or other desirable properties. The polymers produced according to U.S. Pat. No. 5,929,214 undergo a rapid and reversible phase transition from a first structure, below their lower critical solution temperature (LCST), to a second structure, above their LCST, and are therefore referred to as “thermo-shrinking” polymers.
Dhal et al (Dhal, Pradeep K.; Vidyasankar, S.; Arnold, Frances H. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, Calif., USA. Chem. Mater. (1995), 7(1), 154–62) have disclosed surface grafting of functional polymers to macroporous poly(trimethylolpropane trimethacrylate). The type of functional monomer is selected in order to retain the physical properties of the original matrix.
U.S. Pat. No. 5,865,994 (Dionex Corporation) discloses a bifunctional cation-exchange composition comprised of crown ether functional groups, which allow formation of a complex with a cation, and non-crown ether cation-exchange functional groups, which are capable of charge-interaction with cations. Preferred non-crown ether functional groups are sulphonate, carboxylate and phosphonate groups. In U.S. Pat. No. 5,865,994, a comparative example of a standard cation-exchange resin is provided, wherein maleic anhydride and ethyl vinyl ether are grafted onto a macroporous polymeric resin. In the field of chromatography, the term “macroporous” is used for particles that are porous both in a dry or wet state, as compared to gelporous particles that are porous only in the wet state. Examples of the first group are e.g. the synthetic polymers, such as divinylbenzene and styrene, while the latter can be exemplified by various polysaccharides, such as agarose. In this context, it is well known that vinyl ethers in general are very difficult to polymerise as the sole monomer. See e.g. “Principles of Polymerization”, Third Edition, page 200, Author: George Odian, and publisher: John Wiley & Sons, Inc., wherein in Table 3-1, the family of vinyl ethers are rated as a − (minus) for radical polymerisation. However, in the comparative example discussed above and presented in U.S. Pat. No. 5,865,994, the polymerisation is possible since the maleic acid anhydride will act as an electron acceptor while the ethyl vinyl ether will act as the electron donor.
Finally, it is known from U.S. Pat. No. 5,503,933 to form a hydrophilic-coated support, which comprises a hydrophobic domain including an unsaturated group and a hydrophilic domain. Hydrophilic coatings can e.g. be covalently attached to hydrophobic polymers, such as divinylbenzene cross-linked polystyrene. The purpose of the coatings described is to mask the hydrophobic supports and to provide a polymer, which is chemically stable at high and low extremes in pH.