Hydrophilic crosslinked polymer
The present invention relates to a hydrophilic crosslinked polymer, preferably in the form of porous particles, and to the preparation and use thereof. The polymer according to the invention is produced by polymerisation from chain-forming hydrophilic vinyl ethers and crosslinking, preferably heterocyclic divinyl ethers.
1. A polymer based on a copolymer at least comprising
a) at least one hydrophilically substituted alkyl vinyl ether of formula I
where
R1, R2, R3, independently of one another, is H or C1 to C6 alkyl, and
R4 is a radical which carries at least one hydroxyl group,
and
b) at least one crosslinking agent of formula II and/or III and/or IV
where
X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH,
where
Y1 and Y2 in formula III and IV
are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or
C6 to C18 aryl, where one or more H atoms in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and
A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl groups, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH,
which polymer
has been derivatised by separation effectors, or
has been derivatised by structures which have been attached to the polymer by graft polymerisation, or
has been derivatised by structures which have been attached to the polymer by graft polymerisation with cerium(IV) catalysis.
2. A polymer according to claim 1 , wherein R4 in formula I is
a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or a
cycloaliphatic radical, , in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or a
C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or a
C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent.
3. A polymer according to claim 1 , wherein the hydrophilically substituted alkyl vinyl ether is a compound of formula I in which R4 is a radical which carries a hydroxyl group.
4. A polymer according to claim 1 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether.
5. A polymer according to claim 1 , wherein the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
6. A polymer according to claim 1 , which is porous having pore sizes between 2 and 200 nm.
7. A polymer according to claim 1 , which is in the form of particles having a diameter between 3 and 300 μm.
8. A polymer according to claim 1 , which has been derivatised by separation effectors.
9. A polymer according to claim 1 , which has been derivatised by structures which have been attached to the polymer by graft polymerisation.
10. A polymer according to claim 1 , which has been derivatised by structures which have been attached to the polymer by graft polymerisation with cerium(IV) catalysis.
11. A polymer according to claim 9 , wherein the structures are copolymers which have been produced from two or more different monomers.
12. A process for preparing a polymer, comprising copolymerizing, with addition of one or more porogens, at least one hydrophilically substituted alkyl vinyl ether of the formula I and at least one crosslinking agent of formula II and/or III and/or IV
where
R1, R2, R3, independently of one another, are H or C1 to C6 alkyl, and
R4 is a radical which carries at least one hydroxyl group,
and
where
X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH,
where
Y1 and Y2 in formula III and IV
are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or
C6 to C18 aryl, where one or more H in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and
A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH.
13. A process according to claim 12 , wherein in the compound of formula I, R4 is
a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or
a cycloaliphatic radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or a
C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or a
C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent.
14. A process according to claim 12 , wherein a free-radical suspension polymerisation is carried out.
15. A process according to claim 12 , wherein a free-radical suspension polymerisation is carried out in water as suspension medium in the presence of at least one suspension stabiliser and one or more optional further additives, inorganic salts or interface-active compounds.
16. A process according to claim 12 , wherein the temperature during the polymerisation is between 40 and 100° C.
17. A process according to claim 12 , wherein hydrophilically substituted alkyl vinyl ethers and crosslinking agents are in a weight ratio between 10:90 and 80:20.
18. A chromatography column, capillary or cartridge containing, as sorbent or support material, a polymer based on a copolymer at least comprising
a) at least one hydrophilically substituted alkyl vinyl ether of formula I
where
R1, R2, R3, independently of one another, is H or C1 to C6 alkyl, and
R4 is a radical which carries at least one hydroxyl group,
and
b) at least one crosslinking agent of formula II and/or III and/or IV
where
X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH,
where
Y1 and Y2 in formula III and IV
are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or
C6 to C18 aryl, where one or more H atoms in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and
A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced b O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl groups, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH.
19. A method of providing a sorbent in chromatography, support material for the immobilisation of biologically or catalytically active substances or support material for a solid-phase synthesis, comprising providing as the sorbent or support material a polymer based on a copolymer at least comprising
a) at least one hydrophilically substituted alkyl vinyl ether of formula I
where
R1, R2, R3, independently of one another, is H or C1 to C6 alkyl, and
R4 is a radical which carries at least one hydroxyl group,
and
b) at least one crosslinking agent of formula II and/or III and/or IV
where
X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH,
where
Y1 and Y2 in formula III and IV
are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or
C6 to C18 aryl, where one or more H atoms in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and
A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl groups, C1-C6)alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH.
20. A chromatography column, capillary or cartridge according to claim 18 , wherein R4 in formula I is
a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or a
cycloaliphatic radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or a
C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or a
C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent.
21. A chromatography column, capillary or cartridge according to claim 18 , wherein the hydrophilically substituted alkyl vinyl ether is a compound of formula I in which R4 is a radical which carries a hydroxyl group.
22. A chromatography column, capillary or cartridge according to claim 18 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether.
23. A chromatography column, capillary or cartridge according to claim 18 , wherein the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
24. A chromatography column, capillary or cartridge according to claim 18 , wherein the polymer is porous having pore sizes between 2 and 200 nm.
25. A chromatography column, capillary or cartridge according to claim 18 , wherein the polymer is in the form of particles having a diameter between 3 and 300 μm.
26. A chromatography column, capillary or cartridge according to claim 18 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether, and the the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
27. A polymer according to claim 1 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether, and the the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
28. A chromatography column, capillary or cartridge containing, as sorbent or support material, a polymer according to claim 1 .
29. A method of providing a sorbent in chromatography, support material for the immobilisation of biologically or catalytically active substances or support material for a solid-phase synthesis, comprising providing as the sorbent or support material a polymer according to claim 1 .
30. A polymer according to claim 1 , wherein R4 in formula I is
a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or a
cycloaliphatic radical having 5 to 10 C atoms, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or a
C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or a
C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent.