Modified siliceous chromatographic supports

• US 4,724,207 A
• Filed: 08/22/1984
• Issued: 02/09/1988
• Est. Priority Date: 02/02/1984
• Status: Expired due to Term

• Current Assignee: Specialty Minerals Incorporated (Minerals Technologies Incorporated)
• Original Assignee: Cuno Incorporated (3M Company)
• Inventors: Liao, Tung-Ping D., Hou, Kenneth C.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/643,613
• Time in Patent Office: 1,266 Days
• Field of Search: 435/177, 435/180, 435/181, 524/451, 525/342, 525/320 R, 525/326.7, 525/327.3, 424/85, 424/88, 210/656, 210/660, 210/692
• US Class Current: 435/180
• CPC Class Codes: B01D 15/361 Ion-exchange
• CPC Class Codes: B01D 15/362 Cation-exchange
• CPC Class Codes: B01D 15/363 Anion-exchange
• CPC Class Codes: B01D 15/3804 Affinity chromatography
• CPC Class Codes: B01J 20/103 comprising silica
• CPC Class Codes: B01J 20/14 Diatomaceous earth
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/264 derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
• CPC Class Codes: B01J 20/265 modified or post-treated polymers polymer carriers or substrates subjected to further impregnating or coating B01J20/3208
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/28016 Particle form
• CPC Class Codes: B01J 20/28033 Membrane, sheet, cloth, pad, lamellar or mat
• CPC Class Codes: B01J 20/28038 Membranes or mats made from fibers or filaments
• CPC Class Codes: B01J 20/28057 Surface area, e.g. B.E.T specific surface area
• CPC Class Codes: B01J 20/28078 Pore diameter
• CPC Class Codes: B01J 20/286 Phases chemically bonded to a substrate, e.g. to silica or to polymers
• CPC Class Codes: B01J 20/287 Non-polar phases; Reversed phases
• CPC Class Codes: B01J 20/3092 Packing of a container, e.g. packing a cartridge or column of chromatography columns B01D15/206
• CPC Class Codes: B01J 20/3204 Inorganic carriers, supports or substrates
• CPC Class Codes: B01J 20/3217 Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
• CPC Class Codes: B01J 20/327 : Polymers obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3276 : Copolymers
• CPC Class Codes: B01J 20/3278 : Polymers being grafted on the carrier
• CPC Class Codes: B01J 20/328 : Polymers on the carrier being further modified
• CPC Class Codes: B01J 20/3282 : Crosslinked polymers
• CPC Class Codes: B01J 20/3293 : Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers
• CPC Class Codes: B01J 2220/54 : Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/58 : Use in a single column
• CPC Class Codes: B01J 39/17 : containing also inorganic materials, e.g. inert material coated with an ion-exchange resin
• CPC Class Codes: B01J 39/26 : Cation exchangers for chromatographic processes

Abstract

A modified silica material which comprises silica covalently bonded to a synthetic polymer, the synthetic polymer being made from (a) a polymerizable compound capable of being covalently coupled directly to said silica, and (b) one or more polymerizable compounds containing (i) an ionizable chemical group, (ii) a chemical group capable of transformation to an ionizable chemical group, (iii) a chemical group capable of causing the covalent coupling of the compound (b) to an affinity ligand or a biologically active molecule or (iv) a hydrophobic compound.

Claims

1. A modified silica material which comprises:

(1) silica covalently bonded to a synthetic polymer;

(2) said synthetic polymer comprising a copolymer made from a free-radical polymerization of

(a) a polymerizable compound containing an epoxy group capable of direct covalent coupling to a hydroxy group of said silica and a vinyl group, capable of free-radical polymerization; and

(b) a polymerizable compound having the formula ##STR10## wherein R is an alpha, beta-ethylenically unsaturated polymerizable radical, R'"'"' and R" are the same or different C₁ -C₆ alkyl or alkanoyl groups, and R'"'"'" is a direct bond or a C₂ -C₃ alkyl group, wherein R'"'"' and R", taken together with the N atom may form a heterocyclic ring.

2. The material of claim 1 wherein said synthetic polymer also contains up 20% by weight of a neutral radical polymerizable compound, different than those represented by said polymerizable compound (b).

3. The material of claim 1 wherein said polymerizable compound (b) has been reacted with an affinity ligand.

4. The material of claim 1 wherein said polymerizable compound (b) has been reacted with a biologically active molecule.

5. The material of claim 1 wherein said silica is selected from talc, kaolinite, pyrophyllite, serpentine, smectite, montmorillonite, mica, vermiculite, silica gel, silica powder, porous glass, kieselguhr or diatomaceous earth.

6. The material of claim 1 wherein said compound (b) is a mixture of two or more compounds carrying different ionizable chemical groups.

7. The material of claim 1 wherein the amount of said compound (a) in said synthetic polymer is sufficient to cause substantial covalent coupling of the polymer to said silica, yet insufficient to cause substantial loss of porosity of the modified silica.

8. The material of claim 2 wherein said polymer has 1 to 500 units.

9. The material of claim 8 wherein said polymer has 20 to 100 units.

10. The material of claim 1 wherein said synthetic polymer is crosslinked.

11. The material of claim 10 wherein said crosslinking is provided by making said synthetic polymer in the presence of a compound having at least two radical polymerizable bonds.

12. The material of claim 10 wherein said synthetic polymer carries nitrogen atom-containing groups and said crosslinking is provided by means of bifunctional reagents capable of reacting with at least two of said nitrogen atoms per reagent.

13. The material of claim 12 wherein said reagent is ##STR11## Hal--CH₂ --phenyl--CH₂ --Hal, Hal--(CH₂)--_n Hal, or ##STR12## where Hal is a halogen atom, or ##STR13## and n is 2 to 12.

14. The material of claim 3 wherein said affinity ligand is an enzyme, a nucleic acid, an antigen, an antibody, a saccharide, a lectin, an enzyme cofactor, an enzyme inhibitor or a binding protein.

15. The material of claim 4 wherein said biologically active molecule is an enzyme.

16. A self-supporting silica matrix which comprises the material of any of claims 1, 3 or 4.

17. The matrix of claim 16 which also comprises highly refined cellulose pulp with a Canadian Standard Freeness of between +100 to -600 ml.

18. The matrix of claim 16 which also comprises a particulate different from the modified silica.

19. The matrix of claim 18 wherein said particulate is siliceous.

20. The matrix of claim 8 wherein said particulate has been chemically modified to carry ionizable chemical groups.

21. The matrix of claim 19 wherein said siliceous particulate has been modified with silane groups.

22. The matrix of claim 18 wherein said particulate has an average particle diameter between 1 millimicron and 100 microns.

23. The matrix of claim 16 which is in the form of a sheet.

24. In a method of ion exchange chromatography, the improvement comprising utilizing as the ion exchanger the material of claim 5.

25. In a method of affinity chromatography, the improvement comprising utilizing as the insoluble ligand support the material of claim 3.

26. In a method of carrying out chemical reactions using an insolubilized biologically active molecule, the improvement comprising wherein the insoluble support for said molecule is the material of claim 4.

27. The methods of any of claims 24, 25 or 26 wherein said material is in the form of a self-supporting silica matrix.

28. The method of claim 27 wherein said matrix also comprises a particulate different from the modified silica.

29. The method of claim 28 wherein said particulate different from silica carries ionizable chemical groups.

30. The method of claim 27, wherein said sheet is in the form of a sheet.

31. The method of claim 30, wherein said sheet is in the form of a disc.

32. A process for preparing the modified silica material of claim 1 which comprises:

(1) polymerizing said compound (a) which has a group capable of reacting with the hydroxy group of said silica, with said compound (b) in the presence of said silica, under temperature and pH conditions insufficient to cause the covalent binding of said compound (a) to said silica thereby to form a synthetic polymer of (a) and (b);

(2) reacting said silica with the chemical group of compound (a) in said synthetic polymer under temperature and pH conditions sufficient to cause covalent bonding of said polymer to said silica.

33. The process of claim 32 wherein said step (2) is carried out at a temperature which is higher than that used for step (1).

34. The process of claim 32 wherein said step (1) polymerization is initiated by redox initiation or photochemical initiation.

35. The process of claim 32, wherein said compound (a) carries nitrogen atom-containing groups and which further comprises the step of

(3) crosslinking said synthetic polymer which modifies said silica with a bifunctional crosslinking agent capable of reacting with at least two of said nitrogen atoms per reagent.

36. A chromatography column for effecting chromatographic separation of at least two components of a sample flowing therethrough comprising:

at least one solid stationary phase having a longitudinal axis, said phase having chromatographic functionality and being effective for chromatographic separation;

a means for radially distributing the sample through the stationary phase;

wherein the stationary phase comprises;

(a) a swellable fibrous matrix in sheet form having chromatographic functionality and being effective for chromatographic separation, spirally wound around the longitudinal axis of the solid phase to form a plurality of layers around the axis;

(b) a spacer means between each layer for permitting controlled swelling thereof and enhancing the distribution of sample flowing radially through the stationary phase,

and further wherein the swellable fibrous matrix in sheet form comprises a modified silica material, said modified silica material comprising the material of claim 1.