Molecularly imprinted beaded polymers and stabilized suspension polymerization of the same in perfluorocarbon liquids

• US 5,872,198 A
• Filed: 05/27/1997
• Issued: 02/16/1999
• Est. Priority Date: 05/26/1995
• Status: Expired due to Term

• Current Assignee: Andrew G. Mayes, Klaus Mosbach
• Original Assignee: Andrew G. Mayes, Klaus Mosbach
• Inventors: Mosbach, Klaus, Mayes, Andrew G.
• Primary Examiner(s): Schofer, Joseph L.
• Assistant Examiner(s): SAROFIM, NABIL F
• Application Number:
  US08/863,240
• Time in Patent Office: 630 Days
• Field of Search: 525/199, 525/200, 525/326.2, 525/326.3, 526/243, 526/215, 526/318.43, 526/201
• US Class Current: 526/201
• CPC Class Codes: B01D 15/3852 using imprinted phases or molecular recognition; using imprinted phases
• CPC Class Codes: B01J 20/26 Synthetic macromolecular compounds
• CPC Class Codes: B01J 20/268 Polymers created by use of a template, e.g. molecularly imprinted polymers
• CPC Class Codes: C07B 57/00 Separation of optically-active compounds
• CPC Class Codes: C08F 2/20 with the aid of macromolecular dispersing agents
• CPC Class Codes: C08F 2/44 Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
• CPC Class Codes: C08F 220/286 and containing polyethylene oxide in the alcohol moiety, e.g. methoxy polyethylene glycol (meth)acrylate
• CPC Class Codes: C08F 220/387 and containing nitrogen and oxygen
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template

Abstract

A suspension polymerization technique is provided for molecular imprinting based on the use of a perfluorocarbon liquid as the dispersing phase that does not interfere with the interactions between functional monomers and print molecules required for the recognition process during molecular imprinting, and provides controllable particle sizes within less than about 5 μm to about 100 μm.

Claims

1. A suspension polymerization process comprising,

a) forming a reaction mixture containing:

1) a mixture of distinct acrylic monomers;

2) at least one crosslinking agent;

3) at least one initiator;

4) at least one molecular imprint molecule; and

5) at least one porogenic solvent; and

,

b) polymerizing said reaction mixture in the presence of a stabilizer containing perfluorocarbon and polyoxyethylene ester groups to form molecularly imprinted polymer particles.

2. The process according to claim 1, wherein said stabilizer is chemically inert.

3. The process according to claim 1, wherein said acrylic monomers are methacrylic acid and ethylene glycol dimethacrylate.

4. The process according to claim 1, wherein said stabilizer is a polymer defined by the formula ##STR5## wherein, X is C_n F_2n+1 SO₂ N(C₂ H₅)C₂ H₄ O--, C_n F_2n+1 O-- or C_n F_2n+1 SO₂ N(C₂ H₅)C₂ H₂ --O--;

Y is (Z)_t CH₃ O(CH₂ CH₂ O)_m C₂ H₄ --O or (Z)_t CH₃ O(CH₂ CH₂ O)_m -- and Z is a print molecule;

n is between 1 and 20;

m can be zero to about 500;

p is at least 1;

q can be zero or any positive number;

r is 1-20, preferably 1 or 2;

s is zero or 1; and

t is zero or 1.

5. The process according to claim 1, wherein said stabilizer is a polymer defined by the formula ##STR6## wherein, X is C_n F_2n+1 SO₂ N(C₂ H₅)C₂ H₄ --O;

Y is CH₃ O(CH₂ CH₂ O)_m C₂ H₄ --O;

n is between 1 and 20;

m is zero to about 500;

p is at least 1; and

q is zero or any positive number.

6. A process according to claim 1, wherein prior to polymerization an emulsion is formed from components 1-5 and said stabilizers.

7. A process according to claim 6, wherein the reaction mixture is mixed for approximately 5 minutes at about 2000 rpms to form said emulsion.

8. A process according to claim 6, wherein the polymerization is conducted at temperatures between less than about 20°

C. and about 30°

C.

9. A process according to claim 1, wherein said polymerization is initiated by ultraviolet radiation.

10. A process according to claims 1, 4 or 5, wherein said polymer particles are beads.

11. A process according to claim 2, wherein said polymer particles provide a uniform surface for reproducible surface presentation.

12. A process according to claim 7, wherein said beads are spherical in shape.

13. A process according to claim 10, wherein said beads have a diameter of from about 2 to 100 microns.

14. A process according to claim 10, wherein said beads have a diameter of between 2 and 50 microns.

15. A process according to claim 10, wherein said beads have a diameter of between about 5 and 25 microns.

16. A process according to claim 1, wherein said porogenic solvent is selected from the group consisting of acetone, chloroform and toluene.

17. A process according to claim 1, wherein said molecular imprint molecule is capable of separating or resolving amino-acids, amino-acid derivatives, pharmaceutical compounds and polysaccharides.

18. A process according to claim 1, wherein said molecular imprint molecule is selected from D- and L-Boc amino acids and their derivatives.

19. A process according to claims 4 or 5, where s is zero.

20. A process according to claim 4, wherein s is 1.

21. A process according to claim 4, where t is 1.

22. A process according to claim 4, wherein said print molecule is selected from D- and L-Boc tryptophans, D- and L-Boc phenylanalines, D- and L-phenylanalines, D- and L-Boc-proline-N-hydroxsuccinimide esters, D- and L-Cbz tryptophans, D- and L-Cbz-aspartic acids, D- and L-Cbz-glutamic acids, D- and L-Cbz-tryptophan methyl esters, nitrophenyl α

and β

, D-, L-galactosides, (S)-(-) timolol, D-fructose, D-galactose, phenyl α

-D-mannopyranoside, acryl α and

β

glucosides, (R)-phenylsuccinic acid, Ac-L-Trp-OEz, L-Pheβ

NA, L-LeuAn, L-PheAn, L-PheGlyAn, L-MenPheAn, L-PyMePheAn, L-PLPheAn, N-Ac-L-Phe-L-Trp-OMe, diazepham, propranolol and ephidrine.

24. A process according to claim 5 wherein said molecular imprint molecule is capable of separating or resolving amino-acids, amino-acid derivatives, pharmaceutical compounds and polysaccharides.

25. A process according to claim 4 wherein said molecular imprint molecule is selected from D- and L-Boc amino acids and their deriavatives.

26. A process according to claim 5 wherein said molecular imprint molecule is selected from D- and L-Boc amino acids and their derivatives.

23. A process according to claim wherein 4 said molecular imprint molecule is capable of separating or resolving amino-acids, amino-acid deriavatives, pharmaceutical compunds and polysaccharides.