Method for Coating the Internal Surface of a Reaction Vessel

• US 20070244324A1
• Filed: 12/23/2004
• Published: 10/18/2007
• Est. Priority Date: 12/23/2003
• Status: Active Grant

• Current Assignee: Hammersmith Imanet Limited
• Original Assignee: Hammersmith Imanet Limited
• Inventors: Arstad, Erik, Brady, Frank, Luthra, Sajinder, Jefferey, Nicholas
• Granted Patent: US 8,124,050 B2
• Time in Patent Office: Days
• US Class Current: 544/301
• CPC Class Codes: B01D 15/325 Reversed phase
• CPC Class Codes: B01D 15/327 with hydrophobic interaction
• CPC Class Codes: B01D 15/363 Anion-exchange
• CPC Class Codes: B01J 20/28014 characterised by their form
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 20/287 Non-polar phases; Reversed phases
• CPC Class Codes: B01J 2220/84 Capillaries
• CPC Class Codes: B01J 41/04 Processes using organic exchangers
• CPC Class Codes: B01J 41/12 Macromolecular compounds
• CPC Class Codes: C08G 61/08 of carbocyclic compounds containing one or more carbon-to-carbon double bonds in the ring
• CPC Class Codes: C09D 165/00 Coating compositions based on macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain C09D107/00 - C09D157/00, C09D161/00 take precedence; Coating compositions based on derivatives of such polymers
• CPC Class Codes: G01N 2030/567 coating
• CPC Class Codes: G01N 2030/77 detecting radioactive properties
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize

Abstract

The present invention involves the application of ROMP polymers to the internal surfaces of a device for the purpose of carrying out a solid-phase radiochemical process within the device. An additional embodiment of the invention is an automated synthesis system comprising a number of devices of the invention in order that a series of processes can be carried out in direct sequence. In a preferred embodiment, the present invention is a microfabricated device.

Claims

1. A method of coating the internal surface of a device with a polymer, the process comprising the steps of:

(i) introducing into the device a solution of one or more monomers in a suitable solvent;

(ii) introducing a flow of an inert gas through the device; and

(iii) initiating polymerisation of the monomer solution.

2. A method as claimed in claim 1 wherein the device is a microfabricated device or a reaction vessel with an internal diameter of less than about 2 mm

3. A method as claimed in claim 1, wherein the inert gas is nitrogen or argon.

4. A method as claimed in claim 1, wherein the device is a microfabricated device or a loop from 1 to 100 cm in length.

5. A method as claimed in claim 1, wherein the device is adapted to carry out a solid-phase radiochemical process.

6. A method as claimed in claim 1, wherein the one or more monomers can be polymerised by ring opening metathesis polymerisation (ROMP) and the solution also includes a ruthenium carbene catalyst and a cross-linker.

7. A method as claimed in claim 1, wherein polymerisation of the one or more monomers leads to a ROMP polymer of Formula (I):

wherein;

X is either a C_4-6 cycloalkyl or C_4-6 heterocyclyl moiety;

L is a C₁ to C₂₀ linker group comprising one or more alkyl, alkenyl, alkynyl, C_4-10 cycloalkyl, C_4-10 heterocyclyl, C_4-10 aryl, C_4-10 heteroaryl, ether, PEG, sulphide, amide,sulphamide or a combination thereof;

any of which may be substituted with one or more groups R²

R¹ is hydrogen, C_1-20 alkyl, C_2-20 alkenyl, C_2-20 alkynyl, C_4-12 cycloalkyl, C_4-12 heterocyclyl, aryl, heteroaryl, C(O)R³, C_1-20 alkyl-C(O)R³, C_2-20 alkenyl-C(O)R³, C_2-20 alkynyl-C(O)R³, nitro, isocyanate, C_1-10 alkyl-C(O)—

C(R⁴)₂—

C(O)—

C_1-10 alkyl, aminooxy, nitrile, phosphorus chloride, succinimide, sulphonyl chloride, halogen, tosylate, mesylate, triflate, nonaflate, silane, OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, quaternary phosphorous, C_1-20 alkyl-R⁵, C_2-20 alkenyl-R⁵ or C_2-20 alkynyl-R⁵ or a group comprising an enzyme or a catalyst.

R is C(O)R³, C_1-20 alkyl-C(O)R³, C_2-20 alkenyl-C(O)R³, C_2-20 alkynyl-C(O)R³, nitro, isocyanate, C_1-10 alkyl-C(O)—

C(R⁴)₂—

C(O)—

C_1-10 alkyl, aminooxy, nitrile, phosphorus chloride, succinimide, sulphonyl chloride, halogen, tosylate, mesylate, triflate, nonaflate, silane, OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, quaternary phosphorous, C_1-20 alkyl-R⁵, C_2-20 alkenyl-R⁵ or C_2-20 alkynyl-R⁵.

R³ is H, OH, C_1-20 alkyl, OC_1-20 alkyl, N(R⁴)₂, N⁺(R⁴)₃;

each R⁴ is independently H or C_1-10 alkyl;

R⁵ is OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, C_4-10 cycloalkyl, C_4-10 heterocyclyl, aryl or heteroaryl.

8. A process as claimed in claim 7, wherein, in the ROMP polymer of Formula (I):

R¹ is halogen, OH, SH, C_1-20 alkyl, C_4-12 aryl, C_1-20 alkyl-R⁵, C_1-20 alkyl-C(O)R³, N(R⁴)₂, N⁺(R⁴)₃ or a group comprising an enzyme or a catalyst.

where R³ is OH, R⁴ is as defined for general formula (I) and R⁵ is N(R⁴)₂, N⁺(R⁴)₃, aryl or heteroaryl;

9. A process as claimed in claim 8, wherein, in the ROMP polymer of Formula (I) wherein R¹ is C_1-20 alkyl;

—

N═

C═

O, —

SH or N⁺(R⁴)₃, particularly with bound ¹⁸F-fluoride ion or comprises an enzyme or a catalyst; and

R⁴ is as defined in general formula (I).

10. A process as claimed in claim 7, wherein the polymer of Formula (I) contains more than one R¹ group.

11. A process as claimed in claim 1 wherein polymerisation of the one or more monomers leads to a ROMP polymer of Formula (II):

wherein;

-L-, R¹ and n are as defined above for Formula (I).

12. A process as claimed in claim 1 wherein polymerisation of the one or more monomers leads to a ROMP polymer of Formula (III):

wherein;

R¹ and n are as defined above for Formula (I);

R² is an optional group as defined above for -L- of Formula (I); and

, q=1-4.

13. A process as claimed in claim 12, wherein, in the ROMP polymer of Formula (III), R¹ is trialkylammonium, R² is absent, q=3 and n=number of polymer units.

14. A process as claimed in claim 1, wherein each monomer is present in the starting solution in a concentration of from about 0.1 to 5M.

15. A process as claimed in claim 1 wherein, in the monomer solution, the solvent is a polar aprotic solvent.

16. A process as claimed in claim 1 wherein polymerisation is initiated by heating.

17. A process as claimed in claim 1 wherein polymerisation occurs spontaneously.

18. A process as claimed in claim 1, wherein the device is a microfabricated device and, the process of the invention comprises the initial step of creating a defined network of channels within the device.

19. A device comprising a microfabricated device or a reaction vessel with an internal diameter of less than about 2mm, wherein the internal surface is coated with a polymer substrate for a solid phase physical or chemical process.

20. A device as claimed in claim 19 adapted for carrying out a solid phase radiochemical process.

21. A device as claimed in claim 19, wherein the internal surface is coated with a ROMP polymer.

22. A device as claimed in claim 19, wherein the internal surface is coated with a polymer of Formula (I):

wherein;

X is either a C_4-6 cycloalkyl or C_4-6 heterocyclyl moiety;

L is a C₁ to C₂₀ linker group comprising one or more alkyl, alkenyl, alkynyl, C_4-10 cycloalkyl, C_4-10 heterocyclyl, C_4-10 aryl, C_4-10 heteroaryl, ether, PEG, sulphide, amide,sulphamide or a combination thereof;

any of which may be substituted with one or more groups R²

R¹ is hydrogen, C_1-20 alkyl, C_2-20 alkenyl, C_2-20 alkynyl, C_4-12 cycloalkyl, C_4-12 heterocyclyl, aryl, heteroaryl, C(O)R³, C_1-20 alkyl-C(O)R³, C_2-20 alkenyl-C(O)R³, C_2-20 alkynyl-C(O)R³, nitro, isocyanate, C_1-10 alkyl-C(O)—

C(R⁴)₂—

C(O)—

C_1-10 alkyl, aminooxy, nitrile, phosphorus chloride, succinimide, sulphonyl chloride, halogen, tosylate, mesylate, triflate, nonaflate, silane, OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, quaternary phosphorous, C_1-20 alkyl-R⁵, C_2-20 alkenyl-R⁵ or C_2-20 alkynyl-R⁵ or a group comprising an enzyme or a catalyst.

R² is C(O)R³, C_1-20 alkyl-C(O)R³, C_2-20 alkenyl-C(O)R³, C_2-20 alkynyl-C(O)R³, nitro, isocyanate, C_1-10 alkyl-C(O)—

C(R⁴)₂—

C(O)—

C_1-10 alkyl, aminooxy, nitrile, phosphorus chloride, succinimide, sulphonyl chloride, halogen, tosylate, mesylate, triflate, nonaflate, silane, OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, quaternary phosphorous, C_1-20 alkyl-R⁵, C_2-20 alkenyl-R⁵ or C_2-20 alkynyl-R⁵.

R³ is H, OH, C_1-20 alkyl, OC_1-20 alkyl, N(R⁴)₂, N³⁰ (R⁴)₃;

each R⁴ is independently H or C_1-10 alkyl;

R⁵ is OR⁴, SR⁴, N(R⁴)₂, N⁺(R⁴)₃, C_4-10 cycloalkyl, C_4-10 heterocyclyl, aryl or heteroaryl.

23. An automated synthesis system comprising two or more devices as claimed in claim 19 which are fluidly interconnected

24. A method for recovering of ¹⁸F-fluoride ion from ¹⁸O-enriched water containing ¹⁸F-fluoride ion, the process comprising passing the ¹⁸O-enriched water containing ¹⁸F-fluoride ion through a device as claimed in claim 19 or a system comprising two or more devices as claimed in claim 19 which are fluidly interconnected, in which the polymer coating comprises a ROMP polymer of general formula (III) in which R¹ is tri(C₁-₆ alkyl)ammonium, with a non-nucleophilic counter-ion, R² is absent and q is 3.

25. A method as claimed in claim 24 which is a step in the synthesis of an ¹⁸F-labelled radiotracer.

26. A method for the synthesis of an ¹⁸F-labelled radiotracer, the method comprising:

(i) recovering of ¹⁸F-fluoride ion from ¹⁸O-enriched water containing ¹⁸F-fluoride ion passing the ¹⁸O-enriched water containing ¹⁸F-fluoride ion through a device as claimed in claim 19 or a device comprising two or more devices as claimed in claim 19 which are fluidly interconnected, in which the polymer coating comprises a ROMP polymer of general formula (III) in which R¹ is tri(C₁-₆ alkyl)ammonium, with a non-nucleophilic counter-ion, R² is absent and q is 3; and

(ii) introducing into the device an unlabelled precursor compound of the ¹⁸F-labelled radiotracer such that ¹⁸F becomes incorporated into the precursor compound via nucleophilic substitution to form the ¹⁸F-labelled radiotracer.

27. A method as claimed in claim 26, wherein the ¹⁸F-labelled radiotracer is:

2-[¹⁸F]fluorodeoxyglucose (2-[¹⁸F]-FDG);

L-6-[¹⁸F]fluoro-DOPA;

3′

-deoxy-3′

-fluorothymidine (FLT);

2-(1,1-dicyanopropen-2-yl)-6-(2-[¹⁸F]fluoroethyl)-methylamino)-naphthalene ([¹⁸F]FDDNP);

5[¹⁸F]fluorouracil;

5[¹⁸F]fluorocytosine;

or

[¹⁸F]-1-amino-3-fluorocyclobutane-1-carboxylic acid ([¹⁸F]-FACBC).