Combinatorial synthesis and analysis of organometallic compounds and homogeneous catalysts

• US 6,248,540 B1
• Filed: 09/03/1999
• Issued: 06/19/2001
• Est. Priority Date: 07/23/1996
• Status: Expired due to Term

• Current Assignee: Intermolecular Incorporated
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Turner, Howard, Powers, Timothy, Murphy, Vince, Goldwasser, Isy, McFarland, Eric, Boussie, Thomas, Weinberg, W. Henry, Van Beek, Johannes A. M.
• Primary Examiner(s): CELSA, BENNETT M
• Application Number:
  US09/390,001
• Time in Patent Office: 655 Days
• Field of Search: 502/1, 502/2, 502/102-103, 502/150, 502/527.14, 502/527.16, 502/527.17, 502/527.24, 435/4, 435/7.1, 436/518, 554/1
• US Class Current: 506/27
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00443 Thin film deposition
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00515 in the shape of strings
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00583 Features relative to the processes being carried out
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 : the surface being inorganic
• CPC Class Codes: B01J 2219/00621 : by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00644 : the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 : In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00738 : Organic catalysts
• CPC Class Codes: B01J 2219/00745 : Inorganic compounds
• CPC Class Codes: B01J 2219/00747 : Catalysts
• CPC Class Codes: B01J 2219/0075 : Metal based compounds
• CPC Class Codes: B01J 2219/00754 : Metal oxides
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07F 15/0066 : without a metal-carbon linkage
• CPC Class Codes: C07F 15/045 : without a metal-carbon linkage
• CPC Class Codes: C08F 10/00 : Homopolymers and copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond
• CPC Class Codes: C08F 4/7006 : NN
• CPC Class Codes: C08F 4/7081 : Neutral ligand
• CPC Class Codes: C40B 30/08 : by measuring catalytic activity
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01J 4/00 : Measuring polarisation of light
• CPC Class Codes: G01N 21/6402 : Atomic fluorescence; Laser induced fluorescence
• CPC Class Codes: G01N 2291/02818 : Density, viscosity
• CPC Class Codes: G01N 2291/0423 : Surface waves, e.g. Rayleigh waves, Love waves
• CPC Class Codes: G01N 2291/106 : one or more transducer arrays
• CPC Class Codes: G01N 29/036 : by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/2425 : optoacoustic fluid cells therefor
• CPC Class Codes: G01N 29/348 : with frequency characteristics, e.g. single frequency signals, chirp signals measuring frequency of mechanical vibrations or acoustic waves in general G01H1/06, G01H3/04; measuring frequency or analysing frequency spectra G01R23/00
• CPC Class Codes: G01N 29/4427 : with stored values, e.g. threshold values

Abstract

The present invention relates, inter alia, to methodologies for the synthesis, screening and characterization of organometailic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention provide for the combinatorial synthesis, screening and characterization of libraries of supported and unsupported organometallic compounds and catalysts (e.g., homogeneous catalysts). The methods of the present invention can be applied to the preparation and screening of large niumbers of organometallic compounds which can be used not only as catalysts (e.g., homogeneous catalysts), but also as additives and therapeutic agents.

Claims

1. A method for preparing an array of activated metal-ligand compounds, comprising:

(a) providing a first metal-binding ligand and a second metal-binding ligand to first and second regions on a substrate, wherein said first and second metal-binding ligands are different;

(b) providing a first metal ion to said first region and a second metal ion to said second region, wherein said first metal ion and said second metal ion are the same or different; and

(c) providing one or more activators to said first and second regions, wherein said activators are suitable co-catalysts for polymerization, thereby forming said array.

3. A method according to claims 1 or 2, wherein said providing step for said metal-binding ligands comprises delivering said ligand to said respective region.

4. A method according to claims 1 or 2, wherein said providing step for said metal-binding ligands comprises synthesizing said ligand in said respective region.

5. A method according to claims 1 or 2, wherein said providing step for said metal ions comprises delivering said metal ions to said respective region.

6. A method according to claims 1 or 2, further comprising deprotonating each of said first and second metal-binding ligands prior to providing said metal ions.

7. A method according to claims 1 or 2, wherein there are more than 3 activated metal-ligand compounds in said array as a result of following steps (a), (b) and (c) for each of said activated metal-ligand compounds.

8. A method according to claims 1 or 2, wherein there are at least 10 different activated metal-ligand compounds in said array as a result of following steps (a), (b) and (c) for each of said activated metal-ligand compounds.

9. A method according to claims 1 or 2, wherein there are at least 20 different activated metal-ligand compounds in said array as a result of following steps (a), (b) and (c) for each of said activated metal-ligand compounds.

10. A method according to claims 1 or 2, wherein there are more than 3 regions on said substrate and each region contains a metal-ligand compound after steps (a) and (b), which is activated in step (c).

11. A method according to claims 1 or 2, wherein there are at least 10 regions on said substrate and each region contains a metal-ligand compound after steps (a d (b), which is activated in step (c).

12. A method according to claims 1 or 2, wherein there are at least 20 regions on said substrate and each region contains a metal-ligand compound after steps (a) and (b), which is activated in step (c).

13. A method according to claims 1 or 2, wherein said first and second activator are independently selected from the group consisting of alumoxanes and (Q)⁺(NCA)⁻

, where Q is a reactive cation, NCA is a coordinating anion.

14. A method according to claims 1 or 2, wherein said first and second activator are independently selected from the group consisting of Lewis acids and ion-exchange activators.

15. A method according to claim 14, wherein said first and second activator are independently selected from the group consisting of methylalumoxane and B(C₆F₅)₃.

16. A method according to claims 1 or 2, wherein said first and second metal ions are independently selected from the group consisting of main group metal ions and transition metal ions.

17. A method according to claim 16, wherein said first and second metal ions are independently selected from the group consisting of transition metal ions.

18. A method according to claim 16, wherein said first and second metal ions are independently selected from the group consisting of Pd, Ni, Pt, Ir, Rh, Cr, Mo, W and Co.

19. A method according to claims 1 or 2, wherein said first and second metal-binding ligands have a coordination number (CN) independently selected from the group consisting of 1, 2 and 3.

20. A method according to claims 1 or 2, wherein said first and second metal-binding ligands have a charge independently selected from the group consisting of 0, −

1, −

2, −

3 and −

4.

21. A method according to claims 1 or 2, wherein said first and second metal-binding ligands have a coordination number (CN) and charge independently selected from the group consisting of (i) CN=2, charge=−

2;

(ii) CN=2, charge=−

1;

(iii) CN=1, charge=−

1;

(iv) CN=2, charge=neutral;

(v) CN=3, charge=−

1;

(vi) CN=1, charge=−

2;

(vii) CN=3, charge=−

2;

(viii) CN=2, charge=−

3; and

(ix) CN=3, charge=−

3.

22. A method according to claims 1 or 2, wherein said substrate is non-porous, wherein a sample chamber is filled with reactant gas at pressure P and each member of the array is selectively activated.

2. A method for preparing an array of activated metal-ligand compounds, comprising:

(a) providing a first metal-binding ligand and a second metal-binding ligand to first and second regions on a substrate, wherein said first and second metal-binding ligands are the same or different;

(b) providing a first metal ion to said first region and a second metal ion to said second region, wherein said first metal ion and said second metal ion are different; and

(c) providing one or more activators to said first and second regions, wherein said activators are suitable co-catalysts for polymerization, thereby forming said array.

23. A method for preparing an array of activated metal-ligand compounds, comprising:

(a) forming an array of metal-ligand compounds in respective regions of a substrate, wherein a first metal-ligand compound is in a first region on said substrate; and

a second metal-ligand compound is in a second region on said substrate, wherein said first metal-ligand and said second metal-ligand compounds are different; and

(b) providing one or more activators to said first and second regions, wherein said activators are suitable co-catalysts for polymerization, thereby forming said array.

24. The method of claim 23, wherein said wherein said first metal-ligand and said second metal-ligand compounds are different on the basis of different metal-binding ligands.

25. The process of claim 23, wherein said first metal-ligand and said second metal-ligand compounds are different on the basis of different metals.

26. The process of claim 23, wherein said one or more activators are independently selected from the group consisting of Lewis acids and ion-exchange activators.

27. The process of claim 23 wherein said first and second metal-ligand compounds are in solution and said one or more activators is in solution and said substrate comprises wells in said regions.