Methods for the preparation and characterization of multi-substituted fullerenes

• US 6,448,412 B1
• Filed: 10/30/2000
• Issued: 09/10/2002
• Est. Priority Date: 07/31/1995
• Status: Expired due to Term

• Current Assignee: Luna Innovations, Inc.
• Original Assignee: Sphere Biosystems, Inc.
• Inventors: Wilson, Stephen R., Murphy, Randall B., Lu, Quing
• Primary Examiner(s): Lambkin, Deborah C.
• Application Number:
  US09/702,144
• Time in Patent Office: 680 Days
• Field of Search: 548/417, 548/460, 556/482, 560/8, 560/124, 562/363, 562/308, 562/579, 562/630, 568/632, 549/416, 549/432, 549/439, 558/388
• US Class Current: 506/15
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: C07C 2604/00 Fullerenes, e.g. C60 buckminsterfullerene or C70
• CPC Class Codes: C07C 61/00 Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07D 209/58 [b]- or [c]-condensed
• CPC Class Codes: C07D 213/16 containing only one pyridine ring
• CPC Class Codes: C07D 317/72 spiro-condensed with carbocyclic rings
• CPC Class Codes: C07D 333/08 Hydrogen atoms or radicals containing only hydrogen and carbon atoms
• CPC Class Codes: C07D 487/06 Peri-condensed systems
• CPC Class Codes: C40B 40/04 Libraries containing only organic compounds
• CPC Class Codes: C40B 50/08 Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
• 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: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 comprising bio-molecules
• CPC Class Codes: G11C 13/025 using fullerenes, e.g. C60, or nanotubes, e.g. carbon or silicon nanotubes
• CPC Class Codes: Y10S 977/734 Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
• CPC Class Codes: Y10S 977/835 Chemical or nuclear reactivity/stability of composition or compound forming nanomaterial
• CPC Class Codes: Y10S 977/842 for carbon nanotubes or fullerenes
• CPC Class Codes: Y10S 977/881 Microscopy or spectroscopy, e.g. sem, tem

Abstract

The invention is directed to multiply-substituted fullerene derivatives of novel configurations, and methods for their preparation and use. The methods involve the combinatorial synthesis of a library of fullerene derivatives and comprises the steps of forming a mixture of fullerene derivatives by reacting the C_n fullerene with two or more reactive precursor compounds, and removing the unreacted compounds to yield the fullerene derivatives having the desired activity. Methods for the identification and screening of a combinatorial library of fullerenes by ³He-nuclear magnetic resonance and electrospray mass spectrometry to define members with the optimal desired activity are also provided.

Claims

1. A method for the simultaneous synthesis of a multiplicity of different multiply-substituted fullerenes having the formula:

wherein;

Z₁, Z₂ and Z₃ are absent or present, provided that at least one is present, and are independently selected from the group consisting of —

CR₁R₂—

, —

CR₁R₂—

CR₃R₄—

, —

NR₁—

, —

O—

CR₁R₂—

, —

S—

CR₁R₂—

, —

NR₁—

CR₂R₃—

, —

R₁R₂C—

NR₃—

CR₄R₅—

, —

R₁C═

N—

CR₂R₃—

, —

R₁R₂C—

NR₃—

NR₄—

, —

R₁R₂C—

NR₃—

O—

, —

N═

NR₁—

, —

N═

N—

NR₁—

, —

N═

N—

CR₁R₂—

, —

O—

NR₁—

O—

, —

R₁R₂C—

O—

CR₃R₄—

, —

R₁R₂C—

O—

NR₃—

, —

R₁C═

N—

NR₂—

, —

R₁C═

N—

O—

, —

R₁N—

NR₂—

NR₃—

, —

R₁N—

NR₂—

O—

, —

CR₁R₂—

CR₃R₄—

CR₅R₆—

, —

CR₁R₂—

CR₃═

CR₄—

, —

CR₁R₂—

CR₃R₄—

CR₅CR₆—

CR₇R₈—

, —

CR₁═

R₂—

CR₃R₄—

CR₅R₆—

, —

CR₁R₂—

CR₃═

CR₄—

CR₅R₆—

, —

CR₁═

CR₂—

CR₃═

CR₄— and

—

CR₁R₂—

CR₃═

C═

CR₄—

such that Z₁, Z₂ and Z₃ are each attached to the carbon skeleton of the fullerene structure by two single bonds selected from the group consisting of a carbon—

carbon bond, a carbon-oxygen bond, a carbon-sulfur bond, and a carbon-nitrogen bond, the unsatisfied valences of each Z moiety being the location of those bonds;

R₁, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ are the same or different and are selected from the group consisting of hydrogen, oxygen lower alkyl, higher alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, carboxylic acids, carboxylic esters, alkylthio, thioalkyl, aryl, aryloxy, aralkyl, primary amine, secondary amine, amino acid side chains, and heterocycles, such that C together with any two R groups bonded thereto forms an oxo or thioxo group, hydrocarbon ring or heterocycle;

Y₁ and Y₂ are absent or present, providing that at least one is present, and are selected from the group consisting of hydrogen, lower alkyl, higher alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, thioalkyl, aryl, aryloxy, aralkyl, primary amine, secondary amine, amino acid side chains, and heterocycles;

20<

n<

240;

(k₁+k₂) is 1 to n; and

(m₁+m₂+m₃) is 1 to n/2, with the limitation that 2(m₁+m₂+m₃)+(k₁+k₂)≦

n;

or a salt or addition compound thereof;

said method comprising the steps of;

(a) reacting fullerenes of the formula C_n, wherein 20<

n<

240, with a plurality of first compounds selected from compounds which react with the fullerenes to form a plurality of fullerene monoadducts, wherein the reaction adds to the fullerenes either (i) moieties Z₁ or (ii) moieties selected from the group consisting of Y₁, Y₂, and Y₁ and Y₂, and

(b) reacting said fullerene monoadducts with a plurality of second compounds selected from compounds which react with the fullerene monoadducts to form a plurality of fullerene diadducts, wherein the reaction adds to the fullerene monoadducts the other of (i) moieties Z₁ or (ii) moieties selected from the group consisting of Y₁, Y₂, and Y₁ and Y₂ than was added in step (a), and

(c) reacting said fullerene diadducts with plurality of third compounds is selected from compounds which react with the fullerene diadducts to form a plurality of fullerene triadducts, wherein the reaction adds to the fullerene diadducts moieties Z₂.

2. The method of claim 1 wherein at least one of said compounds contains an unreactive protective moiety.

3. A library of multiply-substituted fullerene compounds produced by the method of claim 1.

5. The method of claim 3 wherein at least one of said compounds contains an unreactive protective moiety.

6. A library of multiply-substiputed fullerene compounds produced by the method of claim 3.

8. The method of claim 1, further comprising

(c) reacting said fullerene diadducts with a plurality of fourth compounds selected from compounds which react with the fullerene diadducts to form a plurality of fullerene triadducts, wherein the reaction adds to the fullerene diadducts moieties Z₃.

4. A method for the simultaneous synthesis of a multiplicity of different multiply-substituted fullerenes having the formula:

wherein

Z₄, Z₅ and Z₆ are absent or present, provided that at least two are present, and are independently selected from the group consisting of —

CR₉R₁₀—

, —

CR₉R₁₀—

CR₁₁R₁₂—

, —

NR₉—

, —

O—

CR₉R₁₀—

, —

S—

CR₉R₁₀—

, —

NR₉—

CR₁₀R₁₁—

, —

R₉R₁₀C—

NR₁₁—

CR₁₂R₁₃—

, —

R₉C═

N—

CR₁₀R₁₁—

, —

R₉R₁₀C—

NR₁₁—

NR₁₂—

, —

R₉R₁₁C—

NR₁₁—

O—

, —

N═

NR₉—

, —

N—

N═

NR₉—

, —

N═

N—

CR₉R₁₀—

, —

O—

NR₉—

O—

, —

R₉R₁₀C—

O—

CR₁₁R₁₂—

, —

R₉R₁₀C—

O—

NR₁₁—

, —

R₉C═

N—

NR₁₀—

, —

R₉C═

N—

O—

, —

R₉N—

NR₁₀—

NR₁₁—

, —

R₉N—

NR₁₀—

O—

, —

CR₉R₁₀—

CR₁₁R₁₂—

CR₁₃R₁₄—

, —

CR₉R₁₀—

CR₁₁═

CR₁₂—

, —

CR₉R₁₀—

CR₁₁R₁₂—

CR₁₃CR₁₄—

CR₁₅R₁₆—

, —

CR₉═

R₁₀—

CR₁₁R₁₂—

CR₁₃R₁₄—

, —

CR₉R₁₀-CR₁₁═

CR₁₂—

CR₁₃R₁₄—

, —

CR₉═

CR₁₀—

CR₁₁═

CR₁₂— and

—

CR₉R₁₀-CR₁₁═

C═

CR₁₂—

, such that Z₄, Z₅ and Z₆ are each attached to the carbon skeleton of the fullerene structure by two single bonds selected from the group consisting of a carbon-bond, a carbon-oxygen bond, a carbon-sulfur bond and a carbon-nitrogen bond, the unsatisfied valances of each Z moiety being the location of those bonds;

R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅ and R₁₆ are the same or different and are selected from the group consisting of hydrogen, oxygen, lower alkyl, higher alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, carboxylic acids, carboxylic esters, alkylthio, thioalkyl, aryl, aryloxy, aralkyl, primary amine, secondary amine, amino acid side chains, and heterocycles, such that C together with any two R groups bonded thereto forms an oxo or thioxo group, hydrocarbon ring or heterocycle;

20<

n<

240; and

(m₄+m₅+m₆) is 2 to n/2;

or a salt or addition compound thereof,

said method comprising the steps of;

(a) reacting fullerenes of the formula C_n, wherein 20<

n<

240, with a plurality of first compounds selected from compounds which react with the fullerenes to form a plurality of fullerene monoadducts, wherein the reaction adds to the fullerenes moieties Z₄; and

(b) reacting said fullerene monoadducts with a plurality of second compounds selected from compounds which react with the fullerene monoadducts to form a plurality of fullerene diadducts, wherein the reaction adds to the fullerene monoadducts moieties Z₅.

7. The method of claim 4 further comprising the step of reacting said fullerenes with a third compound containing the moiety Z₆.

9. The method of claim 4, further comprising

(c) reacting said fullerene diadducts with a plurality of third compounds selected from compounds which react with the fullerene diadducts to form a plurality of fullerene triadducts, wherein the reaction adds to the fullerene diadducts moieties Z₆.