Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds

Patent metadata

Field	Value
Publication number	US-2016159732-A1
Application number	US-201514967896-A
Country	US
Kind code	A1
Filing date	Dec 14, 2015
Priority date	Nov 21, 2007
Publication date	Jun 9, 2016
Grant date	—

Abstract

1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

First claim

What is claimed is:

1 . An alkyne of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ;
R 3 represents a covalently bound fluorescent organic dye; and
R 4 represents hydrogen or an organic group.

2 . The alkyne of claim 1 wherein each R 1 represents hydrogen.

3 . The alkyne of claim 1 wherein each R 2 represents hydrogen.

4 . A composition comprising a blend of:
an alkyne and a copolymer comprising a hydrophilic segment and a hydrophobic segment, wherein the alkyne is of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 and R 4 independently represents hydrogen or an organic group.

5 . The composition of claim 4 wherein the copolymer is of the formula R 9 O—[CH 2 CH 2 O] p —[C(O)(CH 2 ) 5 O] o —H, wherein R 9 represents an alkyl group, p=0 to 100, and o=0 to 100.

6 . The composition of claim 5 wherein R 9 represents methyl.

7 . A substrate in the form of a resin, a gel, nanoparticles, or combinations thereof, wherein the substrate has on the surface thereof an alkyne of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 and R 4 independently represents hydrogen or an organic group.

8 . The substrate of claim 7 wherein the X group of the alkyne represents a point of attachment to the surface of the substrate.

9 . A substrate comprising a three-dimensional matrix and having on the surface thereof an alkyne of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 and R 4 independently represents hydrogen or an organic group.

10 . The substrate of claim 9 wherein the X group of the alkyne represents a point of attachment to the surface of the substrate.

11 . A method of immobilizing a biomolecule on a substrate, the method comprising:
providing a substrate according to claim 7 ; and contacting the substrate with a 1,3-dipole-functional biomolecule under conditions effective to form a heterocyclic compound.

12 . The method of claim 11 wherein the 1,3-dipole-functional biomolecule is selected from the group consisting of an azide-functional biomolecule, a nitrile oxide-functional biomolecule, a nitrone-functional biomolecule, an azoxy-functional biomolecule, an acyl diazo-functional biomolecule, and combinations thereof.

13 . The method of claim 11 wherein the biomolecule is selected from the group consisting of peptides, proteins, glycoproteins, nucleic acids, lipids, saccharides, oligosaccharides, polysaccharides, and combinations thereof.

14 . A method of immobilizing a biomolecule on a substrate, the method comprising:
providing a substrate according to claim 9 ; and contacting the substrate with a 1,3-dipole-functional biomolecule under conditions effective to form a heterocyclic compound.

15 . The method of claim 14 wherein the 1,3-dipole-functional biomolecule is selected from the group consisting of an azide-functional biomolecule, a nitrile oxide-functional biomolecule, a nitrone-functional biomolecule, an azoxy-functional biomolecule, an acyl diazo-functional biomolecule, and combinations thereof.

16 . The method of claim 14 wherein the biomolecule is selected from the group consisting of peptides, proteins, glycoproteins, nucleic acids, lipids, saccharides, oligosaccharides, polysaccharides, and combinations thereof.

17 . An article comprising an immobilized biomolecule prepared by the method of claim 11 .

18 . An article comprising an immobilized biomolecule prepared by the method of claim 14 .

19 . An article comprising a protein immobilized on a three-dimensional matrix.

Assignees

• Univ Georgia

Inventors

• Boons Geert-Jan
• Guo Jun
• Ning Xinghai
• Wolfert Margaretha

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61K49/0052

  Small organic molecules (oligomers, polymers, dendrimers A61K49/0054) · CPC title

• A61K49/0021 Primary

  the fluorescent group being a small organic molecule · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• C07D311/90

  with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9 · CPC title