Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds
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.
1. A compound 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 ;
each R 3 and R 4 independently represents hydrogen or an organic group; and
R 8 represents an organic group.
2. The compound of claim 1 wherein R 8 represents a biomolecule.
3. The compound of claim 2 wherein the biomolecule is selected from the group consisting of peptides, proteins, glycoproteins, nucleic acids, lipids, saccharides, oligosaccharides, polysaccharides, and combinations thereof.
4. The compound of claim 1 wherein each R 1 represents hydrogen.
5. The compound of claim 1 wherein each R 2 represents hydrogen.
6. The compound of claim 1 wherein R 3 comprises a covalently bound organic dye.
7. The compound of claim 6 wherein the organic dye is a fluorescent dye.
8. A compound 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 CHOR 3 ;
R 3 represents —C(O)Z, wherein:
Z represents an alkyl group, OR 6 , or NHR 7 ;
R 6 is selected from the group consisting of an alkyl group, an aryl group, an alkaryl group, and an aralkyl group;
R 7 is a biotinylation product of a primary amine-containing organic group; and
R 8 represents an organic group.
9. The compound of claim 8 wherein the biotinylation product is the biotinylation product of a primary amine-containing group of the formula —(CH 2 CH 2 O) b (CH 2 ) c -L d -(CH 2 CH 2 O) e (CH 2 ) f NH 2 and/or —(CD 2 CD 2 O) b (CD 2 ) c -L d -(CD 2 CD 2 O) e (CD 2 ) f NH 2 , wherein b=0 to 100; c=0 to 100; d=0 to 100; e=0 to 100; f=0 to 100; and L is an optional cleavable linker.
10. The compound of claim 9 wherein the cleavable linker, if present, is a disulfide.
11. A compound 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 polymeric or a copolymeric group;
R 4 independently represents hydrogen or an organic group; and
R 8 represents an organic group.
12. The compound of claim 11 wherein the copolymeric group comprises a hydrophilic segment and a hydrophobic segment.
13. The compound of claim 11 wherein the copolymeric group comprises a fragment of the formula —[CH 2 CH 2 O] n —[C(O)(CH 2 ) 5 O] m —H, wherein n=0 to 100 and m=0 to 100.
14. A dibenzocyclooctyne having a biotin fragment attached thereto.
15. A compound of the formula:
wherein:
each R 1 and R 2 is hydrogen;
X represents CHOR 3 ;
R 3 represents an organic group comprising a biotin fragment; and
R 8 represents an organic group.
16. A dibenzocyclooctyne having a covalently bound organic dye attached thereto.
17. A compound of the formula:
wherein:
each R 1 and R 2 is hydrogen;
X represents CHOR 3 ;
R 3 represents an organic group comprising a covalently bound organic dye; and
R 8 represents an organic group.
18. A dibenzocyclooctyne having a nanoparticle attached thereto.
19. A method of preparing a heterocyclic compound, the method comprising:
combining at least one azide-functional compound with at least one dibenzocyclooctyne according to claim 18 ; and
allowing the at least one azide-functional compound and the at least one alkyne to react under conditions effective to form the heterocyclic compound.
20. A compound 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═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ;
R 3 represents an organic group attached to a nanoparticle;
R 4 represents hydrogen or an organic group; and
R 8 represents an organic group.
21. A compound of the formula:
wherein:
each R 1 and R 2 is hydrogen;
X represents CHOR 3 ;
R 3 represents an organic group; and
R 8 represents an organic group.