Self-assembled monolayers and methods for using the same in biosensing applications
Cross-linked amphiphile constructs that form self-assembled monolayers (SAMs) on metal surfaces such as gold surfaces are disclosed. These new SAMs generate well packed and highly oriented monolayer films on gold surfaces. A method for using the SAMs in the fabrication of biomolecule sensors is also disclosed.
1. A self-assembled monolayer comprising a compound of Formula II:
wherein:
R 1 -R 4 are each, independently, SR a , OH, COR b , heterocyclyl, heteroaryl, CN, N 3 , or halo;
R 7 is 0-2 R c groups;
X, Y, U, and V are each, independently, C 2 -C 6 alkyl;
R a is H, C 1-20 alkyl, C(O)H, CO—(C 1-20 alkyl), SH, S(C 1-20 alkyl);
R b is C 0-20 hydroxyl, C 3-10 heterocycloalkyl, C 5-10 aryl, C 5-10 heteroaryl, or NR I R II ;
R c is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, hydroxyl, halo, haloalkyl, haloalkoxy, cyano, nitro, azido, amino, alkylamino, dialkylamino, carboxy, carboxyalkyl ester, carboxy aryl ester, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, sulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylsulfonyl,arylsulfinyl, alkylsulfonyl, or arylsufonyl; and
R I and R II are each, independently selected from H, substituted or unsubstituted alkyl,
or R I and R II come together to form a 4-10-membered substituted or unsubstituted heterocyclic ring.
2. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is SR a .
3. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is S(C 1-20 alkyl), SC(O)(C 1-20 alkyl), SH, or S(C 1-20 alkyl).
4. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is SH or SC(O)(C 1-20 alkyl).
5. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is SH.
6. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is SC(O)(C 1-20 alkyl).
7. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is SC(O)CH 3 .
8. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are SR a .
9. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are S(C 1-20 alkyl), SC(O)(C 1-20 alkyl), SH, or S(C 1-20 alkyl).
10. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are SH or SC(O)(C 1-20 alkyl).
11. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are SH.
12. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are SC(O)(C 1-20 alkyl).
13. The self-assembled monolayer of claim 1 , wherein R 1 and R 2 are SC(O)CH 3 .
14. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is OH, C(O)R b , N 3 , heterocyclyl, or heteroaryl.
15. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is OH.
16. The self-assembled monolayer of claim 1 , wherein at least one of R 1 , R 2 , R 3 , and R 4 is CN.
17. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are OH, C(O)R b , N 3 , heterocyclyl, or heteroaryl.
18. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are OH.
19. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are heterocyclyl or heteroaryl.
20. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are heterocyclyl.
21. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are 1,4,7-triazacyclononanyl.
22. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are heteroaryl.
23. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are pyridyl or imidazolyl.
24. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are pyridyl.
25. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are imidazolyl.
26. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are azido.
27. The self-assembled monolayer of claim 1 , wherein R 3 and R 4 are CN.
28. The self-assembled monolayer of claim 1 , wherein R 7 is 0 Rc groups.
29. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are OH;
X, Y, U, and V are C 4 alkyl; and
R 7 is absent.
30. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are OH or N 3 ;
X, Y, U, and V are C 2-6 a 1 kyl; and
R 7 is absent.
31. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are N 3 ;
X, Y, U, and V are C 2-6 alkyl; and
R 7 is absent.
32. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are N 3 ;
X, Y, U, and V are C 5 alkyl; and
R 7 is absent.
33. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are OH or N 3 ;
X, Y, U, and V are C 5 alkyl; and
R 7 is absent.
34. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are imidazolyl;
X, Y, U, and V are C 4 alkyl; and
R 7 is absent.
35. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—(C 1-20 alkyl);
R 3 and R 4 are imidazolyl;
X, Y, U, and V are C 4 alkyl; and
R 7 is absent.
36. The self-assembled monolayer of claim 1 , wherein:
R 1 and R 2 are SH or SCO—C 3 alkyl;
R 3 and R 4 are imidazolyl;
X and Y are each C 2 alkyl;
U and V are each C 6 alkyl; and
R 7 is absent.
37. The self-assembled monolayer of claim 1 , wherein at least one of R 3 or R 4 is C(O)R b .
38. The self-assembled monolayer of claim 37 , wherein R b is NR I R II .
39. The self-assembled monolayer of claim 38 , wherein NR I R II is a triazacyclononane group.
40. The self-assembled monolayer of claim 39 , wherein the triazacyclononane group is substituted with an alkylcarboxylate.
41. The self-assembled monolayer of claim 38 , wherein NR I R II is NH(C 1-20 alkyl).
42. The self-assembled monolayer of claim 41 , wherein the NH(C 1-20 alkyl) is substituted with a nitrilotriacetic acid.
43. The self-assembled monolayer of claim 1 , wherein the compound is selected from:
2,2′-(4,5-bis(6-mercaptohexyl)-1,2-phenylene)diethanol;
((4,5-bis(2-hydroxyethyl)-1,2-phenylene)bis(hexane-6,1-diyl)) diethanethioate;
5,5′-(4,5-bis(6-mercaptohexyl)-1,2-phenylene)bis(pentan-1-ol);
((4,5-bis(5-hydroxypentyl)-1,2-phenylene)bis(hexane-6,1-diyl)) diethanethioate;
6,6′-(4,5-bis(pyridin-2-ylethynyl)-1,2-phenylene)bis(hex-5-yne-1-thiol);
((4,5-bis(pyridin-2-ylethynyl)-1,2-phenylene)bis(hex-5-yne-6,1-diyl)) diethanethioate;
4,4′-(4,5-bis(4-mercaptobutyl)-1,2-phenylene)bis(butan-1-ol);
((4,5-bis(4-hydroxybutyl)-1,2-phenylene)bis(butane-4,1-diyl)) diethanethioate;
2-(2-(2-azidoethyl)-4,5-bis(6-mercaptohexyl)phenyl)ethanol;
((4-(2-azidoethyl)-5-(2-hydroxyethyl)-1,2-phenylene)bis(hexane-6,1-diyl)) diethanethioate;
6,6′-(4,5-bis(2-azidoethyl)-1,2-phenylene)bis(hexane-1-thiol);
((4,5-bis(2-azidoethyl)-1,2-phenylene)bis(hexane-6,1-diyl)) diethanethioate;
(4,5-bis(5-azidopentyl)-1,2-phenylene)bis(pentane-1-thiol);
((4,5-bis(5-azidopentyl)-1,2-phenylene)bis(pentane-5,1-diyl)) diethanethioate;
5-(2-(5-azidopentyl)-4,5-bis(5-mercaptopentyl)phenyl)pentan-1-ol;
((4-(5-azidopentyl)-5-(5-hydroxypentyl)-1,2-phenylene)bis(pentane-5,1-diyl)) diethanethioate;
4,4′-(4,5-bis(4-(1H-imidazol-1-yl)butyl)-1,2-phenylene)bis(butane-1-thiol);
((4,5-bis(4-(1H-imidazol-1-yl)butyl)-1,2-phenylene)bis(butane-4,1-diyl)) diethanethioate;
2,2′-(4,5-bis(6-(1H-imidazol-1-yl)hexyl)-1,2-phenylene)diethanethiol;
S,S′-((4,5-bis(6-(1H-imidazol-1-yl)hexyl)-1,2-phenylene)bis(ethane-2,1-diyl)) diethanethioate;
5,5′-(4,5-bis(5-mercaptopentyl)-1,2-phenylene)bis(pentan-1-ol);
((4,5-bis(5-hydroxypentyl)-1,2-phenylene)bis(pentane-5,1-diyl)) diethanethioate;
6,6′-(4,5-bis(2-(1H-imidazol-1-yl)ethyl)-1,2-phenylene)bis(hexane-1-thiol); and
((4,5-bis(2-(1H-imidazol-1-yl)ethyl)-1,2-phenylene)bis(hexane-6,1-diyl)) diethanethioate.
44. The self-assembled monolayer of claim 1 , wherein the compound is attached to a metal surface.
45. The self-assembled monolayer of claim 44 , wherein the metal surface comprises gold.
46. The self-assembled monolayer of claim 44 , wherein at least one of R 1 , R 2 , R 3 and R 4 is SR a and wherein the compound attaches to the metal surface via a thiol-metal bond.
47. A kit for detecting one or more target molecules in a sample, which comprises the self-assembled monolayer of claim 1 .