Sulfonate compounds
This disclosure relates to compounds containing a fluorophore covalently bonded to at least one protected sulfonate group of formula (I): in which X and R 2 -R 5 are defined in the specification. This disclosure also relates to use of these compounds as dyes in an imaging methods, as well as intermediates that can be used to prepare these compounds.
1. A compound, comprising:
a fluorophore covalently bonded to at least one protected sulfonate group of formula (I):
wherein
X is C(R 1 ) or N, in which R 1 is H, halo, or C 1 -C 10 alkyl;
R 3 is S—S—R a , S—R a , NO 2 , OR a , OC(O)R a , halo C 1 -C 10 alkyl, or aryl, in which R a is C 1 -C 10 alkoxy, C 1 -C 10 alkyl, or C 1 -C 20 heterocycloalkyl and is optionally substituted with NRR′, halo, OR, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, or heteroaryl, each of R and R′, independently, being H or C 1 -C 10 alkyl; and
each of R 2 , R 4 , and R 5 , independently, is H, halo, or C 1 -C 10 alkyl;
provided that, when X is CH, R 3 is not OC(O)CH 3 .
2. The compound of claim 1 , wherein R 3 is S—S—R a or NO 2 , in which R a is C 1 -C 10 alkyl optionally substituted with NRR′, each of R and R′, independently, being H or C 1 -C 10 alkyl.
3. The compound of claim 2 , wherein R 3 is S—S—R a , in which R a is CH 3 or CH 2 CH 2 N(CH 3 ) 2 .
4. The compound of claim 3 , wherein X is C(R 1 ), in which R 1 is H or F.
5. The compound of claim 4 , wherein each of R 2 , R 4 , and R 5 is H.
6. The compound of claim 1 , wherein R 3 is halo C 1 -C 10 alkyl, or aryl.
7. The compound of claim 6 , wherein R 3 is F methyl, isopropyl, or phenyl.
8. The compound of claim 7 , wherein X is C(R 1 ), in which R 1 is H or F.
9. The compound of claim 8 , wherein R 5 is H or F and each of R 2 and R 4 is H.
10. The compound of claim 1 , wherein R 3 is OC(O)R a , in which R a is C 1 -C 10 alkyl optionally substituted with halo, OR, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, or heteroaryl, R being H or C 1 -C 10 alkyl.
11. The compound of claim 10 , wherein R 3 is OC(O)R a , in which R a is methyl optionally substituted with Cl, Br, OCH 3 , or
12. The compound of claim 11 , wherein X is C(R 1 ) or N, in which R 1 is H.
13. The compound of claim 12 , wherein each of R 2 , R 4 , and R 5 is H.
14. The compound of claim 1 , wherein the fluorophore comprises a naphthalene moiety, a cyanine moiety, an oxazine moiety, a coumarin moiety, a rhodamine moiety, or a xanthene moiety, each of which is optionally substituted with C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b and R c , independently, being H or C 1 -C 10 alkyl.
15. The compound of claim 14 , wherein the fluorophore comprises a moiety selected from the group consisting of:
in which n is 1, 2, or 3, each of A and A′, independently, is a 5-7 membered ring optionally fused with at least one 5-7 membered ring, and each moiety is optionally substituted with C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b and R c , independently, being H or C 1 -C 10 alkyl.
16. The compound of claim 15 , wherein the fluorophore is
17. An imaging method, comprising:
delivering a compound of claim 1 into a cell; and
irradiating the cell with an excitation light, thereby generating fluorescence from the cell.
18. The method of claim 17 , wherein the fluorescence has a wavelength greater than about 600 nm.
19. A compound, comprising:
a fluorophore covalently bonded to at least one protected sulfonate group of formula (I):
wherein
X is C(R 1 ) or N, in which R 1 is H, halo, or C 1 -C 10 alkyl;
R 3 is H, S—S—R a , S—R a , NO 2 , OR a , OC(O)R a , halo, C 1 -C 10 alkyl, or aryl, in which R a is C 1 -C 10 alkoxy, C 1 -C 10 alkyl, or C 1 -C 20 heterocycloalkyl and is optionally substituted with NRR′, halo, OR, C 3 -C 20 cycloalkyl, C 1 -C 20 heterocycloalkyl, aryl, or heteroaryl, each of R and R′, independently, being H or C 1 -C 10 alkyl;
each of R 2 , R 4 , and R 5 , independently, is H, halo, or C 1 -C 10 alkyl; and
the fluorophore comprises a cyanine moiety, an oxazine moiety, a coumarin moiety, a rhodamine moiety, or a xanthene moiety, each of which is optionally substituted with C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b and R c , independently, being H or C 1 -C 10 alkyl;
provided that, when X is CH, R 3 is not OC(O)CH 3 .
20. The compound of claim 19 , wherein the fluorophore comprises a moiety selected from the group consisting of:
in which n is 1, 2, or 3, each of A and A′, independently, is a 5-7 membered ring optionally fused with at least one 5-7 membered ring, and each moiety is optionally substituted with C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl, heteroaryl, OR b , SR b , NR b R c , COOR b , or COR b , each R b and R c , independently, being H or C 1 -C 10 alkyl.
21. The compound of claim 20 , wherein the fluorophore is
22. The compound of claim 19 , wherein R 3 is H.
23. The compound of claim 19 , wherein X is C(R 1 ), in which R 1 is H or F.
24. The compound of claim 19 , wherein each of R 2 , R 4 , and R 5 , independently, is H or F.