Fluorescent dye compounds, conjugates and uses thereof

1. A compound having a structure selected from

wherein

R 1 -R 3 and R 6 -R 16 are each independently selected from —H, halogen, heteroaryl, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR, —NO 2 , C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, substituted C 1 -C 6 alkoxy, C 1 -C 6 alkoxyaryl, substituted C 1 -C 6 alkoxyaryl, phenyl, substituted phenyl, biphenyl, substituted biphenyl, benzyl, substituted benzyl, benzoyl, substituted benzoyl, wherein R is selected from C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 1 -C 6 alkoxy, substituted C 1 -C 6 alkoxy, C 1 -C 6 alkoxyaryl, substituted C 1 -C 6 alkoxyaryl, phenyl, substituted phenyl, biphenyl, substituted biphenyl, benzyl, substituted benzyl, benzoyl, and substituted benzoyl; and

R 4 and R 5 taken separately are selected from C 1 -C 6 alkyl and C 1 -C 6 substituted alkyl, R 4 and R 5 taken together are selected from C 3 -C 7 cycloalkyl, C 4 -C 7 unsaturated cycloalkyl, C 3 -C 7 substituted cycloalkyl and C 4 -C 7 substituted unsaturated cycloalkyl;

wherein or and R 6 -R 16 is —SO 3 H;

with the proviso that if the compound comprises the structure (I), then at least one of R 1 , R 2 , R 3 or R 8 is not —H.

2. The compound of claim 1 , wherein R 6 and R 7 are each independently selected from fluorine, chlorine and bromine.

3. The compound of claim 2 , wherein R 6 and R 7 are fluorine.

4. The compound of claim 2 , wherein R 6 and R 7 are chlorine.

5. The compound of claim 2 , wherein R 6 and R 7 are bromine.

6. The compound of claim 1 , wherein R 6 is —H and R 7 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , and —CH 2 NHR.

7. The compound of claim 1 , wherein R 6 is —H and R 7 is selected from —H, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 NH 2 , and —CH 2 NHR.

8. The compound of claim 1 , having structure (I), wherein R 6 and R 7 are each independently selected from fluorine, chlorine and bromine and R 2 is selected from —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 .

9. The compound of any one of claims 1 - 8 , wherein the compound has the structure (I) and R 2 is selected from —SO 3 H, —SO 3 R, —CH 2 NH 2 , —CH 2 NHR, and —NO 2 .

10. The compound of any one of claims 1 - 8 , wherein the compound has the structure (I) and R 2 is selected from —SO 3 H and —SO 3 R.

11. The compound of any one of claims 1 - 8 , wherein the compound has the structure (I) and R 2 is selected from —CH 2 NH 2 and —CH 2 NHR.

12. The compound of claim 9 , wherein R 2 is —SO 3 H.

13. The compound of claim 9 , wherein R 2 is —SO 3 R.

14. The compound of claim 9 , wherein R 2 is —CH 2 NH 2 .

15. The compound of claim 9 , wherein R 2 is —CH 2 NHR.

16. The compound of any one of claims 1 - 8 , wherein R is

17. The compound of any one of claims 1 , 6 or 7 , wherein the compound has the structure (I), R 7 is —SO 3 H and R 2 is —CH 2 NH 2 .

18. The compound of any one of claims 1 , 6 or 7 , wherein the compound has the structure (I), R 7 is —SO 3 H and R 2 is —CH 2 NHR.

19. The compound of claim 18 , wherein R is substituted benzoyl.

20. The compound of claim 19 , wherein R is

21. The compound of any one of claims 1 - 8 , wherein R 4 and R 5 are methyl.

22. The compound of any one of claims 1 - 8 , wherein R 1 and R 3 are —H.

23. The compound of claim 1 , having structure (II), wherein R 9 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 and R 8 -R 10 are —H.

24. The compound of claim 23 , wherein R 9 is selected from —SO 3 H, —SO 3 R, —CH 2 NH 2 , —CH 2 NHR, and —NO 2 .

25. The compound of claim 23 , wherein R 9 is selected from —SO 3 H and —SO 3 R.

26. The compound of claim 23 , wherein R 9 is selected from —CH 2 NH 2 and —CH 2 NHR.

27. The compound of claim 23 , wherein R 9 is —SO 3 H.

28. The compound of claim 23 , wherein R 9 is —SO 3 R.

29. The compound of claim 23 , wherein R 9 is —CH 2 NH 2 .

30. The compound of claim 23 , wherein R 9 is —CH 2 NHR.

31. The compound of any one of claims 23 - 26 , 28 or 30 , wherein R is

32. The compound of claim 6 , having structure (II), wherein R 9 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 and R 10 -R 12 are —H.

33. The compound of claim 32 , wherein R 7 is —SO 3 H and R 9 is —CH 2 NH 2 .

34. The compound of claim 32 , wherein R 7 is —SO 3 H and R 9 is —CH 2 NHR.

35. The compound of claim 32 , wherein R is

36. The compound of any claim 1 , having structure (II), wherein R 10 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 , R 9 and R 11 -R 12 are —H.

37. The compound of claim 36 , wherein R 10 is selected from —SO 3 H, —SO 3 R, —CH 2 NH 2 , —CH 2 NHR, and —NO 2 .

38. The compound of claim 36 , wherein R 10 is selected from —SO 3 H and —SO 3 R.

39. The compound of claim 36 , wherein R 10 is selected from —CH 2 NH 2 and —CH 2 NHR.

40. The compound of claim 36 , wherein R 10 is —SO 3 H.

41. The compound of claim 36 , wherein R 10 is —SO 3 R.

42. The compound of claim 36 , wherein R 10 is —CH 2 NH 2 .

43. The compound of claim 36 , wherein R 10 is —CH 2 NHR.

44. The compound of any one of claims 36 - 39 , 41 or 43 , wherein R is

45. The compound of claim 6 , having structure (II), wherein R 10 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 and R 3 , R 9 and R 11 -R 12 are —H.

46. The compound of claim 45 , wherein R 7 is —SO 3 H and R 10 is —CH 2 NH 2 .

47. The compound of claim 45 , wherein R 7 is —SO 3 H and R 10 is —CH 2 NHR.

48. The compound of claim 47 , wherein R is

49. The compound of claim 1 , having structure (II), wherein R 11 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 , R 9 -R 10 and R 12 are —H.

50. The compound of claim 49 , wherein R 11 is selected from —SO 3 H, —SO 3 R, —CH 2 NH 2 , —CH 2 NHR, and —NO 2 .

51. The compound of claim 49 , wherein R 11 is selected from —SO 3 H and —SO 3 R.

52. The compound of claim 49 , wherein R 11 is selected from —CH 2 NH 2 and —CH 2 NHR.

53. The compound of claim 49 , wherein R 11 is —SO 3 H.

54. The compound of claim 49 , wherein R 11 is —SO 3 R.

55. The compound of claim 49 , wherein R 11 is —CH 2 NH 2 .

56. The compound of claim 49 , wherein R 11 is —CH 2 NHR.

57. The compound of any one of claims 49 - 52 , 54 or 56 , wherein R is

58. The compound of claim 6 , having structure (II), wherein R 11 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 , R 9 -R 10 and R 12 are —H.

59. The compound of claim 58 , wherein R 7 is —SO 3 H and R 11 is —CH 2 NH 2 .

60. The compound of claim 58 , wherein R 7 is —SO 3 H and R 11 is —CH 2 NHR.

61. The compound of claim 60 , wherein R is

62. The compound of claim 1 , having structure (II), wherein R 12 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 and R 9 -R 11 are —H.

63. The compound of claim 62 , wherein R 12 is selected from —SO 3 H, —SO 3 R, —CH 2 NH 2 , —CH 2 NHR, and —NO 2 .

64. The compound of claim 62 , wherein R 12 is selected from —SO 3 H and —SO 3 R.

65. The compound of claim 62 , wherein R 12 is selected from —CH 2 NH 2 and —CH 2 NHR.

66. The compound of claim 62 , wherein R 12 is —SO 3 H.

67. The compound of claim 62 , wherein R 12 is —SO 3 R.

68. The compound of claim 62 , wherein R 12 is —CH 2 NH 2 .

69. The compound of claim 62 , wherein R 12 is —CH 2 NHR.

70. The compound of any one of claims 62 - 65 , 67 or 69 , wherein R is

71. The compound of claim 6 , having structure (II), wherein R 12 is selected from —H, —CO 2 H, —CO 2 R, —SO 3 H, —SO 3 R, —CH 2 CO 2 H, —CH 2 CO 2 R, —CH 2 SO 3 H, —CH 2 SO 3 R, —CH 2 NH 2 , —CH 2 NHR and —NO 2 , and R 3 and R 9 -R 11 are —H.

72. The compound of claim 71 , wherein R 7 is —SO 3 H and R 12 is —CH 2 NH 2 .

73. The compound of claim 71 , wherein R 7 is —SO 3 H and R 12 is —CH 2 NHR.

74. The compound of claim 73 , wherein R is

75. The compound of any one of claims 23 , 32 , 36 , 45 , 49 , 58 , 62 or 71 , wherein R 9 -R 12 are H.

76. The compound of any one of claims 23 , 32 , 36 , 45 , 49 , 58 , 62 or 71 , wherein R 4 and R 5 are methyl.

77. The compound according to any one of claims 1 - 8 , wherein R 2 and R 3 are —NO 2 and R 4 and R 5 are methyl.

78. The compound according to any one of claims 1 , 6 or 7 , having structure (III) and R 1 and R 3 are —H.

79. The compound of claim 78 , wherein R 6 is —H.

80. The compound according to claim 78 , wherein R 13 , R 15 and R 16 are —H.

81. The compound of claim 80 , wherein R 2 is —SO 3 H.

82. The compound of claim 80 , wherein R 2 is —H.

83. The compound according to claim 80 , wherein R 14 is —CH 2 NH 2 .

84. The compound according to any one of claims 80 - 82 , wherein R 14 is —CH 2 NHR.

85. The compound of claim 84 , wherein R is

86. The compound of claim 81 , wherein R 14 is —H.

87. The compound of claim 80 , wherein R 14 is —SO 3 H.

88. The compound of claim 80 , wherein R 14 is —H.

89. The compound according to claim 80 , wherein R 2 is —CH 2 NH 2 .

90. The compound according to claim 80 , wherein R 2 is —CH 2 NHR.

91. The compound of claim 90 , wherein R is

92. The compound of claim 87 , wherein R 2 is —H.

93. The compound according to claim 89 , wherein R 4 and R 5 are methyl.

94. The compound according to any one of claims 1 , 6 or 7 , wherein the compound has structure (IV).

95. The compound of claim 94 , wherein R 14 is —SO 3 H.

96. The compound of claim 94 , wherein R 14 is —H.

97. The compound according to claim 94 , wherein R 10 is —CH 2 NH 2 .

98. The compound according to claim 94 , wherein R 10 is —CH 2 NHR.

99. The compound of claim 98 , wherein R is

100. The compound according to claim 94 , wherein R 14 is —H.

101. The compound according to claim 94 , wherein R 3 , R 6 , R 9 , R 11 , R 12 , R 13 , R 15 and R 16 are —H.

102. The compound according to claim 94 , wherein R 4 and R 5 are methyl.

103. A compound of claim 1 having the structure:

104. A compound of claim 1 having the structure:

105. A compound of claim 1 having the structure:

106. A compound of claim 1 having the structure

wherein R 6 and R 7 are each independently hydrogen, fluorine, chlorine or bromine.

107. A compound of claim 1 having the structure:

wherein R 6 and R 7 are each independently hydrogen, fluorine, chlorine or bromine.

108. A compound of claim 1 having the structure:

wherein R 6 and R 7 are each independently hydrogen, fluorine, chlorine or bromine.

109. A compound of claim 1 having the structure:

wherein R 6 and R 7 are each independently hydrogen, fluorine, chlorine or bromine.

110. A compound of claim 1 having the structure:

111. A compound of claim 1 having the structure:

112. A compound of claim 1 having the structure:

113. A compound of claim 1 having the structure:

114. The compound of claim 82 , wherein R14 is H.