High performance luminescent compounds
View Patent ↗Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to novel near-infrared dyes that are photostable and resistant to quenching. The dyes belong to a novel family of squaraine rotaxanes, and they are particularly well-suited for use in biological applications. Also disclosed are methods of synthesizing the dyes and methods of using the dyes.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 , R 2 , and R 3 are each independently alkyl, phenyl, polyethylene glycol, alkyl-phosphonate, alkyl-sulfonate, methylene-triazole-alkyl-sulfonate, methylene-triazole-alkyl-phosphonate, methylene-triazole-methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate;
X=alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alky alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetamido;
Y 1 and Y 2 are each independently H, alkoxy-triazole-methylene-sulfonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-sulfonate, alkoxy-triazole-methylene-phosphonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-phosphonate, triazole-methylene-sulfonate, triazole-methylene-phosphonate; triazole-methylene-dimethylammonium-alkyl-sulfonate, triazole-methylene-methylene-dimethylammonium-alkyl-phosphonate, alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alky alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetam;
Z 1 and Z 2 are each independently CH or N; and
W 1 , W 2 , W 3 , and W 4 are each independently H or OH, at least one of W 1 , W 2 , W 3 , and W 4 being OH.
2. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
3. The compound of claim 2 , wherein the compound has the formula:
4. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
5. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein;
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
6. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and r are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
7. The compound of claim 6 , wherein the compound has the formula:
8. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
9. The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate; and
Z═CH or N.
10. A compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 , R 2 , and R 3 are each independently alkyl, phenyl, polyethylene glycol, alkyl-phosphonate, alkyl-sulfonate, methylene-triazole-alkyl-sulfonate, methylene-triazole-alkyl-phosphonate, methylene-triazole-methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate;
X=alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alky alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetamido;
Y 1 and Y 2 are each independently H, alkoxy-triazole-methylene-sulfonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-sulfonate, alkoxy-triazole-methylene-phosphonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-phosphonate, triazole-methylene-sulfonate, triazole-methylene-phosphonate; triazole-methylene-dimethylammonium-alkyl-sulfonate, triazole-methylene-methylene-dimethylammonium-alkyl-phosphonate, alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alkyl alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetamido; and
W 1 , W 2 , W 3 , and W 4 are each independently H or OH, at least one of W 1 , W 2 , W 3 , and W 4 being OH.
11. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin; and
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate.
12. The compound of claim 10 , wherein the compound has the formula:
13. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin; and
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate.
14. The compound of claim 13 , wherein the compound has the formula:
15. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin; and
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate.
16. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin; and
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, alkyl-phosphonate, methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate.
17. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin; and T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, or alkyl-phosphonate.
18. The compound of claim 10 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof, wherein:
X═OH, alkoxy, aryloxy, oxy-succinimide, NH-alkyl-maleimide, or NH-polyethylene glycol-biotin;
T 1 , T 2 , T 3 , T 4 , and T 5 are each independently H or a 1,2,3-triazole ring that is substituted with a group R, wherein R=polyethylene glycol, alkyl-sulfonate, or alkyl-phosphonate.
19. A compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 , R 2 , and R 3 are each independently alkyl, phenyl, polyethylene glycol, alkyl-phosphonate, alkyl-sulfonate, methylene-triazole-alkyl-sulfonate, or methylene-triazole-alkyl-phosphonate, methylene-triazole-methylene-dimethylammonium-alkyl-sulfonate, or methylene-dimethylammonium-alkyl-phosphonate;
X=alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alky alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetamido;
Y 1 and Y 2 are each independently H, alkoxy-triazole-methylene-sulfonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-sulfonate, alkoxy-triazole-methylene-phosphonate, alkoxy-triazole-methylene-dimethylammonium-alkyl-phosphonate, triazole-methylene-sulfonate, triazole-methylene-phosphonate; triazole-methylene-dimethylammonium-alkyl-sulfonate, triazole-methylene-methylene-dimethylammonium-alkyl-phosphoriate, alkyl, phenyl, alkyl-carboxylic acid, alkyl ester, alkyl hydroxysuccinimde ester, alkyl maleimide, alkyl isothiocyanate, alkyl azide, alky alkyne, alkyl haloacetamido, aryl ester, aryl hydroxysuccinimde ester, aryl maleimide, aryl isothiocyanate, aryl azide, aryl alkyne, or aryl haloacetamido; and
W 1 , W 2 , W 3 , and W 4 are each independently H or OH.