Radical polarizing agents for dynamic nuclear polarization
The present invention provides a variety of radicals, which are useful as polarizing compounds. Exemplary radicals are represented by compounds of Structural Formulae (I), (II), (III) and (IV) as described herein.
1. A compound represented by structural Formula (I):
wherein:
each R is independently —R′, —OR′, —SR′, halogen, —CN, —NO2, —NR′R″, polyethyleneglycol —COOR′, —OCOR′, —CONR′R″, or —NR′COR″, or
two R on adjacent carbon atoms taken together are
Z 1 -Z 5 are each independently —SO 2 X, —SO 3 X or —SO 2 NR′R″;
R′ and R″ are independently —H, an optionally substituted alkyl or an optionally substituted aryl;
X is a cation;
a1, b1, c1 and d1 are each integers from 0 to 4, wherein the sum of a1, b1, c1and d1 is one or greater;
a2, b2, c2 and d2 are each independently integers from 0 to 4;
e1 and e2 are each independently an integer from 0 to 5; and
j and k are independently integers from 0 to 2.
2. The compound of claim 1 , wherein Z 1 -Z 5 are each independently —SO 3 X.
3. The compound of claim 2 , wherein X includes H + , NR′R″R′″R″″, Ag + , Ca 2+ , Ba 2+ , Li + , Na + or K + or a combination thereof and wherein R′, R″R′″ and R″″ are each independently —H, an optionally substituted alkyl or an optionally substituted aryl.
4. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.
5. The compound of claim 1 , wherein the compound is represented by Structural Formula (Ia):
6. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
7. A method comprising polarizing an unpaired electron spin in a compound of claim 3 .
8. A method comprising polarizing an unpaired electron spin in a compound of claim 5 .
9. The compound of claim 5 , wherein e1 is 1.
10. A pharmaceutical composition comprising a compound of claim 9 and a pharmaceutically acceptable carrier.
11. A method comprising polarizing an unpaired electron spin in a compound of claim 9 .
12. The compound of claim 5 , wherein e1 is 0.
13. A pharmaceutical composition comprising a compound of claim 12 and a pharmaceutically acceptable carrier.
14. A method comprising polarizing an unpaired electron spin in a Compound of claim 12 .
15. The compound of claim 5 , wherein R is —COOR′, a halogen or a fluoroalkyl.
16. A pharmaceutical composition comprising a compound of claim 15 and a pharmaceutically acceptable carrier.
17. A method comprising polarizing an unpaired electron spin in a compound of claim 15 .
18. The compound of claim 5 , wherein the sum of a1, b1, c1, d1 and e1 is from 2 to 7.
19. The compound of claim 18 , wherein the compound is:
20. A pharmaceutical composition comprising a compound of claim 19 and a pharmaceutically acceptable carrier.
21. A method comprising polarizing an unpaired electron spin in a compound of claim 19 .
22. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable carrier.
23. A method comprising polarizing an unpaired electron spin in a compound of claim 18 .
24. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.
25. A method comprising polarizing an unpaired electron spin in a compound of claim 2 .
26. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
27. A method comprising polarizing an unpaired electron spin in a compound of claim 1 .
28. The method of claim 27 further comprising administering the compound to a subject for magnetic resonance imaging.
29. The method of claim 28 , wherein the subject is a human.
30. A composition comprising a compound of claim 1 .
31. The composition of claim 30 , further comprising a stable radical.
32. The composition of claim 31 , wherein the stable radical is a verdazyl, hydrazyl, nitroxide or trityl radical.