Optically pure and enriched isomers of chelating ligands and contrast agents

1. A composition comprising a metal chelate having a structure:

said composition having an enantiomeric excess of greater than 50% of an (R) isomer of said chelate at the 2 position, wherein n can range from 1 to 4, and wherein M can be selected from the group consisting of Gd(III), Fe(III), Mn(II), Mn(III), Cr(III), Cu(II), Dy(III), Ho(III), Er(III), Eu(III), Tb(II), Tb(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV); and wherein said chelate is conjugated optionally through a linker to one or more TBMs, wherein said TBM is a peptide.

2. A composition comprising a metal chelate having a structure:

said composition having an enantiomeric excess of greater than 50% of an (S) isomer of said chelate at the 2 position, wherein n can range from 1 to 4, and wherein M can be selected from the group consisting of Gd(III), Fe(III), Mn(II), Mn(III), Cr(III), Cu(II), Dy(III), Ho(III), Er(III), Eu(III), Tb(II), Tb(III), Ce(III), Pr(III), Yb(III), Tm(III), Nd(III), and Tb(IV); and wherein said chelate is conjugated optionally through a linker to one or more TBMs, wherein said TBM is a peptide.

3. The composition of claim 1 , wherein said composition has an enantiomeric excess of greater than 85% of the (R) isomer at the 2 position.

4. The composition of claim 2 , wherein said composition has an enantiomeric excess of greater than 85% of the (S) isomer at the 2 position.

5. The composition of claim 1 , wherein said composition has an enantiomeric excess of about 97% or more of the (R) isomer at the 2 position.

6. The composition of claim 2 , wherein said composition has an enantiomeric excess of about 97% or more of the (S) isomer at the 2 position.

7. The composition of any one of claim 1 or 2 , wherein said TBM is linked by a linker to the metal chelate.

8. The composition of claim 1 or 2 , wherein a ratio of TBM to metal chelate in said composition can be from about 1:8 to about 8:1.

9. The composition of claim 8 , wherein said ratio of TBM to metal chelate is about 1:4.

10. The composition of claim 8 , wherein said ratio of TBM to metal chelate is about 2:2.

11. The composition of claim 1 or 2 , wherein said peptide is about 10 to about 15 amino acids in length.

12. The composition of claim 1 or 2 , wherein said peptide has an affinity for fibrin.

13. The composition of claim 12 , wherein said peptide comprises one or more non-natural amino acids.

14. The composition of claim 13 , wherein said peptide is selected from:

(SEQ ID NO: 14)

W-dE-C-P(4-OH)-Y(3-Cl)-G-L-C-W-I-Q;

(SEQ ID NO: 15)

Y-dE-C-P(4-OH)-Y(3-Cl)-G-L-C-Y-I-Q;

(SEQ ID NO: 16)

Y-dE-C-P(4-OH)-Y(3-Cl)-G-L-C-W-I-Q;

(SEQ ID NO: 17)

W-dE-C-P(4-OH)-Y(3-Cl)-G-L-C-Y-I-Q;

(SEQ ID NO: 18)

W-dE-C-P(4-OH)-Y(3-Cl)-D-L-C-W-I-Q;

(SEQ ID NO: 19)

Y-dE-C-P(4-OH)-Y(3-Cl)-D-L-C-Y-I-Q;

(SEQ ID NO: 20)

Y-dE-C-P(4-OH)-Y(3-Cl)-D-L-C-W-I-Q;

(SEQ ID NO: 21)

W-dE-C-P(4-OH)-Y(3-Cl)-D-L-C-Y-I-Q;

(SEQ ID NO: 22)

F(4-OMe)-H-C-P(4-OH)-Y(3-Cl)-D-L-C-H-I-L;

(SEQ ID NO: 23)

Y-H-C-P(4-OH)-Y(3-Cl)-G-L-C-W-I-Q;

(SEQ ID NO: 24)

W-dE-C-P-Y(3-Cl)-G-L-C-W-I-Q;

(SEQ ID NO: 25)

W-dE-C-P(4-OH)-Y-G-L-C-W-I-Q;

and

(SEQ ID NO: 26)

F-H-C-P(4-OH)-Y(3-Cl)-D-L-C-H-I-L.

15. The composition of claim 1 or 2 , wherein said peptide has a binding affinity for hyaluronic acid.

16. The composition of claim 15 , wherein said peptide is selected from:

G-A-H-W-Q-F-N-A-L-T-V-R;

(SEQ ID. NO: 1)

T-S-Y-G-R-P-A-L-L-P-A-A;

(SEQ ID. NO: 2)

M-D-H-L-A-P-T-R-F-R-P-A-I;

(SEQ ID. NO: 3)

T-L-R-A-I-W-P-M-W-M-S-S;

(SEQ ID. NO: 4)

I-P-L-T-A-N-Y-Q-G-D-F-T.

(SEQ ID. NO: 5)

17. The composition of claim 1 or 2 , wherein said peptide has an affinity for collagen.

18. The composition of claim 17 , wherein said collagen is a component of myocardium.

19. The composition of claim 17 , wherein said peptide has the following general formula:

X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 ,

(SEQ ID. NO: 8)

wherein:

X 1 is W, C, or A;

X 2 is R, C, or A;

X 3 is E, C, A, K, or T;

X 4 is P, C, or A;

X 5 is D, G, S, C, or A;

X 6 is F, R, C, or A;

X 7 is C, M, or A;

X 8 is A, E, or C;

X 9 is L, M, R, C, or A; and

X 10 is S, N, G, L, C, or A;

wherein, no more than 3 of X 1 -X 10 are C or A, independently; and wherein the total number of C and A residues in X 1 -X 10 is a maximum of 4.

20. The composition of claim 19 , wherein said peptide is selected from:

W-R-E-P-S-F-C-A-L-S;

(SEQ ID. NO: 9)

W-R-E-P-S-F-M-A-L-S;

(SEQ ID. NO: 10)

and

W-R-E-P-G-F-C-A-L-S.

(SEQ ID. NO: 11)

21. The composition of claim 17 , wherein said peptide has the following general formula:

(SEQ ID. NO: 12)

X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 ,

wherein:

X 1 is W, C, or A;

X 2 is R, C, or A;

X 3 is E, C, A, K, or T;

X 4 is P, C, or A;

X 5 is D, G, S, C, or A;

X 6 is F, R, C, or A;

X 7 is C, M, or A;

X 8 is A, E, or C;

X 9 is L, M, R, C, or A;

X 10 is S, N, G, L, C, or A;

X 11 is C, M, or A;

X 12 is P, A, or C; and

X 13 is K, Q, P, H, G, C, or A;

wherein no more than 4 of X 1 -X 13 are C or A, independently; and wherein the total number of C and A residues in X 1 -X 13 is a maximum of 5.

22. The composition of claim 17 , wherein said peptide has the following general formula:

(SEQ ID. NO: 13)

X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -

X 15 ,

wherein:

X 1 is V, I, or C;

X 2 is A, C, R, or D;

X 3 is W, C, or A;

X 4 is R, C, or A;

X 5 is E, C, A, K, or T;

X 6 is P, C, or A;

X 7 is D, G, S, C, or A;

X 8 is F, R, C, or A;

X 9 is C, M, or A;

X 10 is E, A, or C;

X 11 is L, C, A, M, or R;

X 12 is S, C, A, N, G, or L;

X 13 is C, M, or A;

X 14 is P, A, or C; and

X 15 is K, Q, P, H, G, C, or A;

wherein no more than 4 of X 1 -X 15 are C or A, independently; and wherein the total number of C and A residues in X 1 -X 15 is a maximum of 6.

23. The composition of claim 7 , wherein said linker comprises a linear, branched, or cyclic peptide sequence.

24. The composition of claim 23 , wherein said peptide sequence comprises a linear dipeptide.

25. The composition of claim 24 , wherein said linear dipeptide is G-G.

26. The composition of claim 7 , wherein said linker comprises an amide, sulfonamide, urea, thiourea, or carbamate moiety.

27. The composition of claim 26 , wherein said linker is an amide, sulfonamide, urea, thiourea, or carbamate moiety.

28. The composition of claim 7 , wherein said linker comprises a linear, branched, or cyclic alkane, alkene, or alkyne, or a phosphodiester moiety.

29. The composition of claim 28 , wherein said linker is a linear, branched, or cyclic alkane, alkene, or alkyne, or a phosphodiester moiety.

30. The composition of claim 29 , wherein said linker is substituted with one or more the following moieties: ketone, ester, amide, ether, carbonate, sulfonamide, or carbamate.

31. The composition of claim 7 , wherein said linker is selected from:

—NH—CO—NH—; —

—CO—(CH 2 ) n —NH—;

dpr;

dab;

—NH-Ph-;

—NH—(CH 2 ) n —;

—CO—NH—;

—(CH 2 ) n —NH—;

and

—CS—NH—;

wherein n is 1 to 10.

32. A composition comprising a contrast agent, or a pharmaceutically acceptable salt thereof, having a structure:

wherein said composition has an enantiomeric excess of greater than 85% of the (R) isomer at the 2 position of the metal chelate.

33. The composition of claim 32 , wherein said composition has an enantiomeric excess of about 97% or more of the (R) isomer at the 2 position of the metal chelate.