Compounds for use as iron (III) MRI contrast agents containing anionic pendents and ancillary groups
Macrocyclic complexes and macrocyclic compounds. The macrocyclic complexes or macrocyclic compounds have a TACN moiety with one or more amine group(s) or a O- or S-substituted TACN moiety. The macrocyclic complexes have a high-spin Fe(III) atom coordinated to the TACN moiety. The macrocyclic complexes can be used in imaging methods.
1. A macrocyclic complex comprising:
a 1,4,7-triazacyclononane (TACN) moiety or an O-substituted TACN moiety having a structure:
wherein R 1 , Z 1 , Z 2 , and Z 3 are anionic pendent groups independently chosen from:
deprotonated analogs thereof, and combinations thereof,
wherein R 3 is a substituted or unsubstituted alkyl or a substituted or unsubstituted aryl group and R 4 is a substituted alkyl or unsubstituted alkyl or a substituted or unsubstituted aryl group; and
a high-spin Fe(III) cation complexed to the TACN moiety and at least one anionic pendent group substituent of the TACN moiety, or a high-spin Fe(III) cation complexed to the O-substituted TACN moiety and at least one anionic pendent group substituent of the O-substituted TACN moiety,
wherein:
when the macrocyclic complex is:
Z 1 and Z 2 are
and Z 3 is not
and
when the macrocyclic complex is:
Z 1 and Z 2 are
wherein R 4 is an unsubstituted aryl, and Z 3 is not
wherein R 4 is an unsubstituted aryl.
2. The macrocyclic complex of claim 1 , wherein at least one or all of the one or more pendent groups is covalently bound to a nitrogen atom on the TACN moiety or an O-substituted TACN moiety.
3. The macrocyclic complex of claim 1 , wherein the macrocyclic complex has at least one open coordination site.
4. The macrocyclic complex of claim 1 , wherein the macrocyclic complex has at least one water complexed to the high-spin Fe(III) cation.
5. A macrocyclic complex comprising:
a 1,4,7-triazacyclononane (TACN) moiety having a structure:
wherein Z 1 and Z 2 are anionic pendent groups independently chosen from:
deprotonated analogs thereof, and combinations thereof,
R 1 is an anionic pendent groups independently chosen from:
deprotonated analogs thereof, and combinations thereof,
wherein R 2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aromatic group or a substituted ether; R 3 is a substituted or unsubstituted alkyl or a substituted or unsubstituted aryl group; R 4 is a substituted alkyl or unsubstituted alkyl or a substituted or unsubstituted aryl group; and Q 1 is aryl substituted with an anionic group, an alkyl group substituted with an anionic group or an aralkyl group substituted with an anionic group; and
a high-spin Fe(III) cation complexed to the TACN moiety and at least one anionic pendent group substituent of the TACN moiety.
6. The macrocyclic complex of claim 5 , wherein at least one or all of the one or more pendent groups is covalently bound to a nitrogen atom on the TACN moiety.
7. The macrocyclic complex of claim 5 , wherein the macrocyclic complex has at least one open coordination site.
8. The macrocyclic complex of claim 5 , wherein the macrocyclic complex has at least one water and/or at least one hydroxide complexed to the high-spin Fe(III) cation.