Compounds for use as iron(III) MRI contrast agents

A macrocyclic complex comprising:

• a macrocyclic core, wherein the macrocyclic core is a TACN group, an S-substituted TACN, an O-substituted TACN, or a cyclam group having the following structure:
• and Z1, Z2, Z3, and Z4 are each independently H or one or more of the following pendant groups:
• or a deprotonated analog thereof or a stereoisomer thereof, wherein R is methyl, R1, R2, and R3 are each independently a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted alkyl group, and R1, R2, and R3 are not pendant donors;
• Q1 and Q2 are each independently H, OCH3, CO2H, or CH2CO2G4, G4 is H, C1 to C12 substituted or unsubstituted alkyl groups of linear or branched structure or a (—CH2CH2O—)n group, wherein n is 1-2, Q3 is H, C1 to C12 substituted or unsubstituted alkyl groups of linear or branched structure or a (—CH2CH2O—)n group, wherein n is 1-12, Q4 and Q5 are each independently H, OCH3, CO2H, or substituted or unsubstituted alkyl groups of linear or branched structures, A is a substituted or unsubstituted alkyl group of linear or branched structure with C1 to C12 or is a substituted or unsubstituted aryl group or an amino acid, and
• a high-spin Fe(III) cation complexed to the macrocyclic core and at least one pendant group, or a salt, a partial salt, a hydrate, a polymorph, or a stereoisomer thereof,
• wherein the macrocyclic complex exhibits a redox potential of less than 0 vs. normal hydrogen electrode (NHE) in an aqueous medium at a pH of 6.5-7.5,
• wherein the macrocyclic core has structure I, Z1 is H and Z2 and Z3 are each independently a pendant group;
• wherein the macrocyclic core has structure II, III, or XV, Z1 and Z2 are each independently a pendant group;
• wherein the macrocyclic core has structure XVI, Z1 is a pendant group;
• wherein the macrocyclic core has structure XII, Z4 is a pendant group and Z1, Z2 and Z3 are each independently H or a pendant group, provided that at most two of Z1, Z2, and Z3 are H;
• wherein the macrocyclic core has structure XIII, Z1 and Z3 are each independently a pendant group and Z2 is H or a pendant group;
• wherein for all structures I, II, III, XII, XIII, XIV, XV, and XVI, each of Z1, Z2, Z3 and Z4, as applicable, are selected independently of each other.