title: The reactivity of macrocyclic Fe(II) paraCEST MRI contrast agents towards biologically relevant anions, cations, oxygen or peroxide.
abstract: The reactivity of four macrocyclic Fe(II) complexes (L1-L4) is studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) magnetic resonance imaging (MRI) contrast agents for in vivo studies. (L1 = 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane; L2 = 1,4,7-tris[(5-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane; L3 = 1,4,7-tris[(2-pyridyl)methyl]-1,4,7-triazacyclononane; L4 = 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). The Fe(II) complexes remain intact in the presence of 25 mM carbonate, 0.40 mM phosphate and 100mM NaCl for 12h at 37 °C, consistent with their moderately high formation constants (log K=13.5, 19.2, 7.50 for [Fe(L1)](2+), [Fe(L3)](2+) and [Fe(L4)](2+), respectively). [Fe(L4)](2+), [Fe(L2)](2+) and [Fe(L3)](2+) do not dissociate over 12h in the presence of excess Cu(II) at 37 °C. None of the complexes show appreciable redox cycling as measured by consumption of ascorbate in the presence of oxygen, corresponding to their highly stabilized Fe(II) oxidation state (E(o)=860, 930, 970, and 800 mV versus NHE for [Fe(L1)](2+), [ [Fe(L2)](2+), [Fe(L3)](2+) and [Fe(L4)](2+). None of the Fe(II) complexes produce appreciable amounts of hydroxyl radical in the presence of peroxide and ascorbate as shown by limited hydroxylation of benzoate. Fe(II) complexes of L1, L2, and L3 show 25-28% cleavage of supercoiled plasmid DNA in the presence of peroxide and ascorbate over 2h at 37 °C while [Fe(L4)](2+) shows 6% cleavage.
authors: Department of Chemistry, University at Buffalo, State University of New York, Amherst, NY 14260, United States.
authors: Sarina J
authors: SJ
authors: Dorazio
authors: Pavel B
authors: PB
authors: Tsitovich
authors: Stephanie A
authors: SA
authors: Gardina
authors: Janet R
authors: JR
authors: Morrow
mesh_terms: D000838:Anions; D001205:Ascorbic Acid / Q000737:chemistry; D001565:Benzoates / Q000737:chemistry; D002412:Cations; D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D053837:DNA Cleavage; D005296:Ferrous Compounds / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006900:Hydroxylation; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D019047:Phantoms, Imaging; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D000838:Anions; D001565:Benzoates; D002412:Cations; D003287:Contrast Media; D056831:Coordination Complexes; D005296:Ferrous Compounds; D008024:Ligands; D047028:Macrocyclic Compounds; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D010100:Oxygen