title: Imidazole-Appended Macrocyclic Complexes of Fe(II), Co(II), and Ni(II) as ParaCEST Agents.
abstract: The solution chemistry and solid state structures of the Co(II), Fe(II), and Ni(II) complexes of N,N'-bis(imidazole-2-ylmethyl)-4,10-diaza-15-crown-5 (HINO) are reported. The Co(II) and Ni(II) complexes of HINO are the first examples of paraCEST agents (paramagnetic chemical exchange saturation transfer) that feature exchangeable imidazole NH protons. The crystal structures of [Co(HINO)]CoCl4·H2O and [Fe(HINO)](CF3SO3)2have the metal ions coordinated to four nitrogen and three oxygen donor atoms of the macrocyclic ligand in a distorted pentagonal bipyramidal geometry. In [Ni(HINO)](CF3SO3)2, the nickel ion is bound to only two of the three ether oxygens and three nitrogens to produce a complex with a distorted octahedral geometry. The1H NMR spectra of the three paramagnetic complexes show resonances characteristic of effective C2symmetry in solution. CEST peaks attributed to the imidazole NH proton of the pendent group are observed at 32 and 55 ppm away from bulk water for [Co(HINO)]2+and [Ni(HINO)]2+, respectively, on a 11.7 or 9.4 T NMR spectrometer. For both complexes, an optimal CEST effect was observed at pH 7.2, and the rate constant for proton exchange under these conditions was 1.0 × 103s-1. [Fe(HINO)]2+did not produce a CEST peak due to oxidation of the complex in water at neutral pH. The CEST peak of [Co(HINO)]2+or [Ni(HINO)]2+is observed in the presence of human serum albumin (HSA). These complexes show enhanced kinetic inertness toward dissociation in acid or in the presence of HSA in comparison to analogous complexes with amide pendent groups.
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York , Amherst, New York 14260, United States.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Burns
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York , Amherst, New York 14260, United States.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Cox
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York , Amherst, New York 14260, United States.
authors.forename: Janet R
authors.identifier: http://orcid.org/0000-0003-4160-7688
authors.initials: JR
authors.lastname: Morrow