Six, Seven or Eight Coordinate Fe super(II), Co super(II) or Ni super(II) Complexes of Amide-Appended Tetraazamacrocycles for ParaCEST Thermometry

• Published in: Chemistry : a European journal 2015-12, Vol.21 (50), p.18290-18300
• Main Authors: Olatunde, Abiola O, Bond, Christopher J, Dorazio, Sarina J, Cox, Jordan M, Benedict, Jason B, Daddario, Michael D, Spernyak, Joseph A, Morrow, Janet R
• Format: Article
• Language: English
• Subjects: Amides; Coordination compounds; Exchange; Magnetic resonance imaging; Nitrogen atoms; Oxygen atoms; Saturation; Spectra
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201503125

Fe super(II), Co super(II) and Ni super(II) complexes of two tetraazamacrocycles (1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradec a ne (L1) and 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (L2) show promise as paraCEST agents for registration of temperature (paraCEST=paramagnetic chemical exchange saturation transfer). The Fe super(II), Co super(II) and Ni super(II) complexes of L1 show up to four CEST peaks shifted less than or equal to 112ppm, whereas analogous complexes of L2 show only a single CEST peak at less than or equal to 69ppm. Comparison of the temperature coefficients (C sub(T)) of the CEST peaks of [Co(L2)] super(2+), [Fe(L2)] super(2+), [Ni(L1)] super(2+) and [Co(L1)] super(2+) showed that a CEST peak of [Co(L1)] super(2+) gave the largest C sub(T) (-0.66ppm super(o)C super(-1 ) at 4.7T). NMR spectral and CEST properties of these complexes correspond to coordination complex symmetry as shown by structural data. The [Ni(L1)] super(2+) and [Co(L1)] super(2+) complexes have a six-coordinate metal ion bound to the 1-, 4-amide oxygen atoms and four nitrogen atoms of the tetraazamacrocycle. The [Fe(L2)] super(2+) complex has an unusual eight-coordinate Fe super(II) bound to four amide oxygen atoms and four macrocyclic nitrogen atoms. For [Co(L2)] super(2+), one structure has seven-coordinate Co super(II) with three bound amide pendents and a second structure has a six-coordinate Co super(II) with two bound amide pendents. Changes in coordination affect MRI contrast: The remarkably different chemical exchange saturation transfer (CEST) spectra of Co super(II), Fe super(II) or Ni super(II) complexes of amide-appended macrocycles is based on the different coordination geometries for complexes of the two ligands. The complexes with the most highly shifted CEST peaks show promise for the development as magnetic resonance imaging (MRI) temperature probes for thermometry.