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

Fe^II, Co^II and Ni^II complexes of two tetraazamacrocycles (1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane (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^II, Co^II and Ni^II complexes of L1 show up to four CEST peaks shifted ≤112ppm, whereas analogous complexes of L2 show only a single CEST peak at ≤69ppm. Comparison of the temperature coefficients (C_T) of the CEST peaks of [Co(L2)]²⁺, [Fe(L2)]²⁺, [Ni(L1)]²⁺ and [Co(L1)]²⁺ showed that a CEST peak of [Co(L1)]²⁺ gave the largest C_T (-0.66ppm ^oC^-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)]²⁺ and [Co(L1)]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)]²⁺ complex has an unusual eight-coordinate Fe^II bound to four amide oxygen atoms and four macrocyclic nitrogen atoms. For [Co(L2)]²⁺, one structure has seven-coordinate Co^II with three bound amide pendents and a second structure has a six-coordinate Co^II with two bound amide pendents.