Six-coordinate Iron(II) and Cobalt(II) paraSHIFT Agents for Measuring Temperature by Magnetic Resonance Spectroscopy

Abstract

Paramagnetic Fe(II) and Co(II) complexes are utilized as the first transition metal examples of 1H NMR shift agents (paraSHIFT) for thermometry applications using Magnetic Resonance Spectroscopy (MRS). The coordinating ligands consist of TACN (1,4,7-triazacyclononane) and CYCLEN (1,4,7,10-tetraazacyclododecane) azamacrocycles appended with 6-methyl-2-picolyl groups, denoted as MPT and TMPC, respectively. 1H NMR spectra of the MPT- and TMPC-based Fe(II) and Co(II) complexes demonstrate narrow and highly shifted resonances that are dispersed as broadly as 440 ppm. The six-coordinate complex cations, [M(MPT)]2+ and [M(TMPC)]2+, vary from distorted octahedral to distorted trigonal prismatic geometries, respectively, and also demonstrate that 6-methyl-2-picolyl pendents control the rigidity of these complexes. Analyses of the 1H NMR chemical shifts, integrated intensities, line widths, the distances obtained from X-ray diffraction measurements and longitudinal relaxation time (T1) values allow for the partial assignment of proton resonances of the [M(MPT)]2+ complexes. Nine and six equivalent methyl protons of [M(MPT)]2+ and [M(TMPC)]2+, respectively, produce three-fold higher 1H NMR intensities compared to other paramagnetically shifted proton resonances. Among all four complexes, the methyl proton resonances of [Fe(TMPC)]2+ and [Co(TMPC)]2+ at −49.3 ppm and −113.7 ppm (37 °C) demonstrate the greatest temperature dependent coefficients (CT) of 0.23 ppm/°C and 0.52 ppm/°C, respectively. The methyl groups of these two complexes both produce normalized values of |CT|/FWHM = 0.30 °C−1, where FWHM is full width at half maximum (Hz) of proton resonances. The T1 values of the highly shifted methyl protons are in the range of 0.37–2.4 ms, allowing rapid acquisition of spectroscopic data. These complexes are kinetically inert over a wide range of pH values (5.6–8.6), as well as in the presence of serum albumin and biologically relevant cations and anions. The combination of large hyperfine shifts, large temperature sensitivity, increased signal-to-noise ratio and short T1 values suggests that these complexes, in particular the TMPC-based complexes, show promise as paraSHIFT agents for thermometry.

Gear Up for a pH Shift: A Responsive Iron(II) 2-Amino-6-picolyl-Appended Macrocyclic paraCEST Agent That Protonates at a Pendent Group

“…TMPC produces six-coordinate, rigid and redox-stable Fe(II) and Co(II) complexes, which are shown in Scheme 1. 40 These paramagnetic complexes demonstrate hyperfine shifted proton resonances of the ligand and an effective magnetic moment (μ eff ) of 5.7 ± 0.1 and 6.0 ± 0.3 BM in aqueous solution, which is indicative of high spin Fe(II) and Co(II) ions, respectively. The methyl substituents flanking the pyridine N -donor groups in these Fe(II) and Co(II) ions give highly shifted 1 H NMR resonances at −49.3 and −113.7 ppm, respectively, at 37 °C.…”

“…As we have recently shown, the parent [Fe(TMPC)] 2+ complex has six-coordinate C 2 -symmetrical geometry present in a single diastereomeric form. 40 Based on comparison of the solution properties of the two complexes together with the solid state structure of [Fe(TMPC)] 2+ , we propose that [Fe(TAPC)] 2+ also adopts six-coordinate C 2 -symmetrical geometry. In this geometry, the Fe(II) ion is coordinated to all four nitrogen donors of CYCLEN macrocycle and two picolyl nitrogen donors.…”

“…43 The TAPC complexes were readily formed in methanol-water (1:1) solutions according to a previously reported procedure. 40 The detailed synthetic protocols are described in the Experimental Section.…”

“…40 In a typical procedure, TAPC (0.1 mmol) was dissolved in a mixture of acetonitrile (0.4 mL) and water (0.8 mL) at pH below 4.0 followed by addition of 1 equiv. of Fe(II) or Co(II) salt.…”

Holmium Сomplex with DOTA as NMR Super-Sensitive Temperature Sensor Reagent for Spectroscopic and Tomography Monitoring of Aqueous Systems

“…[1,3,[5][6] Необходимо отметить, что параллельно с развитием методов анализа парамагнитных комплексов Ln также развивались взаимодополняющие методические под-ходы к изучению парамагнитных нитроксильных ради-калов и комплексов d-элементов. [10][11][12][13] Ранее нами в ряде экспериментальных исследований проводился анализ молекулярной динамики и особенностей парамагнитных свойств комплексов Ln в органических растворах.…”