| Autor: |
Kras EA; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260, USA. jmorrow@buffalo.edu., Cineus R; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260, USA. jmorrow@buffalo.edu., Crawley MR; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260, USA. jmorrow@buffalo.edu., Morrow JR; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260, USA. jmorrow@buffalo.edu. |
| Abstrakt: |
High-spin Fe(III) complexes of 1,4,7-triazacyclononane (TACN) with mixed oxygen donor pendants including hydroxypropyl, phenolate or amide groups are prepared for study as T 1 MRI probes. Complexes with two hydroxypropyl pendants and either amide (Fe(TOAB)) or phenolate (Fe(PTOB)) groups are compared to an analog with three hydroxypropyl groups (Fe(NOHP)), in order to study the effect of the third pendant on the coordination sphere as probed by solution chemistry, relaxivity and structural studies. Solution studies show that Fe(PTOB) has two ionizations with the phenol pendant deprotonating with a p K a of 1.7 and a hydroxypropyl pendent with p K a of 6.3. The X-ray crystal structure of [Fe(PTOB)]Br 2 features a six-coordinate complex with two bound hydroxypropyl groups, and a phenolate in a distorted octahedral geometry. The Fe(TOAB) complex has a single deprotonation, assigned to a hydroxypropyl group with a p K a value of 7.0. Both complexes are stabilized as high-spin Fe(III) in solution as shown by their effective magnetic moments and Fe(III)/Fe(II) redox potentials of -390 mV and -780 mV versus NHE at pH 7 and 25 °C for Fe(TOAB) and Fe(PTOB) respectively. Both Fe(PTOB) and Fe(TOAB) are kinetically inert to dissociation under a variety of challenges including phosphate/carbonate buffer, one equivalent of ZnCl 2 , two equivalents of transferrin or 100 mM HCl, or at basic pH values over 24 h at 37 °C. The r 1 relaxivity of Fe(TOAB) at 1.4 T, pH 7.4 and 33 °C is relatively low at 0.6 mM -1 s -1 whereas the r 1 relaxivity of Fe(PTOB) is more substantial and shows an increase of 2.5 fold to 2.5 mM -1 s -1 at acidic pH. The increase in relaxivity at acidic pH is attributed to protonation of the phenolate group to provide an additional pathway for proton relaxation. |
