Gadolinium-texaphyrin complexes

Figure 3 Single crystal X-ray diffraction structure of the gadolinium texaphyrin complex PCI-0101 (2) (bis-nitrate form) showing the planar nature of the basic monoanionic texaphyrin macrocycle and the four putative inner sphere coordination sites for water (occupied by two apical methanol molecules and a bidentate nitrate anion in this structure). The Gd(III) ion is nine-coordinate and lies 0.60 A out of the plane through the five nitrogen atoms of the macrocycle. Most hydrogen atoms have been omitted for clarity. Thermal ellipsoids have been scaled to the 30% probability level. Reproduced from [22] with permission. 1993 American Chemical Society...

Another approach has been tackled with by Sessler et al. [37, 38] who described gadolinium(III) complexes with texaphyrins as potential MRI contrast agents. When the expanded porphyrin ring is subtituted by water solubilizing groups (Fig. 5), the chelate is sufficiently water soluble to be injected. It is... 

Young, S.W. et al. (1994) Preclinical evaluation of gadolinium(III) texaphyrin complex. A new paramagnetic contrast agent for magnetic resonance imaging, Invest Radiol. 29, 330-338. 

Geraldes, C.F. et al. (1995) Nuclear magnetic relaxation dispersion studies of water-soluble gadolinium(III)-texaphyrin complexes, J. Magn. Reson. Imag. 5, 725-729. 

The formation of a number of lanthanide texaphyrin complexes has been reported [95]. In all cases, metal insertion and oxidation proceeds smoothly (Scheme 16) [95]. The complexes demonstrate fair water solubility and good stability towards hydrolysis. Detailed kinetic studies of complex 147, for instance indicated that the half-life for decomplexation and/or decomposition of this complex is 37 days in a 1 1 mixture of MeOH H20 (pH7). Thus, it appears that gadolinium (III) complexes of texaphyrins could provide the basis for a new approach to paramagnetic MRI contrast reagent development [95]. 

As shown in Fig. 7.6, texaphyrins have a larger cavity than porphyrins so they can form complexes with lanthanide metals such as gadolinium (XCYTRIN ), that enhances the efficacy of treatment for certain brain tumours, and lutetium (LUTRIN ), used as a sensitizer for photodynamic therapy of recurrent breast cancer [17], Crucial to their success is the increased number of donor atoms available as the more lanthanide binding sites that a ligand can satisfy, the more stable the complex. 

Metallotexaphyrins are typically rather soluble in polar media. In fact, complexes such as the all-alkyl systems 9.70-9.72 show significant solubility (to ca. 10 M concentrations) in 1 1 (v/v) methanol/water mixtures. Perhaps more importantly, metallotexaphyrins have been demonstrated to be rather hydrolytically inert. For instance, detailed kinetic studies carried out on a solution of gadolinium(III) texaphyrin 9.70 in a 1 1 methanol/water mixture revealed that the half-life for... 

Two texaphyrin (aromatic pentadentate ligands) complexes, motexafin gadolinium and lutetium, were extracted fixim plasma and separated on a SS°C C g column (A = 470 nm) using a 59/21/20 water (0.1 M ammonium acetate to pH 4.3 with acetic acid)/acetonitrile/methanol mobile phase. Peaks were well resolved and elution was complete in 20min. Linear ranges from 0.01-30pM and quantitation limits of 0.01 pM gadolinium and 0.1 pM lutetium were reported [925]. 

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