Texaphyrins, lanthanide

As proved true for NADPH, addition of a catalytic amount of MGd to aerated solutions of ascorbate led to rapid, catalytic oxidation and concurrent production of hydrogen peroxide in accord with Eqn. 3, Scheme 1. However, in contrast to what was observed with NADPH, in the case of ascorbate, MGd was found to be a substantially more effective oxidation catalyst than MLu or two other lanthanide(III) texaphyrin complexes containing smaller coordinated cations, namely Dy-Tex (4) and Er-Tex (5). Other lanthanide(III) texaphyrins containing larger cations, namely the Eu(III), Sm(III), and Nd(III) complexes (6-8, respectively) showed rates that were similar to those of MGd. Initial rates of reaction therefore appear to fall into two groups, that correlate with ionic radius, as can be seen for the seven texaphyrin lanthanide congeners shown in Figure 5. 

Although structurally and spectrally similar, the differing redox and photophysical properties of the various lanthanide(III) texaphyrin complexes allow their use in such disparate areas as PDT, direct cancer treatment, and both X-ray and chemotherapy enhancement protocols. Both compounds 1 and 2 generate reactive oxygen species (ROS), albeit via mechanistically distinct pathways (vide infra). The ROS are thought to be responsible, at least in part, for the observed biological activity of MGd and MLu [22],... 

The cadmium(II) complex corresponding to 9 (M = Cd n = 2) was the first texaphyrin made [6], This aromatic expanded porphyrin was found to differ substantially from various porphyrin complexes and it was noted that its spectral and photophysical properties were such that it might prove useful as a PDT agent. However, it was also appreciated that the poor aqueous solubility and inherent toxicity of this particular metal complex would likely preclude its use in vivo [29-31], Nonetheless, the coordination chemistry of texaphyrins such as 9 was soon generalized to allow for the coordination of late first row transition metal (Mn(II), Co(II), Ni(II), Zn (II), Fe(III)) and trivalent lanthanide cations [26], This, in turn, opened up several possibilities for rational drag development. For instance, the Mn(II) texaphyrin complex was found to act as a peroxynitrite decomposition catalyst [32] and is being studied currently for possible use in treating amyotrophic lateral sclerosis. This work, which is outside the scope of this review, has recently been summarized by Crow [33],... 

The structurally similar, but magnetically distinct, lanthanide(III) texaphyrin complexes, MLu and MGd both generate reactive oxygen species (ROS), albeit via different mechanisms. Photoirradiation of MLu causes excitation from the singlet ground state to the triplet state (Fig. 3). 

Sessler, J.L. et al. (1997) Biomedical applications of lanthanide(III) texaphyrins. Lutetium(III) texaphyrins as potential photodynamic therapy photosensitizers, J. Alloys Compd. 249, 146-152. 

Fig. 4. Structure and reference frame for the dimethoxy tetraethyl dimethyl trivalent lanthanide texaphyrin. The a angle measures the out-ofplane location of / (Ill) with respect to the mean macrocyclic plane (adapted from Lisowski et al. (1995a)).

Invariably hydrolytic instability of lanthanide Por complexes, particularly that observed for the larger lanthanide elements, negatively influences their prospective application in terms of biomedicine (Sect. 7.4). As a response to this problem, larger porphyrin-like or expanded porphyrins , the so-called texaphyrins (Tx), have been examined by Sessler et al. [246]. The motivation, that expanded systems better accommodate larger ions, was previously demonstrated in a uranyl superphthalocyanine (SPc) complex [247], This SPc-complex contains an expanded, cyclic five-subunit pentakis(2-iminoisoindoline) which is formed by a template reaction of o-dicyanobenzene with anhydrous uranyl chloride. The uranium is displaced by only 0.02 A from the mean N5-plane. 

The central hole or binding core in texaphyrins is roughly 20% larger than that of the porphyrins and accomplishes pentadentate binding [247]. In the course of the studies to exploit coordination behavior with lanthanide cations a serious of monoanionic texaphyrine complexes have been synthesized and fully characterized (Eq. 17, Table 20) [248],... 

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. 

Sessler JL et al (1993) Synthesis and structural characterization of lanthanide(III) texaphyrins. Inorg Chem 32 3175-3187... 

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]. 

Although quite new on the scientific scene, the lanthanide complexes of the texaphyrins are considered to be of particular interest. This derives in larger measure from their documented stability in aqueous solution and the relative ease with which the basic core structure can be subjected to variations in substituents and functionality. With the increasing use of lanthanide-based shift reagents in medical diagnosis, the continued study of these new systems could prove to be of considerable interest... 

A review of expanded porphyrin hgands can be fonnd. The texaphyrins (8) can be considered as 22-tt-electron benzaimnlene systems with an IS-tt-electron delocahzation path, based on crystal stmctnre data as well as NMR. The cadminm complex of the macrocycle is fonnd to be planar with pentadentate coordination of the macrocycle to cadminm, which becomes seven-coordinate as a resnlt of axial coordination to two pyridine molecnles. The cavity is nearly circular with a center-to-nitrogen distance of 2.39 A. Because of the larger size of this macrocycle, metal ion coordination is generally seen with the larger transition metals and lanthanides. 

As alluded to above, metal complexes of a number of lanthanide and actinide texaphyrin complexes have also been prepared. In the case of Dy(III) texaphyrin 9.74, as in the case of the bis-pyridine cadmium complex 9.61b, the metal center sits directly within the mean plane of the macrocycle (Figure 9.1.12). This result stands in direct contrast to the highly labile, typically sandwich-type 2 1 or 3 2 complexes observed for porphyrin complexes with these larger metal cations. ... 

Figure 10.4.4 Schematic Representation of the Lanthanide(IIl) Texaphyrin-based Approach to Antisense-type RNA Hydrolysis...

Basic Metal Binding Chemistry of the Texaphyrins. There are several salient features that define the texaphyrins. Of these, perhaps the most remarkable is their ability to act as pentadentate ligands. Indeed, in contrast to other expanded porphyrins, this class of expanded porphyrins is able to form stable, non-Iabile complexes with a range of large cations including Cd +, Hg +, In +, La +, and all members of the lanthanide series (except radioactive Pm + which has not... 

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