Porphyrins texaphyrins

Sessler, J. L. Allen, W. E. Krai, V. A. Preparation of highly boronated derivatives of expanded porphyrins (texaphyrins) for potential use in boron neutron capture therapy and related applications. US Patent 5,955,586, 1999 Chem. Abstr. 1999, 131, 222611. 

Texaphyrins (i.e. metal-coordinating expanded porphyrins, Fig. 27) have recently been investigated as new drugs for applications in radioimaging and PDT (140). 

Metal porphyrins as well as texaphyrin and phthalocyanin complexes are also featuring in the development of new photodynamic and sonodynamic therapeutic modes. 

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... 

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],... 

Sessler, J.L. et al. (1996) New texaphyrin-type expanded porphyrins, Pure Appl. Chem. 68, 1291-1295. 

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. 

Figure 17.5 Skeleton structures of (a) polypyrrolic photosensitizers (i) porphyrin, (ii) chlorine, (Hi) bacteriochlorin, (iv) phthalocyanine, (v) naphthalocyanine, (vi) texaphyrin (b) examples of metalloderivatives (c) photosensitizers incorporating the metallodrug moieties (x-xii) cisplatin- and/or carboplatin-like structures, (xiii) iron sulphur nilrosy cluster...

Texaphyrin, (II), (4), has a central core that is 20% larger than porphyrin. It has been prepared to encapsulate cations considerably larger than porphyrin containable counterpart. 

A new type of complex with a different spectroscopic application is provided by the texaphyrins, compounds of extended porphyrins where the ring contains five donor nitrogens. These have attracted considerable interest because of their possible medicinal applications. 

The final in vitro photodynamic studies involved the use of human cancer cells. Here, K562 leukemic cells of myelocutic origin were used. The texaphyrin complex 116 was very effective in the photo-eradication of K562 leukemic cells, being considerably more effective than hematoporphyrin under similar conditions. This suggests that the texaphyrin expanded porphyrins, as a class of photosensitizers, could have further application in the photo-kilUng of these and other cancer cells... 

With the exception of the texaphyrins of Sessler et al. [59, 60, 65, 95] vide supra) the sapphyrin macrocycle and its heteroatom analogues (c.f. Scheme 36) are perhaps the best studied of the expanded porphyrins prepared to date. Sapphyrin was the first example of an expanded porphyrin to be reported, being discovered... 

The use of porphyrins and porphyrin-like macrocycles, namely the texaphyrins, which show good selectivity towards tumor cells, could be used to overcome the limitations of the current sensitizers, namely a lack of suitable biolocalization and a consequent high toxicity at the needed therapeutic doses [25]. The strengths and weaknesses of this approach are detailed below. 

There are two critical features of the texaphyrins that led to the consideration that it could function as a radiation sensitizer. First, this class of molecules, like the porphyrins, is known to localize with high selectivity in cancerous tissues. Second, the texaphyrins are known to contain a low-lying LUMO in comparison to porphyrins and most other endogenous species, they are thus very easy to reduce... 

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