Texaphyrins and

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

Synthesis and characterization of other related macrocycles, including chlorins, " isobacteriochlorins, bacteriochlorins, mono- and dioxoporphyrins, " other more highly saturated hydroporphyrins, N-alkyl- or A-arylporphyrins, some of which are chiral, porphodimethenes, thiaporphyrins, " oxaporphyrins, N-confused " and carbapor-phyrins, porphycenes " and corrphycenes, " tetraazaporphyrins, phthalocyanines, the ring-expanded sapphyrins, texaphyrins and others, and the ring-contracted corroles " and corrolazines have also been synthesized and are discussed in the indicated references. 

Complexes of Porphyrins, Phthalocymines, Aza Macrocycles, Texaphyrins, and Related Ligands... 

Figure 9.1.6 Structure of Texaphyrin and the Lone-star Pentagonal Binding Geometry Provided by its Pentaaza Core...

The metallotexaphyrins have also been found to be easy to reduce and capable of capturing hydrated electrons in aqueous solution. This has made them of potential interest as X-ray radiation therapy (XRT) enhancement agents. While a discussion of this and other applications of metallotexaphyrins is deferred to Chapter 10 of this book, it is worth mentioning that preliminary results have been obtained that are highly encouraging. This, in turn, is stimulating on-going efforts to prepare additional texaphyrin and texaphyrin-like macrocycles. ... 

G. Kostenich, A. Orenstein, L. Roitman, Z. Malik, B. Ehrenberg (1997). In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system. J. Photochem. PhotobioL B, 39, 36-42. 

In spite of the heavy atom, compound (32) is sufficiently fluorescent for this to be used as an analytical tool to examine localization and pharmacokinetics. In EMT-6 murine tumors, (32) localizes initially on lysosomes, with selectivity for tumor over surrounding normal tissue, and with evidence for apoptotic cell kill.137 Fluorescence studies using a hamster cheek pouch model show a maximum emission in 2-3 h, with selectivity for the tumor (x 1.5 over normal tissue) after 24 h the photosensitizer is no longer detectable.138 Lutetium texaphyrin (32) has been compared... 

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. 

Figure 1.17 The texaphyrin-gadolinium chelate structure used as a photosensitizer and MRI contrast agent in the detection and treatment of cancer.

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

Metal-texaphyrin complexes such as 55 selectively accumulate in tumor cells (240) (see Section III). Complex 55 readily undergoes aone-electron reduction (Ei/2 = 0.08 V vs NHE), forming a free radical which is capable of damaging DNA. Because of the high electron affinity of 55, it may prolong the lifetime of HO- radicals formed by radiolysis of water. Complex 55 is now in phase II clinical trials for the treatment of brain tumors and lung, head, neck, and pancreatic cancer. 

Metal-texaphyrin complexes are readily taken up by tumor cells and have clinical potential as photosensitizers (see Section III) and... 

In the presence of anions such as phosphate and oxalate, the relaxivity of [Gd(Tex)]2+ is considerably reduced revealing that these anions compete with water for binding to the Gd3+ ion [167,171]. Most likely, texaphyrin complexes self-associate due to strong van der Waals interactions. UV-VIS studies suggest that the aggregates dissociate upon interaction with polyuronides (pectate, alginate), which probably act as polydentate polycarboxylate ligands for the [Gd(Tex)]2+ complexes [173]. 

Sessler, J.L. and Miller, R.A. (2000) Texaphyrins new drugs with diverse clinical applications in radiation and photodynamic therapy, Biochem. Pharmacol. 59, 733-739. 

TEXAPHYRIN CONJUGATES. PROGRESS TOWARDS SECOND GENERATION DIAGNOSTIC AND THERAPEUTIC AGENTS... 

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],... 

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