One-Electron Reduction and Oxidation Studies of the Radiation Sensitizer Gadolinium(III) Texaphyrin (PCI-0120) and Other Water Soluble Metallotexaphyrins

Abstract

The radiation sensitizer gadolinium(III) texaphyrin 2 (XYTRIN; PCI-0120; Gd−Tex2+) and several other water soluble metallotexaphyrin complexes were prepared and studied using pulse radiolysis. All of the metallotexaphyrins were found to react with solvated electrons and hydroxyl radicals, yielding the corresponding one-electron reduced and oxidized metallotexaphyrins, respectively. The rates of the reduction processes range from 3.7 × 1010 to 6.8 × 1010 M-1 s-1 (±10%), while those involving oxidation range from 2.5 × 109 to 7.4 × 109 M-1 s-1 (±10%). The spectral characteristics of the transformed metallotexaphyrins produced by these reactions, e.g., a broad absorption band with a λmax centered around 830 nm, are consistent with ligand-centered redox processes. Reaction of the metallotexaphyrins with solvated electrons affords species which exhibit metal dependent behavior. In the absence of hydroxyl radicals, the decay of the reduced metallotexaphyrins produced by reaction with electrons involves an initial protonation event followed by either a dimerization process or a disproportionation step. These latter transformations are followed by a second protonation event.

Enhancement of the radiation response of EMT-6 tumours by a copper octabromotetracarboranylphenylporphyrin

“…It is far more likely that its mode of action is similar to that proposed for Gd-Tex, whereby it is proposed that it reacts with hydrated electrons to prevent quenching of cell damaging hydroxyl radicals. The reduction potential of CuTCPBr is less positive [20.77 V vs saturated calomel electrode (SCE)] than that of Gd-Tex (20.32 V vs SCE), although this was assessed in dimethylformamide and not dichloromethane [29]. Nevertheless, CuTCPBr is retained in tumour tissue and produces a considerable modification of the radiation response with DMFs of between 1.29 and 1.84 depending on the dose administered and the formulation used.…”

Expanded porphyrins. Synthetic materials with potential medical utility

“…In contrast to the porphyrins and other polypyrrolic macrocycles reported in the literature, these aromatic, monoanionic ligands are known to form stable, nonlabile 1:1 complexes with a range of cations including those of the trivalent lanthanide series. This complexation ability, in conjunction with several other important attributes, including an unusual ease of reduction (E 1/2 < 0.08 V vs. NHE for 2 in aqueous media at pH 7) [13,14], a red-shifted lowest energy absorption maximum (l max 732 nm for 3) [15,16], and an ability to localize in neoplastic tissues and atheromatous plaque, has made several of these systems, notably complexes 2 and 3, attractive candidates for use in a range of medically important applications. These latter include such diverse and potentially bene®cial areas as X-ray radiation cancer therapy (XRT), photodynamic therapy for oncology (PDT), photoangioplasty (PA), and the light-based treatment of age-related macular degeneration (ARMD).…”

Electrochemical characterisation of bis(1,10-phenanthroline) gadolinium(III) trichloride formed in situ

“…For this reason, gadolinium organic complexes are important in Magnetic Resonance Imaging (MRI), since they alter the proton relaxation time of the nearby tissues, enhancing the contrast among different features. Electrochemical investigations of the radiation sensitizer Gadolinium (III) Texaphyrin (PCI-0120) complex show two quasi-reversible one-electron reductions at ~ -0.27 V and ~ -0.74 V vs. Ag/AgCl in deoxygenated DMF [7]. Provided the reduction potential for the Gd 3+ /Gd 2+ couple is much more negative than -0.27 V or -0.74 V, and the replacement of Gadolinium by other lanthanide ions leads to quite similar electrochemical behaviour, it is established that the reduction processes take place on the texaphyrin ligand, rather than at the metal centre.…”