Probing the reactivity of the radiation sensitizer motexafin gadolinium (Xcytrin®) and a series of lanthanide(III) analogues in the presence of both hydroxyl radicals and aqueous electrons
Abstract
The competition of the radiation sensitizer motexafin gadolinium (Xcytrin®, gadolinium(III) texaphyrin) and several other water-soluble metallotexaphyrin complexes with N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) for solvated electrons and hydroxyl radicals was studied using pulse radiolysis and by steady-state γ-radiolysis. It was found that the one-electron reduced forms (M-Tex·+) of the Gd(III), Eu(III), Dy(III), Yb(III), and Cd(II) texaphyrin complexes, after an initial reaction with hydrated electrons, do not compete with TMPD for hydroxyl radicals formed under pulse radiolytic conditions. By contrast, the reduced Y(III), In(III), Tm(III), and Lu(III) texaphyrin complexes do. These differences in competitive reactivity toward .OH are rationalized in terms of the relative rates of protonation of the various singly reduced texaphyrins. In the case of Gd-Tex2+ in particular, the one-electron reduced product, Gd-Tex·+, protonates rapidly, producing a redox-inactive species that does not react appreciably with .OH. By contrast, the one-electron reduced product from, e.g., Lu-Tex2+ (motexafin lutetium), does. These results may explain, at least in part, why the Gd(III) texaphyrin functions as a radiation sensitizer in vivo, while the analogous Lu(III) complex does not.
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