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

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 - Tex 2+ 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 - Tex 2+ (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.