Probing the reactivity of the radiation sensitizer motexafin gadolinium (Xcytrin (R)) 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 ( R), gadolinium(III) texaphyrin) and several other water-soluble metallotexa phyrin complexes with N,N,N ' ,N ' -tetramethyl-p-phenylenediamine (TMPD) f or solvated electrons and hydroxyl radicals was studied using pulse radioly sis and by steady-state gamma -radiolysis. It was found that the one-electr on reduced forms (M-Tex(2+)) of the Gd(III), Eu(III), Dy(III), Yb(III), and Cd(II) texaphyrin complexes, after an initial reaction with hydrated elect rons, do not compete with TMPD for hydroxyl radicals formed under pulse rad iolytic conditions. By contrast, the reduced Y(III), In(III), Tm(III), and Lu(III) texaphyrin complexes do. These differences in competitive reactivit y 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 par ticular, the one-electron reduced product, Gd-Tex(2+), 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+) (mote xafin 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. Copyright (C) 2001 John Wiley & Sons, L td.