Pulse radiolytic studies of metallotexaphyrins in the presence of oxygen: Relevance of the equilibrium with superoxide anion to the mechanism of action of the radiation sensitizer motexafin gadolinium (Gd-Tex(2+), Xcytrin)

Pulse radiolytic studies of aqueous solutions of four representative metall otexaphyrin complexes M-Tex(2+) (M = Gd(III), Lu(III), Dy(III), and Y(III)) , carried out in the presence of either dioxygen, or trimethyl-p-benzoquino ne (TMQ). It was found that all four of these M-Tex(2+) species set up an e quilibrium with superoxide and the singly reduced TMQ (TMQ(.-)) on the puls e radiolytic time scale. Rate constants for the forward (k(1)) and back (k( -t)) reactions of Gd-Tex(2+) with superoxide anions, at pH 8.5, were determ ined to be (9.8 +/- 1.5) x 10(6) M-t s(-1) and (3.4 +/- 0.5) x 10(6) M-1 an alogous rate constants were found to be (1.5 +/- 0.2) x 10(7) M-1 s(-1) and (3.7 +/- 0.6) x 10(6) M-1 s(-1) respectively. Equilibrium constants (K-kin ,), calculated from these kinetic parameters, were found to be 2.9 and 4.1 for Gd-Tex(2+) reacting with O-2(.-) (to produce Gd-Tex(.+) and O-2) and TM Q(.-) (to produce Gd-Tex(.+) and TMQ), respectively. Equilibrium constants for the M-Tex(2+) species reacting with O-2(.-) and TMQ(.-) were also deter mined from analysis of the absorption following establishment of the equili brium. The resulting values for Gd-Tex(2+) were found to be 6.8 and 10.7, r espectively. From these equilibrium constants, the redox potential for the M-Tex(2+)/M-Tex(.+) couples at pH 8.5 were estimated and found to be ca. -1 10 mV vs s(-1) and (3.4 +/- 0.5) x 10(6) M-1 NHE in the case of Gd-Tex'S s( -1), respectively. From these equilibrium constants, the redox potential fo r the M-Tex(2+)/M-Tex(.+) couples at pH 8.5 were estimated and found to ba ca. -110 mV vs NHE in the case of Gd-Tex(2+).