The one-electron reduction potential of 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine): a hypoxia-selective bioreductive drug.

The one-electron reduction potential of 3-amino-1,2,4-benzotriazine 1,4-dioxide, tirapazamine (SR 4233) in aqueous solution has been determined by pulse radiolysis. Reversible electron transfer was achieved between radiolytically-generated one-electron reduced radicals of tirapazamine (T), and quinones or benzyl viologen as redox standards. The reduction potential Em7(T/T-) was -0.45 +/- 0.01 V vs. NHE at pH 7 From the pH dependence of the reduction potential, pKa = 5.6 +/- 0.2 was estimated for the tirapazamine radical, a value similar to the pKa determined by other methods.