The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin

Abstract

The effect of transition metal ions on the electrochemistry of 6-methoxy-5,8-quinolinedione (L1), 7-amino-6-methoxy-5,8-quinolinedione (L2) and the antitumor antibiotic streptonigrin (SN) was studied. In 10% methanol/water, the one-electron reduction of quinones L1 and L2 to the corresponding semiquinones is shifted to more positive potentials upon addition of one equivalent of Zn(II), Ni(II), Co(II) or Cd(II) and is consistent with formation of a 1:1 complex involving the quinone(N) and adjacent quinone(O). Similar results are observed for Cu(II) and Mn(II), but the redox chemistry is also complicated by metal-based redox chemistry. The addition of further equivalents of M(II) results in a number of different coordination and electrochemical processes including formation of 1:1 and 2:1 complexes of the quinone, semiquinone and dianion. Under similar conditions, the 1:1 SN 2,2′-bipyridyl metal complex undergoes a reversible one-electron reduction to the semiquinone. The redox potential of the quinone in SN was shifted positive in the presence of the metal ions, but both the magnitude of the shift, and the relative influence of the metals was different to ligands L1 and L2. The changes in redox chemistry of SN compared with L1 and L2 are consistent with the formation of the 2,2′-bipyridyl complexes in which there is weaker coordination to the quinone(O) in ring A of SN. These results suggest that in vivo, metal ions such as Zn(II), Cu(II) and Mn(II) facilitate the initial reduction of streptonigrin to the semiquinone by capturing the semiquinone after SN is reduced by biological reductants.