Intramolecular aromatic-ring stacking interaction of ternary Zn (UTP)L~(2-) complexes

摘要

THE mechanism of the action of the classic platinum antitumor drugs can be interpreted according to their bidentate, bifunctional interaction with the DNA of the tumor cell, resulting in inhibition of the DNA replication . Recently, it was found thata new class of compounds with the general formula cts-[Pt(NH_3)_2(N-het)Cl]Cl (N-het is a heteroaromatic N-base like pyri-dine) show effective antitumor activities. However, two possible mechanisms of action were proposed for the class of antitumor drugs, One possible mechanism would be that through loss of ammonia, cis-[Pt(NH_3)(N-het) ]~(2+) would be generated in vivo, which would then be the active species. Another possible interaction might be monofunctional binding to DNA, with N-het acting as an intercalator. But recently it was suggested by Reedijk et al. that no [Pt(NH_3) (N-het)]~(2+) would be formed upon ammonia released from the drugs, and hence the first mechanism is incorrect, In addition, the second mechanism of binding and intercalationhas not been proved by experimental data. Therefore, study on the intramolecular stacking interaction of ternary M(NTP) (N-het)~(2-) complexes may give helpful information about the mechanism. In this work, the stability of the ternary Zn (UTP) L~(2-) complexes, where UTP = Uridine 5 ' - triphosphate and L = benzimidazole ( Bi ) or isoquinoline ( Iq ) , has been studied by potentiometric pH titration.