Study of the binding of cis- and trans-dichlorodiammineplatinum(II) to calf thymus DNA by extended x-ray absorption fine structure spectroscopy

Abstract

The complex cis-dichlorodiammineplatinum(II) (DDP) is an active antitumor drug while the trans-DDP isomer is ineffective, a result that may reflect differences in their ability to bind DNA.[1-5] While various chemical and physical techniques have been used to explore the interactions of these platinum compounds with DNA, there appears to be no direct structural information about the resulting platinum-DNA complex. Recent crystallographic study[5c] of the blue compound formed between cis-diammineplatinum and a-pyridone (1) suggested[5b] that thymine (2, R = CH3) and guanine (3) bases in DNA might bridge two cis-diammineplatinum units using the deprotonated amide nitrogen and the exocyclic oxygen as donor atoms. The resulting complex would have a short Pt-Pt distance, 2.5-3.2 A, depending upon the platinum oxidation state. To test this possibility and to provide information about the binding sites ofDDP, samples of cis- and trans-[Pt(NH3)iC!i] bound to calf thymus DNA, 4 and 5, respectively, were prepared and studied by extended x-ray absorption fine structure (EXAFS) spectroscopy.