Kinetics of formation and stability of {Pt(dien)}2+ complexes with octamer and 14-mer DNA oligonucleotides containing a GG sequence

Reaction of [Pt(dien)Cl]+ (1) with the 14-mer oligonucleotide 5′-d(ATACATGGTACATA) (I) gave rise to two major species which corresponded to the 5′-G and 3′-G platinated monofunctional adducts, and a minor amount of the bis-platinated adduct formed during the later stages of the reaction. The reaction of (1) with the related octamer 5′-d(ATACATGG) (II) was also investigated. Kinetic data obtained by HPLC showed that the 5′-G and 3′-G bases of the 14-mer oligonucleotide were platinated at similar rates: the second-order rate constant is 53×10–2 M–1 s–1 at 298 K in 0.1 M NaClO4. However, the platination rate of 5′-G of the octamer (II) (k=69×10–2 M–1 s–1) was enhanced by a factor of three compared to the rate of platination at 3′-G (k=22×10–2 M–1 s–1). All the adducts were separated by HPLC and characterized by NMR spectroscopy, enzymatic digestion and MALDI-TOF mass spectrometry. 1H and 15N NMR shifts suggest that there are distinct conformational differences between 14-mer duplexes platinated at 5′-G (I5′ds) and 3′–G (I3′ds). Molecular mechanics modelling indicates that rotation around the Pt-N7 bond is more restricted in the case of the 5′-G adduct than in that of the 3′-G adduct. The binding of {Pt(dien)}2+ to 5′-GN7 and 3′-GN7 in the monofunctional adducts of (I) was shown to be reversible upon the addition of high concentrations of chloride ions.