Reaction of (C-(6-aminomethyl-pyridin-2-yl)methylamine)chloroplatinum(ii) with nucleosides and its biological activity

Abstract

1 H NMR and LC-ESI-MS studies of the interaction between nucleosides (adenosine, cytidine, guanosine, uridine and thymidine) and a monocation platinum(II) complex [Pt(C-(6-aminomethylpyridin-2-yl)methylamine)Cl]+ (1) shows it forms platinum(II) complexes with A, G and C at pH 6 and with T and U at pH 9. The X-ray structure of 1 as the hydrated chloride salt shows extensive hydrogen bonding. Amongst a series of related complexes 1 shows a strong interaction with DNA, demonstrated by inhibition of binding by the intercalator ethidium bromide, and moderate cytotoxicity. The interaction with nucleosides and the structural data suggest that 1 disrupts the DNA structure by coordinate covalent interaction and hydrogen bonding rather than simple intercalation.