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(<i>C</i>-(6-aminomethylpyridin-2-yl)methylamine)Cl]⁺ (<b>1</b>) 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 <b>1</b> as the hydrated chloride salt shows extensive hydrogen bonding. Amongst a series of related complexes <b>1</b> 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 <b>1</b> disrupts the DNA structure by coordinate covalent interaction and hydrogen bonding rather than simple intercalation.