Interaction of tin(IV) with doxorubicin‡

Abstract

The first study of the interaction of tin(IV) with the anticancer antibiotic doxorubicin in N,N-dimethylformamide (dmf) solution is reported. Electronic absorption spectroscopy showed that reaction of the drug with SnCl₄ is time dependent and involves the initial formation of a 1∶1 complex. The strong binding was also shown by ¹¹⁹Sn NMR spectroscopy. Reactions with modified anthracyclines show that the α-ketol side chain at C⁹ is essential for interaction, while the quinone chromophore is not involved in binding, as inferred from optical spectroscopy. Proton NMR data suggest that binding to the C⁹ side chain involves enolization at C¹³–C¹⁴. The two-dimensional total correlation spectra indicate that the daunosamine moiety of doxorubicin can be involved in Sn^IV binding with formation of several time-dependent species. This was verified by ¹H and ¹¹⁹Sn NMR studies of Sn^IV–daunosaminide hydrochloride systems. These findings suggest that Sn^IV can bind to doxorubicin at two sites: the C⁹ α-ketol chain, probably after enolization, and the sugar ring at the 4′-OH and 3′-NH₂ positions. This is the first report of metal binding to doxorubicin at the C⁹ side chain.