INTERACTION OF TIN(IV) WITH DOXORUBICIN

The first study of the interaction of tin(IV) with the anticancer anti biotic 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 Sn-119 NMR spectrosco py. Reactions with modified anthracyclines show that the alpha-ketol s ide chain at C-9 is essential for interaction, while the quinone chrom ophore is not involved in binding, as inferred from optical spectrosco py. Proton NMR data suggest that binding to the C-9 side chain involve s enolization at C-13-C-14. The two-dimensional total correlation spec tra indicate that the daunosamine moiety of doxorubicin can be involve d in Sn-IV binding with formation of several time-dependent species. T his was verified by H-1 and Sn-119 NMR studies of Sn-IV-daunosaminide hydrochloride systems. These findings suggest that Sn-IV can bind to d oxorubicin at two sites: the C-9 alpha-ketol chain, probably after eno lization, and the sugar ring at the 4'-OH and 3'-NH2 positions. This i s the first report of metal binding to doxorubicin at the C-9 side cha in.