The reactions of the anticancer complex trans-[PtCl{(E)-HN=C(OMe)Me}(2)] (trans-EE) with a series of ribo and deoxyribodinucleotides have been studied by HPLC and 2D [H-1, N-15] HMQC NMR spectroscopy and compared with those of the inactive trans isomer of cisplatin, trans-[PtCl2(NH3)(2)] (trans-DDP). Reactions of trans-EE with r(ApG) and d(ApG) take place through solvolysis of the starting substrate and subsequent formation of trans G-N7/monochloro and G-N7/monoaqua adducts. Slowly, the monofunctional adducts evolve to a bifunctional adduct forming an unprecedented and unexpected A-N3/G-N7 platinum cross-link spanning two trans positions. For stereochemical reasons, trans platinum complexes cannot form N7/N7 cross-links between adjacent purines in di- or polynucleotides. For the reverse sequence r(GpA), no chelate structure was formed even after a two-week reaction. The reaction of trans-DDP with r(ApG) produces many more products than the analogous reaction with trans-EE. One of these products was identified as the A-N3/G-N7 trans-chelate.