Formation of Adenine−N3/Guanine−N7 Cross-Link in the Reaction of trans-Oriented Platinum Substrates with Dinucleotides

The reactions of the anticancer complex trans-[PtCl2{(E)-HNC(OMe)Me}2] (trans-EE) with a series of ribo and deoxyribodinucleotides have been studied by HPLC and 2D [1H, 15N] 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.