Currently used platinum antitumor drugs, such as cisplatin (cis-[PtCl2ACHTUNGTRENNUNG (NH3) 2]) and oxaliplatin ([PtACHTUNGTRENNUNG (oxalate) ACHTUNGTRENNUNG (R, R-DACH)])(DACH= 1, 2-diaminocyclohexane), are believed to trigger apoptotic cell death by a cascade of cellular events induced by an initial reaction with DNA.[1, 2] This reaction yields predominantly covalent crosslinks between adjacent guanine bases, which produce a bend in the DNA double-helix.[3] The crosslinks are generally inert and thus persistent; nevertheless some examples have been identified where an initially formed crosslink rearranges to another lesion.[4] We report here a remarkable case of such a rearrangement where the initial duplex d (C1C2T3T4G* 5G* 6T7C8T9C10)-d (G11A12G13A14C15C16A17A18G19G20)(1)(G* bases crosslinked by PtACHTUNGTRENNUNG (S, S-DACH) 2+, the enantiomer of PtACHTUNGTRENNUNG (R, R-DACH) 2+ occurring in oxaliplatin) rearranges to the interstrand-crosslinked species d (C1C2T3T4G5G* 6T7C8T9C10)-d (G* 11A12G13A14C15C16A17A18G19G20)(2). 2 has an unprecedented structure with a head-to-tail orientation of the platinated bases G* 6 and G* 11 and a side-on interaction between G* 11 and the methyl group of T7. This intrastrand-to-interstrand rearrangement is a new demonstration of the kinetic instability of PtÀN bonds in strained structures. The initial aim of our work was to evaluate the impact of the ligand chirality {PtACHTUNGTRENNUNG (R, R-DACH) 2+ versus PtACHTUNGTRENNUNG (S, S-DACH) 2+} on the structure of the intrastrand-crosslinked duplex 1. The S, S enantiomer, as compared to the R, R enantiomer, has lower antitumor and much greater mutagenic activities.[5] 1 was obtained by reaction of [PtACHTUNGTRENNUNG (NO3) 2ACHTUNGTRENNUNG (S, S-DACH)] with the d (C1C2T3T4G5G6T7C8T9C10) single-strand and hybridization of the purified G* 5G* 6-platinated singlestrand with the complementary strand. In the course of the NMR investigation, we observed the appearance of a second set of NMR signals belonging to a new species (2) which formed at the expense of 1 and achieved, within one week, a concentration comparable to that of 1, as judged from the cytosine H5–H6 crosspeak volumes. Electrophoretic studies (see Experimental Section) indicated that the mixture contained an interstrand-crosslinked species, and this conclusion was supported by the observation that, upon heating to 408C, the peaks of 1 disappear completely (as expected for an intrastrand-crosslinked duplex of this size),[6] whereas those of 2 persist indicating that it is a duplex stabilized by covalent bonds. In the course of one year, the fraction of 2 increased to virtually 100%. In spite of the structural perturbation caused to the DNA double-helix by this unusual interstrand crosslink (vide infra), the sequential connectivities among sugar and base protons, typical of B-DNA, are largely conserved in 2, enabling an assignment based on standard methods (Table S1 in the Supporting Information).[7] A 500 ms NOESY spectrum of an approximately 1: 1 mixture of 1 and 2 is shown in Figure 1. The spectrum of the intrastrand-crosslinked species 1 is characterized by the typical low-field signal of the H8 proton of the platinum-bound 5’-guanine, G* 5, around 8.7 ppm, which has a crosspeak with the H8 of the other [a] Dr. K. Kubícek, J. Monnet, Prof. J. Kozelka Masaryk University