COMPARISON OF THE REACTIVITY OF CIS-[RUCL2(DMSO)(4)] AND TRANS-[RUCL2(DMSO)(4)] TOWARDS NUCLEOSIDES

Electrospray ionization mass spectrometry and H-1 NMR spectroscopy wer e used to examine the reactions of cis-[RuCl2(DMSO)(4)] and trans-[RuC l2( DMSO)(4)] with deoxynucleosides. Both complexes react with 2'-deox yguanosine to give identical products, two diastereoisomers containing a single nucleoside coordinated to ruthenium, and a bis adduct contai ning two coordinated nucleosides. Coordination of the nucleoside to ru thenium is via the N-7 atom in each complex. Trans-[RuCl2(DMSO)(4)] re acts with 2'-deoxyadenosine to give a pair of diastereoisomers in whic h the nucleosides are coordinated via their N-1 atoms. Cis-[RuCl2(DMSO )(4)] reacts less extensively with 2'-deoxyadenosine to give a mixture of products, each of which contains a single 2'-deoxyadenosine ligand coordinated to the metal through the N-1 atom. Trans-[RuCl2(DMSO)(4)] was found to react only to a small extent with 2'-deoxycytidine under conditions similar to these used for 2'-deoxyguanosine and 2'-deoxyad enosine, and not at all with thymidine, even after prolonged periods. The implications of these results for the mechanisms of antitumour act ivity of these two complexes are discussed. (C) 1998 Elsevier Science S.A. All rights reserved.