Reactivity of an extremely sterically crowded monofunctional Pt complex, [Pt(1-MeC-N3)(3)(H2O)](2+) (1-MeC=1-methylcytosine), toward model nucleobases and selectivity toward guanine in single- and double-stranded deoxyoligonucleotides

Reactions of [Pt(1-MeC-N3)(3)Cl]NO3 (1-MeC-N3= 1-methylcytosine, bound to P t via N3) and the respective aqua species [Pt(1-MeC-N3)(3)(H2O)](2+) with t he model nucleobases 9-ethylguanine (9-EtGH), 9-methyladenine (9-MeA), sing le-stranded 5'd(T(3)GT(3)), and double-stranded [5'd(GAGA(2)GCT(2)CTC](2) h ave been studied in solution by means of H-1 NMR spectroscopy, HPLC. and el ectrospray ionization mass spectrometry. Reactions are generally slow, in p articular with the chloro species, and guanine is the only reactive base in the oligonucleotides. However, unlike (dien)Pt-II, which binds randomly to the guanines in the ds dodecamer, (1-MeC-N3)(3)Pt-II binds selectively to the terminal guanine only, probably because base fraying lakes place at the duplex ends. The X-ray crystal structures of [Pt(1-MeC-N3)(3)(9-EtGH-N7)]C lO4 . 8H(2)O (1b) and of [Pt(1-MeC-N3)(3)(9-MeA-N7)](ClO4)(2) . 0.5H(2)O as well as NMR spectroscopic studies of [Pt(1-MeC-N3)(3)(9-EtGH-N7)] (NO3)(2) . H2O (1a) are reported. The tetrakis(nucleobase) complexes adopt a head-t ail-head orientation of the three 1-MeC bases and an orientation of the fou rth base (purine) that permits a maximum of intracomplex H bonds between ex ocyclic groups. As far as the guanine adduct (1a, 1b) is concerned, relativ e orientations of the Four bases are identical in the model and in the olig onucleotide adduct.