Reactivity of an extremenly sterically crowded monofunctional Pt complex, [Pt(1-MeC-N3)_3(H_2O)]~(2+) (1-MeC=1-methylcytosine), toward model nucleobases and selectivity toward guanine in single- and double-stranded deoxyoligonucleotides

摘要

Reactions of [Pt(1-MeC-N3)_3Cl]NO_3 (1-MeC-N3=1-methylcytosine, bound to Pt via N3) and the respective aqua species [Pt(1-MeC-N3)_3(H_2O)]~(2+) with the model nucleobases 9-ethylguanine (9-EtGH), 9-methyladenine (9-MeA), single-stranded 5'd(T_3GT_3), and double-stranded [5'd(GAGA_2GCT_2CTC)]_2 have been studied in solution by means of ~1H NMR spectroscopy, HPLC, and electrospray ionization mass spectrometry. Reactions are generally slow, in particular 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)_3Pt~(II) binds selectively to the terminal guanine only, probably because base fraying takes place at the duplex ends. The X-ray crystal structures of [Pt(1-MeC-N3)_3(9-EtG-N7)]ClO_4 centre dot 8H_2O (1b) and of [Pt(1-MeC-N3)_3(9-MeA-N7)](ClO_4)_2 centre dot 0.5H_2O as well as NMR spectroscopic studies of [Pt(1-MeC-N3)_3(9-EtGH-N7)](NO_3)_2 centre dot H_2O (1a) are reported. The tetrakis (nucleobase) complexes adopt a head-tail-head orientation of the three 1-MeC bases and an orientation of the fourth base (purine) that permits a maximum of intracomplex H bonds between exocyclic groups. As far as the guanine adduct (1a, 1b) is concerned, relative orientations of the four bases are identical in the model and in the oligonucleotide adduct.