Synthesis and characterization of monodeoxynucleotide tethered platinum-(II) and -(IV) complexes

Improved syntheses of platinum-(II) and -(IV) complexes with pendant hydrox y groups have been elaborated. When the hydroxy groups of the platinum(II) complexes were subjected to phosphoramidite coupling agents to synthesize t he corresponding phosphoramidites, intramolecular displacement of the chlor ide on the platinum by the incoming phosphoramidite group occurred. This ge nerated chloro{N-2-[(2-cyanoethyl)(diisopropylamino)phosphinoxy]ethylenedia mine}platinum(II) chloride, which was characterized by a number of physical techniques including X-ray diffraction study. It crystallized from methano l-diethyl ether as white block crystals. Single crystal X-ray analysis reve aled that the platinum adopts a four-co-ordinate square planar configuratio n, provided by the two amine nitrogens, one phosphorus, and one chloride io n. The co-ordination of the phosphoramidite group prevents further manipula tion of this group to connect with other hydroxy groups. Intramolecular ele ctron transfer reaction occurred when the platinum(IV) complexes were used in the same reaction. A new strategy has been developed to couple monodeoxy nucleotides with the hydroxy groups of the tethered platinum-(Ir) and -(Iv) complexes through the use of monodeoxynucleotide phosphoramidite agents. E very peak in the H-1, C-13-{H-1} and Pt-195 NMR spectra for all the compoun ds reported has been assigned through the combination of 1-D H-1, C-13-{H-1 }, 2-D COSY, XHCORR (heteronuclear chemical shift correlation), HMQC (heter onuclear multiple quantum correlation), and the comparison of chemical shif ts among analogs.