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

Abstract

Improved syntheses of platinum-(II) and -(IV) complexes with pendant hydroxy groups have been elaborated. When the hydroxy groups of the platinum(II) complexes were subjected to phosphoramidite coupling agents to synthesize the corresponding phosphoramidites, intramolecular displacement of the chloride on the platinum by the incoming phosphoramidite group occurred. This generated chloro{N-2-[(2-cyanoethyl)(diisopropylamino)phosphinoxy]ethylenediamine}platinum(II) chloride, which was characterized by a number of physical techniques including X-ray diffraction study. It crystallized from methanol–diethyl ether as white block crystals. Single crystal X-ray analysis revealed that the platinum adopts a four-co-ordinate square planar configuration, provided by the two amine nitrogens, one phosphorus, and one chloride ion. The co-ordination of the phosphoramidite group prevents further manipulation of this group to connect with other hydroxy groups. Intramolecular electron transfer reaction occurred when the platinum(IV) complexes were used in the same reaction. A new strategy has been developed to couple monodeoxynucleotides with the hydroxy groups of the tethered platinum-(II) and -(IV) complexes through the use of monodeoxynucleotide phosphoramidite agents. Every peak in the ¹H, ¹³C-{¹H} and ¹⁹⁵Pt NMR spectra for all the compounds reported has been assigned through the combination of 1-D ¹H, ¹³C-{¹H}, 2-D COSY, XHCORR (heteronuclear chemical shift correlation), HMQC (heteronuclear multiple quantum correlation), and the comparison of chemical shifts among analogs.