Cisplatin analogues. cis-Dichloroaminoacid-tert-butylamineplatinum(II) complexes and their adducts with guanosine

A series of compounds of formula cis-[PtCl₂- (aaH)(tba)] (1) (aaH, N-coordinate amino acid; tba, tert-butylamine) were synthesized. The circular dichroism spectra of these compounds show that the phenylalanine and proline derivatives have an anomalous conformation in water solution. By reaction with guanosine (guo) compounds 1 give cis- [Pt(aaH)(tba)(guo)₂]Cl₂ (2), in which infrared and nuclear magnetic resonance evidence suggest N(7) coordination of guo. NMR and circular dichroism data suggest that in 2 the two guanosine ligands are arranged head-to-head and form a right-hand helix. The bulkiness of the other ligands make rotation around the PtN(7) bonds a slow process on the NMR time scale. The chiroptical properties of 2 are not greatly influenced by the absolute configuration of the amino acid, the right-hand screw probably arising by some guo-guo interaction since the derivatives of 9-methylguanine with chiral amino acids do not possess this conformation.Preliminary results on the reaction between 1 and calf thymus DNA are also briefly reported. They show that the interaction of 1 with DNA is of a lower extent than in the case of cisplatin and its diamine analogues, and that it is independent on the configuration of the amino acids.All these results are briefly discussed and tentatively correlated with the low antitumor activity of 1 reported in a previous paper.