Crystal and Molecular Structure of cis-[Pt(NH₃)₂{d(pGpG)}], the Principal Adduct Formed by cis-Diamminedichloroplatinum(II) with DNA

The crystal and molecular structures of cis-[Pt(NH₃)₂{d(pGpG)}], the major adduct of the antitumor drug cisolatin covalently bound to its putative target on DNA, are reported. In the asymmetric unit, intermolecular hydrogen bonding and stacking interactions hold four crystallographically independent molecules together in a tightly packed aggregate, providing four examples of alternate conformations for this biologically important molecule. Tetrameric aggregates are separated from one another in the unit cell by solvent channels of varying diameters running parallel to the crystallographic axes. The conformations of the dinucleotides appear to be largely dependent on the requirements of platinum coordination. Thus, for each crystallographically independent molecule, platinum is coordinated in a square-planar mode to two cis ammine ligands and two guanine N7 atoms from the same dinucleotide, forcing the guanine bases to destack with resulting Gua/Gua dihedral angles ranging from 76.2 (5)° to 86.8 (6)°. Concomitant changes occur in torsion angles x at the 5'- and 3'-ends of the dinucleotide, compared to the values typically found in DNA. The constraints of the dinucleotide backbone do, however, maintain the head-to-head orientation of the guanine bases. Overall, the backbone torsion angles at the 5'-end of each molecule resemble those in A-DNA. Backbone torsion angles at the 3'-ends are less easily categorized. In at least three of the four molecules, an intramolecular hydrogen bond occurs between a proton of an ammine ligand and an oxygen atom of the terminal 5'-phosphate, as had been previously predicted from molecular mechanics calculations. The molecule cis-[Pt(NH₃)₂{d(pGpG)}] crystallizes in two forms, crystal type 1 having a = 31.326 (8) Å, b = 35.679 (9) Å, c = 19.504 (4) Å, Z = 16, space group P2₁2₁2 and crystal type 2 with a = 30.55 Å, b = 33.90 Å, c = 41.25 Å, Z = 32, space group C222₁. In the former crystal type, which forms the basis of the present discussion, 27 water and two glycine molecules as well as four platinated DNA fragments were located in the asymmetric unit.