Structure of a novel drug-nucleic acid crystalline complex: 1, 10-phenanthroline-platinum (II) ethylenediamine--5'-phosphoryl-thymidylyl(3'-5') deoxyadenosine.

1,10-Phenanthroline-platinum (II) ethylenediamine (PEPt) forms a 1:2 crystalline complex with 5'-phosphorylthymidylyl (3'-5') deoxyadeno sine (d-pTpA). Crystals are monoclinic, P2, with a = 10.204 A, b = 24.743 A, c = 21.064 A, Beta = 94.6 degrees. The structure has been determined by Patterson and Fourier methods, and refined by least squares to a residual of 0.128 on 2,367 observed reflections. PEPt molecules form sandwich-like stacks with adenine-thymine hydrogen-bonded pairs along the alpha axis. Intercalation in the classic sense is not observed in this structure. Instead, d-pTpA molecules form an open chain structure in which adenine-thymine residues hydrogenbond together with the reversed Hoogsteen type base-pairing configuration. Deoxyadenosine residues exist in the syn conformation and are C3' endo and C1' exo. Thymidine residues are in the high anti conformation with C2' endo puckers. The structure is heavily hydrated, forming a channel-like water network along the alpha axis. Other features of the structure are described.