Synthesis and characterization of antitumor-active platinum 2,2-dimethyl- 1,3-diaminopropane compounds. Crystal and molecular structure of (malonato)(2,2-dimethyl-1,3-diaminopropane)platinum(II)

Article abstract of DOI:10.1021/ic50208a011

The synthesis and characterization of a series of platinum compounds containing 2,2-dimethyl-1,3-diaminopropane (DMDAP) are described. The compounds are Pt(DMDAP)X₂ with X₂ = Cl₂, Br₂, I₂, or malonate and Pt(DMDAP)Cl₄. The crystal structure of the malonate compound has been determined from three-dimensional single-crystal X-ray data. The complex crystallizes in space group P2₁/m of the monoclinic system with two formula units in a unit cell of dimensions a = 5.807 (2) ?, b = 9.980 (5) ?, c = 9.667 (2) ?, and β = 96.31 (3)°. The structure was solved by standard Patterson and Fourier methods and refined by full-matrix least-squares techniques to a value of the conventional R_F factor of 0.021 (R_wF = 0.034) by using 1260 observed reflections. The molecule lies on a crystallographic mirror plane passing through the platinum atom, the methylene group of the malonate ion, and the C(CH₃)₂ group of the amine. The coordination geometry around Pt is square planar with two oxygen atoms at 2.029 (4) ? and two nitrogen atoms at 2.022 (4) ?. The N-Pt-N angle is 97.2 (2)°, and the O-Pt-O angle is 90.1 (2)°. The crystal structure consists of layers perpendicular to the c axis in which the molecules are pseudohexagonally stacked and coupled through hydrogen bonds of the type N-H?O. The Pt-amine chelate ring adopts a chair conformation strongly flattened at the PtN₂ end while the Pt-malonate chelate ring has a boat conformation. The chloro compounds and the malonate compound show significant activity against the L-1210 leukemia in mice. Some remarks concerning the relation between structure and activity of the platinum compounds are made.