X-ray structure of cytotoxic trans-[PtCl2(dimethylamine) (isopropylamine)]: Interstrand cross-link efficiency, DNA sequence specificity, and inhibition of the B-Z transition

We report here the X-ray structure of cytotoxic trans-[PtCl2(dimethylamine) (isopmpylamine)]. This trans-platinum compound crystallizes in the monoclin ic system, with Z = 8, in the spatial group C2/c with unit cell parameters a = 19.862(17) Angstrom, b = 6.581(3) Angstrom, c = 18.563(3) Angstrom, alp ha = 90 degrees, beta = 119.16(3)degrees, gamma = 90 degrees, V = 2119(2) A ngstrom(3), rho = 2.321 Mg/m(3), R = 0.0505, and R-w = 0.1166 on the basis of 2339 independent reflections. To our knowledge this is the first report of the crystal structure of a biologically active trans-platinum compound c ontaining different aliphatic amines. The DNA binding mode of trans-[PtCl2( dimethylamine)(isopropylamine)] may be a consequence of the spatial disposi tion of the dimethylamine and isopropylamine ligands around the trans-Pt(II ) center. We have found that trans-[PtCl2(dimethylamine)(isopropylamine)] r eadily forms DNA interstrand cross-links. In addition, the compound shows b inding affinity toward alternating purine-pyrimidine sequences and inhibits the B-Z-transition. These particular DNA binding properties might be relat ed to the capacity of trans-[PtCl2(dimethylamine)(isopropylamine)] for indu cing some selective killing in a H-ras overexpresssing cell line.