X-ray Structure of Cytotoxic trans-[PtCl2(dimethylamine)(isopropylamine)]: Interstrand Cross-Link Efficiency, DNA Sequence Specificity, and Inhibition of the B−Z Transition

Publisher Website
Google Scholar
Abstract
We report here the X-ray structure of cytotoxic trans-[PtCl2(dimethylamine)(isopropylamine)]. This trans-platinum compound crystallizes in the monoclinic system, with Z = 8, in the spatial group C2/c with unit cell parameters a = 19.862(17) Å, b = 6.581(3) Å, c = 18.563(3) Å, α = 90°, β = 119.16(3)°, γ = 90°, V = 2119(2) Å3, ρ = 2.321 Mg/m3, R = 0.0505, and Rw = 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 containing different aliphatic amines. The DNA binding mode of trans-[PtCl2(dimethylamine)(isopropylamine)] may be a consequence of the spatial disposition of the dimethylamine and isopropylamine ligands around the trans-Pt(II) center. We have found that trans-[PtCl2(dimethylamine)(isopropylamine)] readily forms DNA interstrand cross-links. In addition, the compound shows binding affinity toward alternating purine−pyrimidine sequences and inhibits the B−Z transition. These particular DNA binding properties might be related to the capacity of trans-[PtCl2(dimethylamine)(isopropylamine)] for inducing some selective killing in a H-ras overexpresssing cell line.