Robust structure and reactivity of aqueous arsenous acid-platinum(II) anticancer complexes

Abstract

The first molecular adducts of platinum and arsenic based anticancer drugs - arsenoplatins - show unanticipated structure, substitution chemistry, and cellular cytotoxicity. The Pt^II-As^III bonds in these complexes are stable in aqueous solution and strongly influence the lability of the trans ligand.

Keywords: X-ray diffraction; antitumor agents; arsenic; drug design; platinum.

Figure 1

a) Thermal ellipsoid plots of complex 1a (1 crystallizes in two crystal systems) and b) complex 2. Solvent molecules have been omitted for clarity. The plots are drawn at 50 % probability level.^[10]

Figure 2

Thermal ellipsoid plot of 3. The plot is drawn at 50 % probability level.

Figure 3

a) ¹H-¹³C HSQC NMR spectrum of 3 (with S¹³C¹⁵N) in [D₆]DMSO, acquired at 25 °C at 600 MHz ¹H with high resolution in the indirect (¹³C) dimension to distinguish the methyl resonances of the N- and S-isomers; b) ¹⁹⁵Pt NMR spectrum of 3 (with S¹³C¹⁵N) in [D₆]DMSO, referenced indirectly to ¹H TMS such that Na₂¹⁹⁵PtCl₆ resonates at 0.0 ppm. The 456 Hz splitting of the ¹⁹⁵Pt peak at -3724 ppm arises from scalar coupling to the SCN ¹⁵N.

Figure 4

Dose response curves for a) ovarian cisplatin resistant A2780^CP, b) colon HCT-116, and c) glioblastoma U-87 cancer cell lines after exposure to 1 cisplatin, and As₂O₃.