Intrinsically fluorescent cytotoxic cisplatin analogues as DNA marker molecules.

Two square planar derivatives of Pt(en)Cl(2) with intrinsic fluorescence in aqueous solution at room temperature, with quantum yields (Phi) 0.11 and 0.10, respectively, have been synthesized and characterized as [Pt(en)(CG)Cl] (Complex 1) and [Pt(en)(CG)(2)] (Complex 2) (en = ethylenediamine, CG = cholylglycinate). Complexes 1 and 2 exchange just one ligand (chloride or cholylglycinate, respectively) when reacted with water or 5'-GMP to give the same chemical species. After reaction with DNA oligonucleotides or DNA plasmids, they show enhanced emission in the visible region, which lasts for long periods of time and makes them potentially useful DNA marker molecules. Incubation with nucleated blood cells followed by microscopic analyses revealed that they enter the cells within minutes of exposure, selectively stain the DNA, and persist after more than 48 h of exposure. Complexes 1 and 2 display cell cycle phase-independent cytotoxic activity against cisplatin-resistant CHO (Chinese hamster ovarian) tumor cells, with an early onset of their effects. Their slightly different biological effects, as compared to cisplatin, are considered to be linked to the bile acids and their vector properties and to the preferential formation of monoadducts.