Photoluminescent DNA binding and cytotoxic activity of a platinum(II) complex bearing a tetradentate β-diketiminate ligand

Abstract

A platinum(II) complex of a monoanionic, tetradentate β-diketiminate (BDI) ligand with pendant quinoline arms, BDI(QQ)H, is reported. The complex, [Pt(BDI(QQ))]Cl, is emissive in DMSO, but non-emissive in aqueous buffer. Upon binding DNA in buffer, however, a 150-fold turn-on in emission intensity occurs. Dynamic light scattering and (1)H NMR spectroscopy indicate that [Pt(BDI(QQ))]Cl forms non-emissive aggregates in aqueous solution; DNA-binding disperses the aggregates leading to the large emission turn-on response. The cytotoxic activity of the complex, measured in two cancer cell lines, is comparable to or better than that of the established anticancer drug cisplatin.

Fig. 1

X-ray crystal structure of [Pt(BDI^QQ)]⁺ (left). Ellipsoids are drawn at the 50% probability level. Unlabeled grey and white ellipsoids correspond to carbon and hydrogen atoms, respectively. Intermolecular stacking interaction observed in the crystal lattice (right).

Fig. 2

UV-vis spectra of [Pt(BDI^QQ)]Cl in DMSO (black, dashed) and aqueous buffer (red, solid, pH 7.4, 10 mM Tris, 10 mM NaCl). The dotted blue line is the simulated UV-vis spectrum from TD-DFT calculations with a DMSO solvation model. The solid blue bars represent individual singlet transitions, and the associated EDDMs for selected transitions are displayed.

Fig. 3

UV-vis (top) and emission (bottom) spectral changes of [Pt(BDI^QQ)]Cl upon the addition of up to 500 equiv. nucleotide of CT-DNA in buffer (pH 7.4, 10 mM Tris, 10 mM NaCl) after a 16 h equilibration period. The black arrows mark the spectral changes as the concentration of CT-DNA increases. The inset shows a plot of [DNA] vs. absorbance at 560 nm.

Scheme 1

Synthesis of [Pt(BDI^QQ)]Cl.