Modulation of Ligand Fluorescence by the Pt(II)/Pt(IV) Redox Couple

Abstract

The dangling carboxylic acid moiety of the known platinum(II) complex, [Pt(edma)Cl(2)] (edma = ethylenediaminemonoacetic acid), was functionalized via amide coupling chemistry with benzyl amine and dansyl ethylenediamine to afford the derivatives [Pt(edBz)Cl(2)] (1) and [Pt(edDs)Cl(2)] (2). Subsequent oxidation of these platinum(II) complexes with iodobenzene dichloride in DMF yielded the respective platinum(IV) analogues, [Pt(edBz)Cl(4)] (3) and [Pt(edDs)Cl(4)] (4). All four platinum complexes were characterized by multinuclear NMR spectroscopy, IR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis. In addition, compounds 1 and 3 were structurally characterized by X-ray crystallography. The photophysical properties of the compounds bearing the fluorescent dansyl moiety, 2 and 4, were evaluated. The emission quantum yields of 2 and 4 in DMF are 27% and 1.6%, respectively. This large difference in emission efficiency indicates that the platinum(IV) center in 4 is more effective at quenching the dansyl-based fluorescence than the platinum(II) center in 2. Time-dependent density functional theory calculations indicate that 4 has several low-lying singlet excited states that energetically lie below the primary radiation-accessible excited state of the dansyl fluorophore. These low-energy excited states may offer non-radiative decay pathways that lower the overall emission quantum yield. Treatment of 4 with biologically relevant reducing agents in pH 7.4 phosphate-buffered saline induces a 6.3-fold increase in emission intensity. These results demonstrate that 4 and future derivatives thereof may be useful for imaging the reduction of platinum(IV) complexes in living systems, chemistry of importance for future platinum-based anticancer drug strategies.

Fig. 1

Aromatic region of the ¹H NMR spectra of 1 (top) and 3 (bottom) obtained at 20°C and 400 MHz in DMF-d₇. The asterisk marks the signal due to the solvent.

Fig. 2

ORTEP diagrams of 1. The intermolecular Pt-Pt interaction is shown at the right. Ellipsoids are drawn at 50% probability levels.

Fig. 3

ORTEP diagram of 3. Ellipsoids are drawn at the 50% probability level.

Fig. 4

Cyclic voltammograms of 3 (bottom) and 4 (top) measured at a scan rate of 100 mV/s in DMF with 0.1 M (Bu₄N)(PF₆) as the supporting electrolyte. The potential is reported vs Ag/AgCl.

Fig. 5

Frontier Kohn-Sham molecular orbital diagram for 2 (left) and 4 (right).

Fig. 6

Emission spectra of 4 before (black line) and after addition of 10-fold excess of glutathione (red dashes) in pH 7.4 phosphate-buffered saline. The small peak at 680 nm arises from scattered excitation light (λ_ex = 340 nm).

Scheme 1

Scheme 2

Scheme 3