Photophysics of bifunctional Ru(II) complexes bearing an aminoquinoline organic unit. Potential new photoprobes and photoreagents of DNA

[Ru(BPY)2POQ-Nmet]2+ and [Ru(TAP)2POQ-Nmet]2+ (1 and 3) are bifunctional complexes composed of a metallic unit linked by a flexible chain to an organic unit. They have been prepared as photoprobes or photoreagents of DNA. In this work, the spectroscopic properties of these bifunctional complexes in the absence of DNA are compared with those of the monofunctional analogues [Ru(BPY)2Phen]2+, [Ru-(BPY)2acPhen]2+, [Ru(TAP)2Phen]2+, and [Ru(TAP)2acPhen]2+ (2 and 4). The electrospray mass spectrometry and absorption data show that the quinoline moiety exists in the protonated and nonprotonated form. Although the bifunctional complex containing 2,2′-bipyridine (BPY) ligands exhibits photophysical properties similar to those of the monofunctional compounds, the bifunctional complex with 1,4,5,8-tetraazaphenanthrene (TAP) ligands behaves quite differently. It has weaker relative emission quantum yields and shorter luminescence lifetimes than the monofunctional TAP analogue when the quinoline unit is nonprotonated. This indicates an efficient intramolecular quenching of the 3MLCT (metal to ligand charge transfer) excited state of the TAP metallic moiety. When the organic unit is protonated, there is no internal quenching. In organic solvent, the nonquenched excited metallic unit (bearing a protonated quinoline) and the quenched one (bearing a nonprotonated organic unit) are in slow equilibrium as compared to the lifetime of the two emitters. In aqueous solution this equilibrium is faster and is catalysed by the presence of phosphate buffer. Flash photolysis experiments suggest that the intramolecular quenching process originates from a photoinduced electron transfer from the nonprotonated quinoline to the excited Ru(TAP)2 2+ moiety.

Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.