Triarylphosphine-Coordinated Bipyridyl Ru(II) Complexes Induce Mitochondrial Dysfunction.

While cancer cells rely heavily upon glycolysis to meet their energetic needs, reducing the importance of mitochondrial oxidative respiration processes, more recent studies have shown that their mitochondria still play an active role in the bioenergetics of metastases. This feature, in combination with the regulatory role of mitochondria in cell death, has made this organelle an attractive anticancer target. Here, we report the synthesis and biological characterization of triarylphosphine-containing bipyridyl ruthenium (Ru(II)) compounds and found distinct differences as a function of the substituents on the bipyridine and phosphine ligands. 4,4'-Dimethylbipyridyl-substituted compound 3 exhibited especially high depolarizing capabilities, and this depolarization was selective for the mitochondrial membrane and occurred within minutes of treatment in cancer cells. The Ru(II) complex 3 exhibited an 8-fold increase in depolarized mitochondrial membranes, as determined by flow cytometry, which compares favorably to the 2-fold increase observed by carbonyl cyanide chlorophenylhydrazone (CCCP), a proton ionophore that shuttles protons across membranes, depositing them into the mitochondrial matrix. Fluorination of the triphenylphosphine ligand provided a scaffold that maintained potency against a range of cancer cells but avoided inducing toxicity in zebrafish embryos at higher concentrations, displaying the potential of these Ru(II) compounds for anticancer applications. This study provides essential information regarding the role of ancillary ligands for the anticancer activity of Ru(II) coordination compounds that induce mitochondrial dysfunction.

Long-Lived Photoluminescence of Molecular Group 14 Compounds through Thermally Activated Delayed Fluorescence.

Photoluminescent molecules exploiting the sizable spin-orbit coupling constants of main group metals and metalloids to access long-lived triplet excited states are relatively rare compared to phosphorescent transition metal complexes. Here we report the synthesis of three air- and moisture-stable group 14 compounds E(MePDPPh)2, where E = Si, Ge, or Sn and [MePDPPh]2- is the doubly deprotonated form of 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine. In solution, all three molecules exhibit exceptionally long-lived triplet excited states with lifetimes in the millisecond range and show highly efficient photoluminescence (Φ ≤ 0.49) due to competing prompt fluorescence and thermally activated delayed fluorescence at and around room temperature. Temperature-dependent steady-state emission spectra and photoluminescent lifetime measurements provided conclusive evidence for the two distinct emission pathways. Picosecond transient absorption spectroscopy allowed further analysis of the intersystem crossing (ISC) between singlet and triplet manifolds (τISC = 0.25-3.1 ns) and confirmed the expected trend of increased ISC rates for the heavier elements in otherwise isostructural compounds.

Redox Chemistry of Bis(pyrrolyl)pyridine Chromium and Molybdenum Complexes: An Experimental and Density Functional Theoretical Study.

The three- and four-membered redox series [Cr(MePDP)2]z (z = 1-, 2-, 3-) and [Mo(MePDP)2]z (z = 0, 1-, 2-, 3-) were synthesized to study the redox properties of the pincer ligand MePDP2- (H2MePDP = 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine). The monoanionic complexes were characterized by X-ray crystallography, UV/vis/NIR spectroscopy, and magnetic susceptibility measurements. Experimental and density functional theory (DFT) studies are consistent with closed-shell MePDP2- ligands and +III oxidation states (d3, S = 3/2) for the central metal ions. Cyclic voltammetry established multiple reversible redox processes for [M(MePDP)2]1- (M = Cr, Mo), which were further investigated via chemical oxidation and reduction. For molybdenum, one-electron oxidation yielded Mo(MePDP)2 which was characterized by X-ray crystallography, UV/vis/NIR, and magnetic susceptibility measurements. The experimental and computational data indicate metal-centered oxidation to a MoIV complex (d2, S = 1) with two MePDP2- ligands. In contrast, one- and two-electron reductions were found to be ligand centered resulting in the formation of MePDP•3- radicals, in which the unpaired electron is predominantly located on the central pyridine ring of the ligand. The presence of ligand radicals was established experimentally by observation of ligand-to-ligand intervalence charge transfer (LLIVCT) bands in the UV/vis/NIR spectra of the dianionic and trianionic complexes and further supported by broken-symmetry DFT calculations. X-ray crystallographic analyses of the one-electron-reduced species [M(MePDP)2]2- (S = 1, M = Cr, Mo) established structural indicators for pincer reduction and showed localization of the radical on one of the two pincer ligands. The two-electron-reduced, trianionic complexes (S = 1/2) were characterized by UV/vis/NIR spectroscopy, magnetic susceptibility measurements, and EPR spectroscopy. The electronic structures of the reduced complexes are best described as containing +III metal ions (d3) antiferromagnetically coupled to one and two radical ligands for the dianionic and trianionic species, respectively.