Ferrocenyl-based di- and trinuclear lanthanide complexes: solid state structures, (spectro)electrochemical and DFT studies.

Dinuclear and trinuclear ferrocenylcarboxylato-bridged lanthanide complexes of type [Ln(µO:κ2OO'-O2CFc)(O2CFc)2(H2O)(dmf)]2·(dmf)2 (Ln = Sm (2), Eu (3), Gd (4), Tb (5); Fc = Fe(η5-C5H4)(η5-C5H5)), and novel [Bu4N][Ln3(µ-O2CFc)3(µO:κ2OO'-O2CFc)3(O2CFc)3(µ3-OH)]·[Bu4N]Cl (Ln = Gd (6), Tb (7)) were prepared by the reaction of [LnCl3·6H2O] (synthesis of 2-5) or LnCl3 (synthesis of 6, 7) with FcCO2H (1) in the ratio of 1 : 3. As evidenced by single crystal X-ray structure determination, in 2-5 the lanthanide ions are connected by symmetric FcCO2 units. In addition, two ferrocenylcarboxylato groups are µ-bridged to LnIII. Each LnIII ion is coordinated by nine oxygen donor atoms derived from one H2O, one dmf and three carboxylates. The latter are found in chelating κ2 and bridging µ,κ3 coordination modes. Complexes 6 and 7 assemble three LnIII cores around a central µ3-netting hydroxide and nine FcCO2 entities. A combination of κ2, µ,κ2 and µ,κ3 coordination modes results in an eight-fold coordination sphere for each metal, which is best described as bicapped trigonal prismatic. IR spectroscopy confirms the chelating and bridging motifs. Electrochemical studies of complexes 2-7via cyclic voltammetry (CV) and square-wave voltammetry (SWV) showed one redox event between E°' = 250 and 260 mV vs. FcH/FcH+ for 2-5 with all six FcCO2 redox events superimposed. Complexes 6 and 7 show a total of three events in the CV with the oxidations of the nine FcCO2 units occurring in close proximity. Deconvolution of individual redox events correlates well with the mononuclear complex [Bu4N][Gd(O2CFc)4]. UV-Vis/NIR spectroelectrochemical measurements of 7 did not reveal electron transfer between either Fc units, nor the coordinated lanthanides and resembled the absorption behavior of [Bu4N][Tb(O2CFc)4]. DFT (Density Functional Theory) calculations on the B3LYP def2-TZVP level of theory were carried out to assign the order of redox events in 6 showing that the spatial distance towards the most recent redox center, instead of the binding mode, is decisive.

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells.

Mixed-valence (MV) binuclear ferrocenyl compounds have long been studied as models for testing theories of electron transfer and in attempts to design molecular-scale electronic devices (e.g., molecular wires). In contrary to that, far less attention has been paid to MV binuclear ferrocenes as anticancer agents. Herein, we discuss the synthesis of six 1,2,3-triazole ferrocenyl compounds for combined (spectro)electrochemical, electron paramagnetic resonance (EPR), computational, and anticancer activity studies. Our synthetic approach was based on the copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction and enabled us to obtain in one step compounds bearing either one, two, or three ferrocenyl entities linked to the common 1,2,3-triazole core. Thus, two series of complexes were obtained, which pertain to derivatives of 3'-azido-3'-deoxythymidine (AZT) and 3-azidopropionylferrocene, respectively. Based on the experimental and theoretical data, the two mono-oxidized species corresponding to binuclear AZT and trinuclear 3-azidopropionylferrocene complexes have been categorized as class II mixed-valence according to the classification proposed by Robin and Day. Of importance is the observation that these two compounds are more active against human A549 and H1975 non-small-cell lung cancer cells than their congeners, which do not show MV characteristics. Moreover, the anticancer activity of MV species competes or surpasses, dependent on the cell line, the activity of reference anticancer drugs such as cisplatin, tamoxifen, and 5-fluorouracil. The most active from the entire series of compounds was the binuclear thymidine derivative with the lowest IC50 value of 5 ± 2 µM against lung H1975 cancer cells. The major mechanism of antiproliferative activity for the investigated MV compounds is based on reactive oxygen species generation in cancer cells. This hypothesis was substantiated by EPR spin-trapping experiments and the observation of decreased anticancer activity in the presence of N-acetyl cysteine (NAC) free-radical scavenger.

Ferrocenyl-Pyrenes, Ferrocenyl-9,10-Phenanthrenediones, and Ferrocenyl-9,10-Dimethoxyphenanthrenes: Charge-Transfer Studies and SWCNT Functionalization.

The synthesis of 1-Fc- (3), 1-Br-6-Fc- (5 a), 2-Br-7-Fc- (7 a), 1,6-Fc2 - (5 b), 2,7-Fc2 -pyrene (7 b), 3,6-Fc2 -9,10-phenanthrenedione (10), and 3,6-Fc2 -9,10-dimethoxyphenanthrene (12; Fc=Fe(η5 -C5 H4 )(η5 -C5 H5 )) is discussed. Of these compounds, 10 and 12 form 1D or 2D coordination polymers in the solid state. (Spectro)Electrochemical studies confirmed reversible Fc/Fc+ redox events between -130 and 160 mV. 1,6- and 2,7-Substitution in 5 a (E°'=-130 mV) and 7 a (E°'=50 mV) influences the redox potentials, whereas the ones of 5 b and 7 b (E°'=20 mV) are independent. Compounds 5 b, 7 b, 10, and 12 show single Fc oxidation processes with redox splittings between 70 and 100 mV. UV/Vis/NIR spectroelectrochemistry confirmed a weak electron transfer between FeII /FeIII in mixed-valent [5 b]+ and [12]+ . DFT calculations showed that 5 b non-covalently interacts with the single-walled carbon nanotube (SWCNT) sidewalls as proven by, for example, disentangling experiments. In addition, CV studies of the as-obtained dispersions confirmed exohedral attachment of 5 b at the SWCNTs.