Damian Plażuk

A [3]Ferrocenophane Polyphenol Showing a Remarkable Antiproliferative Activity on Breast and Prostate Cancer Cell Lines

We have previously shown that modification of polyphenols with a ferrocenyl group can dramatically enhance their cytotoxicity. We now present two new [3]ferrocenophane compounds, one of which has an antiproliferative effect seven times stronger than the corresponding noncyclic species, with IC50 values of 90 and 94 nM on hormone-independent MDA-MB-231 breast and PC-3 prostate cancer cell lines, respectively. Solubility studies in water using methylated beta-cyclodextrin and electron transfer studies are also presented.

A series of unconjugated ferrocenyl phenols: prospects as anticancer agents.

We recently reported that a ferrocenyl diphenol butene derivative showed a very strong cytotoxic effect on both hormone‐dependent and ‐independent breast cancer cell lines. In order to obtain more information about the structure–activity relationship in the cytotoxicity of small ferrocene compounds, we have prepared a series of simple unconjugated ferrocenyl diphenol complexes (ortho,para; meta,para; para,para). These compounds retain a reasonable to good affinity for both estrogen receptor types, with higher values for the β form, and superior binding for the para,para diphenol complex (RBA=28 %). In vitro these complexes exhibit significant cytotoxic effects on hormone‐independent prostate (PC3) and breast cancer cell lines (MDA‐MB231), with IC50 values between 2.5 and 4.1 μM. This effect is more marked with PC3, the ortho,para diphenol complex proving the most effective. On the hormone‐dependent MCF7 breast cancer cell line, the observed effect seems to be the result of two components, one cytotoxic (antiproliferative), the other estrogenic (proliferative). Electrochemical studies show that the cytotoxic effect of the complexes correlates with the ease of oxidation of the ferrocene group. All these complexes are much less cytotoxic than the ferrocenyl diphenol butene derivative.

Half-Sandwich Ruthenium(II) Biotin Conjugates as Biological Vectors to Cancer Cells

Ruthenium(II)-arene complexes with biotin-containing ligands were prepared so that a novel drug delivery system based on tumor-specific vitamin-receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in cancer cell lines with various levels of major biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the ligands. In all cases, coordination of ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru(II) -biotin complexes to avidin was investigated and was lower than that of unmodified biotin. Hill coefficients in the range 2.012-2.851 suggest strong positive cooperation between the complexes and avidin. To estimate the likelihood of binding to the biotin receptor/transporter, docking studies with avidin and streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half-sandwich ruthenium(II)-biotin conjugates may act as biological vectors to cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the biotin moiety was observed.

Synthesis and biological activities of ferrocenyl derivatives of paclitaxel

A series of ferrocenyl taxoids were prepared by acylation of paclitaxel and docetaxel with ferrocenecarboxylic acid and 3-ferrocenoylpropionic acid in good yield. The prepared compounds showed high activities against multidrug-resistant colon adenocarcinoma cell lines.

Acylation of Ferrocene and a 1,1′‐Diphosphaferrocene with Acyl Trifluoroacetates in the Presence of Trifluoromethanesulfonic (Triflic) Acid or Some Metal Triflates

Abstract Ferrocene and 3,3′,4,4′‐tetramethyl‐1,1′‐diphosphaferrocene undergo efficient acylation by acyl trifluoroacetates (prepared in situ from carboxylic acids and trifluoroacetic anhydride) in the presence of an excess of trifluoromethanesulfonic acid or catalytic amounts (10% mol.) of its ytterbium or hafnium salts.

A new class of pyrenyl solid-state emitters: 1-pyrenyl ynones. Synthesis via the Friedel–Crafts route, molecular and electronic structure and photophysical properties

Friedel–Crafts acylation of pyrene with alkynoic acids in the presence of trifluoroacetic anhydride and triflic acid constitutes a direct and efficient route to 1-pyrenyl ynones. These compounds in chloroform solution emit fluorescence at longer wavelengths, with higher quantum yields and longer lifetimes than a typical saturated acylpyrene derivative, 1-acetylpyrene. Moreover, in contrast to 1-acetylpyrene, they are moderate solid-state emitters. Comparative DFT studies revealed strong stabilization of the LUMOs of 1-pyrenyl ynones in comparison to the LUMO of 1-acetylpyrene. The single-crystal X-ray structure of 1-(pyren-1-yl)but-2-yn-1-one showed π-interactions of pyrenyl moieties in the crystal lattice. Investigations of the solid-state fluorescence of this compound revealed emission from long-lived excited states, including excimer species.

Electronic and molecular structures and bulk second–order nonlinear optical properties of ferrocenyl ynones

Ferrocenyl ynones FcCOCCR (R = H, TMS, Ph) exhibit moderate second harmonic generation efficiencies in the solid state, whereas the methyl analog proved inactive. Their molecular structures and crystal packings were determined by single crystal X-ray diffraction, confirming that the inactive compound crystallizes in a centrosymmetric space group. The electronic structures of these compounds were studied experimentally (cyclic voltammetry, electronic absorption spectra) and theoretically (DFT and TD-DFT calculations). It appeared that the COCCR groups are stronger electron acceptors than the propionyl (COCH2CH3) group. Furthermore, these groups better stabilize metal-centred HOMO-2 to HOMO orbitals and lateral chain-centred LUMO orbitals and decrease HOMO-LUMO gaps. The TDDFT calculation of electronic transitions revealed that lower energy (LE) and higher energy (HE) bands observed in the electronic absorption spectra of compounds under study have more pronounced metal-to-ligand charge transfer character for ferrocenyl ynones than for propionylferrocene. The calculated static quadratic hyperpolarizabililities of ferrocenyl ynones are in the range ∼3 − 6 × 10−30 esu.

A Convenient Synthesis of Conjugated ω-Arylpolyenals via Wittig Reaction with (1,3-Dioxan-2-yl-methyl)triphenylphosphonium Bromide/Sodium Hydride

Abstract Commercially available reagent, (1,3-dioxan-2-yl-methyl)triphenylphosphonium bromide, sodium hydride and a catalytic amount of 18-crown-6 has proven efficient system for vinylic extension of ο-arylpolyenals.

Structural investigation of the interactions of biotinylruthenocene with avidin

The crystal structure of avidin, a protein from hen egg white, was determined in the form of a complex with biotinylruthenocene. This biotin-derived organometallic ligand is a potential anticancer agent for targeted therapy based upon avidin-biotin technology. Isothermal titration calorimetry experiments, involving avidin complexes with biotin (vitamin H or B7) derivatives, show differences in their affinity to the protein in comparison to its avidin-biotin complex, the strongest known biochemical interaction in Nature. The crystal structure of the first complex of avidin with biotinylruthenocene, determined at 2.5Å resolution (PDB: 4I60), shows unique interactions of the ruthenocene moiety with avidin. Biotin derivatives exhibit weaker affinity to avidin then biotin, which allows their wider use in biotechnology. The specific properties of biotinylruthenocene and the knowledge of its interactions with avidin may be useful in biochemical, medical, and nanotechnological applications.

Friedel-Crafts Reaction of Dimethyl 2-Oxopropylphosphonate and Diethyl 2,2-Diethoxyethylphosphonate With Electron-Rich Arenes

Dimethyl 2-oxopropylphosphonate and diethyl 2,2-diethoxyethylphosphonate react with electron-rich arenes such as phenol, anisole, 1,3-dimethoxybenzene, and 1-methylpyrrole in the presence of trifluoromethanesulfonic acid to afford β,β-diarylphosphonates in moderate to good yield. The minor products observed in some cases are β -aryl-α,β -unsaturated phosphonates.