Ferrocenyl‐Coupled N‐Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs

Four gold(I) carbene complexes featuring 4‐ferrocenyl‐substituted imidazol‐2‐ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug‐resistant ones, with low micromolar or nanomolar IC₅₀ (72 h) values, according to their lipophilicity and cellular uptake. The delocalized lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: through a genuine ferrocene effect and by inhibiting the thioredoxin reductase. Both complexes gave rise to a reorganization of the F‐actin cytoskeleton in endothelial and melanoma cells, associated with a G1 phase cell cycle arrest and a retarded cell migration. They proved antiangiogenic in tube formation assays with endothelial cells and vascular‐disruptive on real blood vessels in the chorioallantoic membrane of chicken eggs. Biscarbene complex 10 was also tolerated well by mice where it led to a volume reduction of xenograft tumors by up to 80 %.     

Bromine formation in solid NaBr/KNO<Subscript>3</Subscript> mixture and assay of this reaction via bromination of activated aromatics

Bromine formation in the mixture of solid NaBr and KNO₃ was observed and the process was studied in different acidified organic solvent–water mixtures by monitoring the bromination of acetanilide and other compounds, containing activated aromatic substituents. This assay is based on fast bromination reaction of these aromatic compounds, as differently from the assay of Br₂, the brominated aromatics can be easily determined by conventional gas chromatography–mass spectrometry (GC–MS) methods. It was found that bromine was generated autocatalytically on the surface of salt crystals and the reaction was characterized by a lag period, the duration of which depended on reaction conditions, and importantly on the type of the organic solvent in the reaction mixture. As the bromine formation could be easily controlled by reaction conditions, it was suggested that the studied reaction might have practical applications as an environmentally friendly and economically feasible bromination method. It was also shown that the bromination of aromatics followed the mechanism of classical electrophilic aromatic substitution reaction.     

Photoinduced redox reactions between colloidal manganese dioxide and some organic compounds of environmental importance

Numerous organic compounds of environmental importance, i.e., phenol, citric, tartaric, and oxalic acids, proved to promote or accelerate reductive dissolution of colloidal manganese dioxide upon irradiation. This is accounted for the formation of surface-located charge-transfer complexes between the MnO₂ particulates and the organic electron donors. From the dependences of the rate of the photoassisted and thermal dissolution on the concentration of the organic compounds, the equilibrium constants for the formation of these complexes have been determined in the case of phenol, resorcinol, citrate, and tartaric acid. The quantum yields for these photoinduced reactions (at λ _ir = 365 nm), however, do not show any correlation with the values of the corresponding equilibrium constants, although adsorption is prerequisite for the efficient reductive dissolution of MnO₂. The changes in pH markedly affect the rate of this process, indicating that protonation of both the electron donors and the surface of the MnO₂ particulates may play significant roles in these systems. The results of experiments carried out in manganese dioxide excess suggest that total mineralization of organic electron donors is strongly hindered by the disadvantageous adsorption properties of the primary redox products. Dedicated to Professor Janos H. Fendler on the occasion of his 70th birthday.     

Highly Conjugated Bis(benzo[b]phosphole)-P-oxides: Synthesis and Electrochemical,Optical, and Computational Studies

The first examples of a π-conjugated benzo[b]phosphole P-oxide in which two phosphole P-oxide units are connected by a carbon-carbon double bond are described. The molecules are synthesized as E isomers with respect to the carbon-carbon double bond and exist as stable cis and trans isomers (chiral and meso one respectively) relatively to the two stereogenic P atoms. The optical and electrochemical properties of both isomers have been investigated by experiment and computations.     

The Prenucleation Equilibrium of the Parathyroid Hormone Determines the Critical Aggregation Concentration and Amyloid Fibril Nucleation

Nucleation and growth of amyloid fibrils were found to only occur in supersaturated solutions above a critical concentration (c_crit). The biophysical meaning of c_crit remained mostly obscure, since typical low values of c_crit in the sub-μM range hamper investigations of potential oligomeric states and their structure. Here, we investigate the parathyroid hormone PTH₈₄ as an example of a functional amyloid fibril forming peptide with a comparably high c_crit of 67±21 μM. We describe a complex concentration dependent prenucleation ensemble of oligomers of different sizes and secondary structure compositions and highlight the occurrence of a trimer and tetramer at c_crit as possible precursors for primary fibril nucleation. Furthermore, the soluble state found in equilibrium with fibrils adopts to the prenucleation state present at c_crit. Our study sheds light onto early events of amyloid formation directly related to the critical concentration and underlines oligomer formation as a key feature of fibril nucleation. Our results contribute to a deeper understanding of the determinants of supersaturated peptide solutions. In the current study we present a biophysical approach to investigate c_crit of amyloid fibril formation of PTH₈₄ in terms of secondary structure, cluster size and residue resolved intermolecular interactions during oligomer formation. Throughout the investigated range of concentrations (1 μM to 500 μM) we found different states of oligomerization with varying ability to contribute to primary fibril nucleation and with a concentration dependent equilibrium. In this context, we identified the previously described c_crit of PTH₈₄ to mark a minimum concentration for the formation of homo-trimers/tetramers. These investigations allowed us to characterize molecular interactions of various oligomeric states that are further converted into elongation competent fibril nuclei during the lag phase of a functional amyloid forming peptide.     

Multifunctional Antioxidants: Regenerable Radical‐Trapping and Hydroperoxide‐Decomposing Ebselenols

Regenerable, multifunctional ebselenol antioxidants were prepared that could quench peroxyl radicals more efficiently than α‐tocopherol. These compounds act as better mimics of the glutathione peroxidase enzymes than ebselen. Production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human mononuclear cells was considerably decreased upon exposure to the organoselenium compounds. At a concentration of 25 μm , the ebselenol derivatives showed minimal toxicity in pre‐osteoblast MC3T3 cells.     

Luminescent sensing of organophosphates using europium(III) containing imprinted polymers prepared by RAFT polymerization

Molecularly imprinted polymers capable of sensing organophosphorous compounds by luminescence have been prepared by reversible addition fragmentation chain transfer (RAFT) polymerization. The polymer contained a dithiobenzoate substituted tris(β-diketonate) europium(III) complex which served as a polymerization substrate and as a luminescent binding site for pinacolyl methylphosphonate (PMP), the hydrolysis product of the nerve agent Soman. The resultant polymer allowed quantitation of PMP in the low ppb range with minimal interference from similar compounds. Polymers were characterized by luminescence spectroscopy and scanning electron microscopy.     

Ga-NMR study of the low-energy excitations in

We report the results of ⁶⁹Ga- and ⁷¹Ga-NMR measurements on NdGa₂ at temperatures between 0.1 and and in applied magnetic fields between zero and 74 kOe. NdGa₂ orders antiferromagnetically below and undergoes several metamagnetic transitions in external magnetic fields. In zero applied magnetic field and below the temperature dependence of the spin-lattice relaxation rate T1 ^-1 ( T ) shows a large linear-in-T term, about two orders of magnitude higher than for the reference compound LaGa₂. This strong enhancement confirms the presence of low-energy excitations in the antiferromagnetic phase of NdGa₂ as was previously indicated by specific heat data. Above , T1 ^-1 ( T ) is dominated by an exponential term, which we associate with excitations between the lowest energy levels of the f-electron system. The separation of these energy levels is determined by exchange, crystal-field and Zeeman interactions. Received 3 September 1998 and Received in final form 3 November 1998