4-[(E)-2-(1-Pyrenyl)Vinyl]Pyridine Complexes: How to Modulate the Toxicity of Heavy Metal Ions to Target Microbial Infections.

Pyrene derivatives are regularly proposed for use in biochemistry as dyes due to their photochemical characteristics. Their antibacterial properties are, however, much less well understood. New complexes based on 4-[(E)-2-(1-pyrenyl)vinyl]pyridine (PyPe) have been synthesized with metal ions that are known to possess antimicrobial properties, such as zinc(II), cadmium(II), and mercury(II). The metal ion salts, free ligand, combinations thereof, and the coordination compounds themselves were tested for their antibacterial properties through microdilution assays. We found that the ligand is able to modulate the antibacterial properties of transition metal ions, depending on the complex stability, the distance between the ligand and the metal ions, and the metal ions themselves. The coordination by the ligand weakened the antibacterial properties of heavy metal ions (Cd(II), Hg(II), Bi(III)), allowing the bacteria to survive higher concentrations thereof. Mixing the ligand and the metal ion salts without forming the complex beforehand enhanced the antibacterial properties of the cations. Being non-cytotoxic itself, the ligand therefore balances the biological consequences of heavy metal ions between toxicity and therapeutic weapons, depending on its use as a coordinating ligand or simple adjuvant.

A Rapid, Highly Sensitive and Selective Phosgene Sensor Based on 5,6-Pinenepyridine.

The toxicity of phosgene (COCl2 ) combined with its extensive use as a reactant and building block in the chemical industry make its fast and accurate detection a prerequisite. We have developed a carboxylic derivative of 5,6-pinenepyridine which is able to act as colorimetric and fluorimetric sensor for phosgene in air and solution. For the first time, the formation of a pyrido-[2,1-a]isoindolone was used for this purpose. In solution, the sensing reaction is extremely fast (under 5 s), selective and highly sensitive, with a limit of detection (LOD) of 9.7 nM/0.8 ppb. When fixed on a solid support, the sensor is able to detect the presence of gaseous phosgene down to concentrations of 0.1 ppm, one of the lowest values reported to date.

Efficient synthesis of isoindolones by intramolecular cyclisation of pyridinylbenzoic acids.

A straightforward one-pot method for the synthesis of unreported pyrido-[2,1-a]isoindolones in excellent yield is described. Two novel isoindolones were synthesized and fully characterized. The alkyl substituents on the pyridine play an important role in the outcome of the reaction. The mechanism, investigated through DFT calculations, features an unprecendented intramolecular cyclization reaction involving a carboxylic acid activated by tosyl chloride and an electron-poor pyridinic nitrogen. This protocol completes the known strategies to obtain functionalized isoindolones.

General Chemistry: Large Classes, Mixed Public, Three Languages (A Personal Experience).

At most universities, teaching general chemistry to fresh(wo)men is a challenge as the audience is usually composed of students of different backgrounds and interests. On one hand, the lecture is meant to bring all students to a basic level of chemistry required for future studies, on the other hand, certain concepts are discussed in much more depth than what students know from school. While it is already a balancing act to teach the content to students with little chemistry knowledge without boring those who took intensive classes at school, the University of Fribourg adds a challenge by teaching officially bilingual classes.

Handling (Nano)Silver as Antimicrobial Agent: Therapeutic Window, Dissolution Dynamics, Detection Methods and Molecular Interactions.

Silver is an antimicrobial agent well known since antiquity. With the emergence of multiresistant bacteria, it has come back into the focus of research, and ionic as well as nano-sized silver have been studied in vitro and in vivo. The results are controversial, silver being discussed as the "silver bullet" or a "wolf in sheep's clothing". A thorough search of literature from chemistry, materials and environmental science, biology and medicine led to this Review which summarizes the potential use of silver and its compounds in medicine, ongoing processes of dissolution and the different methods by which this usefulness can be evaluated. It also highlights the therapeutic window of silver, mechanistic interactions of silver and biological media as well as best practices for handling silver in a biomedical environment. This Review reflects the current knowhow and observations, and may thus give hints and guidelines to understand and interpret the observed effects.

Tautomerism and Self-Association in the Solution of New Pinene-Bipyridine and Pinene-Phenanthroline Derivatives.

Two novel pinene-type ligands have been synthesized and their tautomeric and self-associating behavior studied in solution and in the solid state. The first ligand, an acetylated derivative of 5,6-pinene-bipyridine, displays keto-enol tautomerism in solution. This tautomeric equilibrium was studied by NMR and UV-Vis spectroscopy in various solvents, and the results were compared with the ones obtained through DFT calculations. The second ligand was obtained by an unusual oxidation of the phenanthroline unit of a pinene-phenanthroline derivative. This compound exists as a single tautomer in solution and aggregates both in solution (as observed by NMR) and in the solid state through H-bonding as observed by X-ray structure determination and confirmed by DFT studies.

Kinetics and Mechanism of Mineral Respiration: How Iron Hemes Synchronize Electron Transfer Rates.

Anaerobic microorganisms of the Geobacter genus are effective electron sources for the synthesis of nanoparticles, for bioremediation of polluted water, and for the production of electricity in fuel cells. In multistep reactions, electrons are transferred via iron/heme cofactors of c-type cytochromes from the inner cell membrane to extracellular metal ions, which are bound to outer membrane cytochromes. We measured electron production and electron flux rates to 5×105  e s-1 per G. sulfurreducens. Remarkably, these rates are independent of the oxidants, and follow zero order kinetics. It turned out that the microorganisms regulate electron flux rates by increasing their Fe2+ /Fe3+ ratios in the multiheme cytochromes whenever the activity of the extracellular metal oxidants is diminished. By this mechanism the respiration remains constant even when oxidizing conditions are changing. This homeostasis is a vital condition for living systems, and makes G. sulfurreducens a versatile electron source.

Anion-Induced Structural Diversity of Zn and Cd Coordination Polymers Based on Bis-9,10-(pyridine-4-yl)-anthracene, Their Luminescent Properties, and Highly Efficient Sensing of Nitro Derivatives and Herbicides.

Luminescent coordination polymers (CPs) of Zn2+ or Cd2+ and bis-9,10-(pyridine-4-yl)-anthracene (BA) show different 1D and 2D topologies depending on the anion used in the precursor. Compounds {[Zn(µ2-BA)(MeOH)2(p-Tos)2]} n (1) and {[Zn(µ2-BA)(MeOH)2(CF3CO2)2]} n (2) form linear structures and {BA@[Zn(µ2-BA)(MeOH)2(H2O)2](CF3SO3)2} n (3) featuring intercalation of uncoordinated BA molecules into linear ribbons. Cd-based CPs {[Cd(µ2-BA)2(ClO4)2]· n(DCM)} n (4) and {[Cd(µ2-BA)(MeOH)2(Dioxane)(η2-SiF6)]·mDioxane} n (5) form porous structures with 2D lattices. All complexes exhibit strong blue emission in the solid state with average lifetimes between 8 and 13 ns. The emission of compound 4 is sensitive to the presence of nitro aromatics, simazine, and trichloroanisole (TCA) and demonstrates nonlinear Stern-Volmer quenching kinetics. Limits of detection (LOD) of 15 and 16 ppb for picric acid and TCA were achieved, respectively.

Sequential Multiple-Target Sensor: In3+, Fe2+, and Fe3+ Discrimination by an Anthracene-Based Probe.

Indium is a nonphysiological toxic metal widely used in industry. While misunderstood, its toxicity is proposed to be linked to a perturbation of Fe3+ homeostasis through the binding of In3+ ions to essential iron metalloproteins such as transferrins. Therefore, the monitoring of In3+ and Fe3+ in biological environments is of prime interest for both basic research and diagnosis. Here we report the design of a salen-type anthracene-based probe able to selectively sense and discriminate In3+ and Fe2+/3+ ions by fluoro-colorimetry.

Surface Modifications of Positive-Electrode Materials for Lithium Ion Batteries.

Lithium ion batteries are typically based on one of three positive-electrode materials, namely layered oxides, olivine- and spinel-type materials. The structure of any of them is 'resistant' to electrochemical cycling, and thus, often requires modification/post-treatment to improve a certain property, for example, structural stability, ionic and/or electronic conductivity. This review provides an overview of different examples of coatings and surface modifications used for the positive-electrode materials as well as various characterization techniques often chosen to confirm/detect the introduced changes. It also assesses the electrochemical success of the surface-modified positive-electrode materials, thereby highlighting remaining challenges and pitfalls.

Synthesis and Applications of Nanocontainers and Nanorattles.

Nanorattles and hollow nanocontainers have unique properties related to the presence of a void space inside the shell, which has been shown to improve the properties of materials for e.g. catalysis, drug release, sensor materials or lithium ion batteries. This article summarizes our recent progress in the synthesis of hollow silica, titania and ceria nanorattles and nanocontainers, eventually encapsulating AgNPs as cargo and highlights their potential applications in catalysis and biomedicine.

Functional Polymers Through Mechanochemistry.

While coupling mechanical and chemical processes is widespread in living organisms, the idea to harness the mechanically induced dissociation of weak covalent and non-covalent bonds to create artificial materials that respond to mechanical stimulation has only recently gained attention. Here we summarize our activities that mainly revolve around the exploitation of non-covalent interactions in (supramolecular) polymeric materials with the goal to translate mechanical stresses into useful, pre-defined events. Focusing on mechano- chromic polymers that alter their optical absorption or fluorescence properties, several new operating principles, mechanosensitive entities, and materials systems were developed. Such materials are expected to be useful for technical applications that range from the detection of very small forces in biological systems to the monitoring of degradation processes and damage in coatings and structural objects.

Tautomerism as primary signaling mechanism in metal sensing: the case of amide group.

The concept for sensing systems using the tautomerism as elementary signaling process has been further developed by synthesizing a ligand containing 4-(phenyldiazenyl)naphthalene-1-ol as a tautomeric block and an amide group as metal capturing antenna. Although it has been expected that the intramolecular hydrogen bonding (between the tautomeric hydroxy group and the nitrogen atom from the amide group) could stabilize the pure enol form in some solvents, the keto tautomer is also observed. This is a result from the formation of intramolecular associates in some solvents. Strong bathochromic and hyperchromic effects in the visible spectra accompany the 1:1 formation of complexes with some alkaline earth metal ions.

Amide Neighbouring-Group Effects in Peptides: Phenylalanine as Relay Amino Acid in Long-Distance Electron Transfer.

In nature, proteins serve as media for long-distance electron transfer (ET) to carry out redox reactions in distant compartments. This ET occurs either by a single-step superexchange or through a multi-step charge hopping process, which uses side chains of amino acids as stepping stones. In this study we demonstrate that Phe can act as a relay amino acid for long-distance electron hole transfer through peptides. The considerably increased susceptibility of the aromatic ring to oxidation is caused by the lone pairs of neighbouring amide carbonyl groups, which stabilise the Phe radical cation. This neighbouring-amide-group effect helps improve understanding of the mechanism of extracellular electron transfer through conductive protein filaments (pili) of anaerobic bacteria during mineral respiration.

WRINKLED1 and ACYL-COA:DIACYLGLYCEROL ACYLTRANSFERASE1 regulate tocochromanol metabolism in Arabidopsis.

Photosynthetic organisms such as plants, algae and some cyanobacteria synthesize tocochromanols, a group of compounds that encompasses tocopherols and tocotrienols and that exhibits vitamin E activity in animals. While most vitamin E biosynthetic genes have been identified in plant genomes, regulatory genes controlling tocopherol accumulation are currently unknown. We isolated by forward genetics Arabidopsis enhanced vitamin E (eve) mutants that overaccumulate the classic tocopherols and plastochromanol-8, and a tocochromanol unknown in this species. We mapped eve1 and eve4, and identified the unknown Arabidopsis tocochromanol by using a combination of analytical tools. In addition, we determined its biosynthetic pathway with a series of tocochromanol biosynthetic mutants and transgenic lines. eve1 and eve4 are two seed lipid mutants affecting the WRINKLED1 (WRI1) and ACYL-COA:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) genes, respectively. The unknown tocochromanol is 11'-12' γ-tocomonoenol, whose biosynthesis is VITAMIN E 1 (VTE1) - and VTE2-dependent and is initiated by the condensation of homogentisate (HGA) and tetrahydrogeranylgeranyl pyrophosphate. This study identifies the first two regulatory genes, WRI1 and DGAT1, that control the synthesis of all tocochromanol forms in seeds, and shows the existence of a metabolic trade-off between lipid and tocochromanol metabolisms. Moreover, it shows that Arabidopsis possesses a tocomonoenol biosynthetic pathway that competes with tocopherol synthesis.

Ag Nanoencapsulation for Antimicrobial Applications.

Biomaterial-related infections remain a significant challenge in medicine. Antimicrobial materials on the basis of Ag nanoparticles represent a promising solution for this issue. Therefore several Ag-containing nanocontainers and nanorattles have been synthesized and characterized that exhibit remarkable control over the release of Ag+ as antimicrobial active species. Their biological evaluation against prokaryotic as well as eukaryotic cells reveals that they fulfill the prerequisites for applications as antimicrobial implant coatings.

Triggered Metal Ion Release and Oxidation: Ferrocene as a Mechanophore in Polymers.

The introduction of mechanophores into polymers makes it possible to transduce mechanical forces into chemical reactions that can be used to impart functions such as self-healing, catalytic activity, and mechanochromic response. Here, an example of mechanically induced metal ion release from a polymer is reported. Ferrocene (Fc) was incorporated as an iron ion releasing mechanophore into poly(methyl acrylate)s (PMAs) and polyurethanes (PUs). Sonication triggered the preferential cleavage of the polymers at the Fc units over other bonds, as shown by a kinetic study of the molar mass distribution of the cleaved Fc-containing and Fc-free reference polymers. The released and oxidized iron ions can be detected with KSCN to generate the red-colored [Fe(SCN)n (H2 O)6-n )](3-n)+ complex or reacted with K4 [Fe(CN)6 ] to afford Prussian blue.

Heptacoordinate CoII Complex: A New Architecture for Photochemical Hydrogen Production.

The first heptacoordinate cobalt catalyst for light-driven hydrogen production in water has been synthesized and characterized. Photochemical experiments using [Ru(bpy)3 ]2+ as photosensitizer gave a turnover number (TON) of 16300 mol H2 (mol cat.)-1 achieved in 2 hours of irradiation with visible (475 nm) light. This promising result provides a path forward in the development of new structures to improve the efficiency of the catalysis.

Characteristics and properties of nano-LiCoO2 synthesized by pre-organized single source precursors: Li-ion diffusivity, electrochemistry and biological assessment.

BACKGROUND: LiCoO2 is one of the most used cathode materials in Li-ion batteries. Its conventional synthesis requires high temperature (>800 °C) and long heating time (>24 h) to obtain the micronscale rhombohedral layered high-temperature phase of LiCoO2 (HT-LCO). Nanoscale HT-LCO is of interest to improve the battery performance as the lithium (Li+) ion pathway is expected to be shorter in nanoparticles as compared to micron sized ones. Since batteries typically get recycled, the exposure to nanoparticles during this process needs to be evaluated. RESULTS: Several new single source precursors containing lithium (Li+) and cobalt (Co2+) ions, based on alkoxides and aryloxides have been structurally characterized and were thermally transformed into nanoscale HT-LCO at 450 °C within few hours. The size of the nanoparticles depends on the precursor, determining the electrochemical performance. The Li-ion diffusion coefficients of our LiCoO2 nanoparticles improved at least by a factor of 10 compared to commercial one, while showing good reversibility upon charging and discharging. The hazard of occupational exposure to nanoparticles during battery recycling was investigated with an in vitro multicellular lung model. CONCLUSIONS: Our heterobimetallic single source precursors allow to dramatically reduce the production temperature and time for HT-LCO. The obtained nanoparticles of LiCoO2 have faster kinetics for Li+ insertion/extraction compared to microparticles. Overall, nano-sized LiCoO2 particles indicate a lower cytotoxic and (pro-)inflammogenic potential in vitro compared to their micron-sized counterparts. However, nanoparticles aggregate in air and behave partially like microparticles.

Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells.

The progression in the use of orthopedic implants has led to an increase in the absolute number of implant infections, triggering a search for more effective antibacterial coatings. Nanorattles have recently gained interest in biomedical applications such as drug delivery, as encapsulation of the cargo inside the hollow structure provides a physical protection from the surrounding environment. Here, silver-containing silica nanorattles (Ag@SiO2) were evaluated for their antimicrobial potential and for their impact on cells of the immune system. We show that Ag@SiO2 nanorattles exhibited a clear antibacterial effect against Escherichia coli as well as Staphylococcus aureus found in post-operative infections. Immunotoxicological analyses showed that the particles were taken up through an active phagocytic process by dendritic cells of the immune system and did not affect their viability nor induce unwanted immunological effects. Silver-containing silica nanorattles thus fulfill several prerequisites for an antibacterial coating on surgical implants.