Chances and challenges of long-distance electron transfer for cellular redox reactions.

Biological redox reactions often use a set-up in which final redox partners are localized in different compartments and electron transfer (ET) among them is mediated by redox-active molecules. In enzymes, these ET processes occur over nm distances, whereas multi-protein filaments bridge µm ranges. Electrons are transported over cm ranges in cable bacteria, which are formed by thousands of cells. In this review, we describe molecular mechanisms that explain how respiration in a compartmentalized set-up ensures redox homeostasis. We highlight mechanistic studies on ET through metal-free peptides and proteins demonstrating that long-distance ET is possible because amino acids Tyr, Trp, Phe, and Met can act as relay stations. This cuts one long ET into several short reaction steps. The chances and challenges of long-distance ET for cellular redox reactions are then discussed.

Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria.

BACKGROUND: Joint arthroplasty has improved the quality of life of patients worldwide, but infections of the prosthesis are frequent and cause significant morbidity. Antimicrobial coatings for implants promise to prevent these infections. METHODS: We have synthesized nanocapsules of titanium dioxide in amorphous or anatase form containing silver as antibacterial agent and tested their impact on bacterial growth. Furthermore, we explored the possible effect of the nanocapsules on the immune system. First, we studied their uptake into macrophages using a combination of electron microscopy and energy-dispersive spectroscopy. Second, we exposed immune cells to the nanocapsules and checked their activation state by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: Silver-containing titanium dioxide nanocapsules show strong antimicrobial activity against both E. coli and S. aureus and even against a multidrug-resistant strain of S. aureus. We could demonstrate the presence of the nanocapsules in macrophages, but, importantly, the nanocapsules did not affect cell viability and did not activate proinflammatory responses at doses up to 20 µg/mL. CONCLUSION: Our bactericidal silver-containing titanium dioxide nanocapsules fulfill important prerequisites for biomedical use and represent a promising material for the coating of artificial implants.

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.

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.

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.

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.

Formation of Silver Nanoparticles by Electron Transfer in Peptides and c-Cytochromes.

The reduction of Ag+ ions to Ag0 atoms is a highly endergonic reaction step, only the aggregation to Agn clusters leads to an exergonic process. These elementary chemical reactions play a decisive role if Ag nanoparticles (AgNPs) are generated by electron transfer (ET) reactions to Ag+ ions. We studied the formation of AgNPs in peptides by photoinduced ET, and in c-cytochromes by ET from their Fe2+ /hemes. Our earlier photoinduced experiments in peptides had demonstrated that histidine prevents AgNP formation. We have now observed that AgNPs can be easily synthesized with less-efficient Ag+ -binding amino acids, and the rate increases in the order lysine

Crystal structures of a copper(II) and the isotypic nickel(II) and palladium(II) complexes of the ligand (E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-ol.

In the copper(II) complex, bis-{(E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naph-thalen-2-olato}copper(II), [Cu(C16H8Br3N2O)2], (I), the metal cation is coord-inated by two N atoms and two O atoms from two bidentate (E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-olate ligands, forming a slightly distorted square-planar environment. In one of the ligands, the tri-bromo-benzene ring is inclined to the naphthalene ring system by 37.4 (5)°, creating a weak intra-molecular Cu⋯Br inter-action [3.134 (2) Å], while in the other ligand, the tri-bromo-benzene ring is inclined to the naphthalene ring system by 72.1 (6)°. In the isotypic nickel(II) and palladium(II) complexes, namely bis-{(E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-olato}nickel(II), [Ni(C16H8Br3N2O)2], (II), and bis-{(E)-1-[(2,4,6-tri-bromo-phen-yl)diazen-yl]naphthalen-2-olato}palladium(II), [Pd(C16H8Br3N2O)2], (III), respectively, the metal atoms are located on centres of inversion, hence the metal coordination spheres have perfect square-planar geometries. The tri-bromo-benzene rings are inclined to the naphthalene ring systems by 80.79 (18)° in (II) and by 80.8 (3)° in (III). In the crystal of (I), mol-ecules are linked by C-H⋯Br hydrogen bonds, forming chains along [010]. The chains are linked by C-H⋯π inter-actions, forming sheets parallel to (011). In the crystals of (II) and (III), mol-ecules are linked by C-H⋯π inter-actions, forming slabs parallel to (10-1). For the copper(II) complex (I), a region of disordered electron density was corrected for using the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The formula mass and unit-cell characteristics of the disordered solvent mol-ecules were not taken into account during refinement.

Synthesis of New Polyether Ether Ketone Derivatives with Silver Binding Site and Coordination Compounds of Their Monomers with Different Silver Salts.

Polyether ether ketone (PEEK) is a well-known polymer used for implants and devices, especially spinal ones. To overcome the biomaterial related infection risks, 4-4'-difluorobenzophenone, the famous PEEK monomer, was modified in order to introduce binding sites for silver ions, which are well known for their antimicrobial activity. The complexation of these new monomers with different silver salts was studied. Crystal structures of different intermediates were obtained with a linear coordination between two pyridine groups and the silver ions in all cases. The mechanical and thermal properties of different new polymers were characterized. The synthesized PEEKN5 polymers showed similar properties than the PEEK ones whereas the PEEKN7 polymers showed similar thermal properties but the mechanical properties are not as good as the ones of PEEK. To improve these properties, these polymers were complexed with silver nitrate in order to "cross-link" with silver ions. The presence of ionic silver in the polymer was then confirmed by thermogravimetric analysis (TGA) and X-ray powder diffraction (XRPD). Finally, a silver-based antimicrobial compound was successfully coated on the surface of PEEKN5.

Electron transfer in peptides: on the formation of silver nanoparticles.

Some microorganisms perform anaerobic mineral respiration by reducing metal ions to metal nanoparticles, using peptide aggregates as medium for electron transfer (ET). Such a reaction type is investigated here with model peptides and silver as the metal. Surprisingly, Ag(+) ions bound by peptides with histidine as the Ag(+)-binding amino acid and tyrosine as photoinducible electron donor cannot be reduced to Ag nanoparticles (AgNPs) under ET conditions because the peptide prevents the aggregation of Ag atoms to form AgNPs. Only in the presence of chloride ions, which generate AgCl microcrystals in the peptide matrix, does the synthesis of AgNPs occur. The reaction starts with the formation of 100 nm Ag@AgCl/peptide nanocomposites which are cleaved into 15 nm AgNPs. This defined transformation from large nanoparticles into small ones is in contrast to the usually observed Ostwald ripening processes and can be followed in detail by studying time-resolved UV/Vis spectra which exhibit an isosbestic point.

New antimicrobial and biocompatible implant coating with synergic silver-vancomycin conjugate action.

Materials foreign to the body are used ever more frequently, as increasing numbers of patients require implants. As a consequence, the numbers of implant-related infections have grown as well, and with increasing resistance. Treatments often fail; thus, new antibacterial coating strategies are being developed by scientists to avoid, or at least strongly reduce, bacterial adhesion to implant surfaces. In this study, we focused on producing a self-protective coating combining silver(I) ions and a vancomycin-derived molecule, intelligent pyridinate vancomycin (IPV), with a synergetic and effective action against bacteria. These Ag(I) -IPV conjugate-coated surfaces are well characterized and exhibit strong bactericidal activity in vitro against Staphylococci strains. Furthermore, the released quantities of both drugs from the coated surfaces do not affect their biocompatibility and soft tissue integration. These newly developed Ag(I) -IPV conjugate coatings thus represent a possible and efficient protection method against bacterial adhesion and biofilm formation during and after implant surgery.

Bioinorganic chemistry of silver: its interactions with amino acids and peptides.

Silver and its compounds have been used for centuries for e.g. water storage, burn wounds or as eye ointment. Almost forgotten after the discovery of antibiotics, silver chemistry has had a revival over the past years as a means to combat multi-resistant bacteria. Although the details of its mechanism of action are still unknown, silver seems to be efficient as it interacts with many biomolecular targets in a cell. In our group, we contribute to the elucidation of this mechanism of action by investigating the interactions of silver ions with amino acids and peptides as well as the formation of nanoparticles related to the mechanism of biomineralization of silver.

The influence of dipole moments on the mechanism of electron transfer through helical peptides.

The life time of aromatic radical cations is limited by reactions like ß-elimination, dimerization, and addition to the solvent. Here we show that the attachment of such a radical cation to the C-terminal end of an α-/3(10)-helical peptide further reduces its life time by two orders of magnitude. For PPII-helical peptides, such an effect is only observed if the peptide contains an adjacent electron donor like tyrosine, which enables electron transfer (ET) through the peptide. In order to explain the special role of α-/3(10)-helical peptides, it is assumed that the aromatic radical cation injects a positive charge into an adjacent amide group. This is in accord with quantum chemical calculations and electrochemical experiments in the literature showing a decrease in the amide redox potentials caused by the dipole moments of long α-/3(10)-helical peptides. Rate measurements are in accord with a mechanism for a multi-step ET through α-/3(10)-helical peptides that uses the amide groups or H-bonds as stepping stones.

Silver nanoparticle formation in different sizes induced by peptides identified within split-and-mix libraries.

Split-and-mix libraries are an excellent tool for the identification of peptides that induce the formation of Ag nanoparticles in the presence of either light or sodium ascorbate to reduce Ag(+) ions. Structurally diverse peptides were detected in colorimetric on-bead screenings that generate Ag nanoparticles of different sizes, as confirmed by SEM and X-ray powder diffraction studies.