Bernd Abel

The Hydrated Electron: A Seemingly Familiar Chemical and Biological Transient

Since the discovery of the hydrated electron in bulk water in 1962, the species has been the subject of intense research and speculation. For many decades even the basic features of the simplest of all chemical and biological transients and reactants--such as its structure, binding motifs, lifetimes, and binding energies--remained elusive. Recently, another milestone in the research of the hydrated electron was the determination of its vertical binding energy (VBE). Also a long-lived hydrated electron near the surface of liquid water has been discovered. The present Minireview discusses the implications and consequences of this and other new findings in addition to the emerging complex picture of a solvated electron in water.

Primary Steps of pH-Dependent Insulin Aggregation Kinetics are Governed by Conformational Flexibility

Insulin aggregation critically depends on pH. The underlying energetic and structural determinants are, however, unknown. Here, we measure the kinetics of the primary aggregation steps of the insulin monomer in vitro and relate it to its conformational flexibility. To assess these primary steps the monomer concentration was monitored by mass spectrometry at various pH values and aggregation products were imaged by atomic force microscopy. Lowering the pH from 3 to 1.6 markedly accelerated the observed aggregation kinetics. The influence of pH on the monomer structure and dynamics in solution was studied by molecular dynamics simulations, with the protonation states of the titrable groups obtained from electrostatic calculations. Reduced flexibility was observed for low pH values, mainly in the C terminus and in the helix of the B chain; these corresponded to an estimated entropy loss of 150 J mol−1 K−1. The striking correlation between entropy loss and pH value is consistent with the observed kinetic traces. In analogy to the well‐known Φ value analysis, this result allows the extraction of structural information about the rate determining transition state of the primary aggregation steps. In particular, we suggest that the residues in the helix of the B chain are involved in this transition state.

Role of Water Complexes in the Reaction of Propionaldehyde with OH Radicals

There has been considerable debate and speculation about the role of weakly bound complexes in radical-molecule reactions in the gas phase, especially in atmospheric chemistry. Among the significant number of potentially important molecular aggregates in chemical reactions, water complexes are of particular interest. Beyond the well-known energy transfer role of water in complex-forming reactions, it has been shown that water may also have a catalytic effect on the kinetics of radical-molecule reactions because of reduced reaction barrier heights for the complexes. Here we report studies of the reaction of OH radicals and propionaldehyde in the presence and absence of water vapor between 300 and 60 K in Laval nozzle expansions. Water accelerates the overall reaction at low temperatures but much less pronounced than for the reaction of OH with acetaldehyde reported recently. Quantum chemical calculations help us to understand this behavior, which can be rationalized in terms of the stability of intermediate reaction complexes and the effect of water aggregation on the barrier separating prereactive complexes and products.

Biocompatible Silicon Surfaces through Orthogonal Click Chemistries and a High Affinity Silicon Oxide Binding Peptide

Multifunctionality is gaining more and more importance in the field of improved biomaterials. Especially peptides feature a broad chemical variability and are versatile mediators between inorganic surfaces and living cells. Here, we synthesized a unique peptide that binds to SiO(2) with nM affinity. We equipped the peptide with the bioactive integrin binding c[RGDfK]-ligand and a fluorescent probe by stepwise Diels-Alder reaction with inverse electron demand and copper(I) catalyzed azide-alkyne cycloaddition. For the first time, we report the generation of a multifunctional peptide by combining these innovative coupling reactions. The resulting peptide displayed an outstanding binding to silicon oxide and induced a significant increase in cell spreading and cell viability of osteoblasts on the oxidized silicon surface.

The influence of the ΔK280 mutation and N- or C-terminal extensions on the structure, dynamics, and fibril morphology of the tau R2 repeat

Tau is a microtubule-associated protein and is involved in microtubule assembly and stabilization. It consists of four repeats that bind to the microtubule. The ΔK280 deletion mutation in the tau R2 repeat region is directly associated with the development of the frontotemporal dementia parkinsonism linked to chromosome 17 (FTDP-17). This deletion mutation is known to accelerate tau R2 repeat aggregation. However, the secondary and the tertiary structures of the self-assembled ΔK280 tau R2 repeat mutant aggregates are still controversial. Moreover, it is unclear whether extensions by one residue in the N- or the C-terminus of this mutant can influence the secondary or the tertiary structure. Herein, we combine solid-state NMR, atomic force microscopy, electron microscopy and all-atom explicit molecular dynamics simulations to investigate the effects of the deletion mutation and the N- and the C-terminal extension of this mutant on the structure. Our main findings show that the deletion mutation induces the formation of small aggregates, such as oligomers, and reduces the formation of fibrils. However, the extensions in the N- or the C-terminus revealed more fibril formation than small aggregates. Further, in the deletion mutation only one structure is preferred, while the N- and the C-terminal extensions strongly lead to polymorphic states. Finally, our broad and combined experimental and computational techniques provide direct structural information regarding ΔK280 tau R2 repeat mutant aggregates and their extensions in the N- and C-terminii by one residue.

Multifunctional Coating Improves Cell Adhesion on Titanium by using Cooperatively Acting Peptides.

Promotion of cell adhesion on biomaterials is crucial for the long-term success of a titanium implant. Herein a novel concept is highlighted combining very stable and affine titanium surface adhesive properties with specific cell binding moieties in one molecule. A peptide containing L-3,4-dihydroxyphenylalanine was synthesized and affinity to titanium was investigated. Modification with a cyclic RGD peptide and a heparin binding peptide (HBP) was realized by an efficient on-resin combination of Diels-Alder reaction with inverse electron demand and Cu(I) catalyzed azide-alkyne cycloaddition. The peptide was fluorescently labeled by thiol Michael addition. Conjugating the cyclic RGD and HBP in one peptide gave improved spreading, proliferation, viability, and the formation of well-developed actin cytoskeleton and focal contacts of osteoblast-like cells.

Gold-Induced Fibril Growth: The Mechanism of Surface-Facilitated Amyloid Aggregation

Abstract The question of how amyloid fibril formation is influenced by surfaces is crucial for a detailed understanding of the process in vivo. We applied a combination of kinetic experiments and molecular dynamics simulations to elucidate how (model) surfaces influence fibril formation of the amyloid‐forming sequences of prion protein SUP35 and human islet amyloid polypeptide. The kinetic data suggest that structural reorganization of the initial peptide corona around colloidal gold nanoparticles is the rate‐limiting step. The molecular dynamics simulations reveal that partial physisorption to the surface results in the formation of aligned monolayers, which stimulate the formation of parallel, critical oligomers. The general mechanism implies that the competition between the underlying peptide–peptide and peptide–surface interactions must strike a balance to accelerate fibril formation.

Efficiency enhancement of a dielectric barrier plasma discharge by dielectric barrier optimization

The characteristic feature of a dielectric barrier discharge (DBD) is the dielectric barrier placed between the electrodes. In the present work, the influence of the dielectric barrier to the properties of a DBD in air was investigated. Spectroscopic characterization of the DBD and electrical measurements were carried out. It was shown that the efficiency of a DBD can be considerably improved by optimizing the dielectric barrier. The dielectric material should possess an appropriate relative permittivity and thickness. For thin dielectric barriers, a high secondary emission coefficient becomes important. Additionally, the use of only one dielectric barrier is advantageous.

Chemical Modification of a Tetrapyrrole-Type Photosensitizer: Tuning Application and Photochemical Action beyond the Singlet Oxygen Channel

Reactive oxygen species (ROS) formed by light activated photosensitizers (PSs) are the hallmark of photodynamic therapy (PDT). It is generally accepted that commonly used PSs generate singlet oxygen ((1)O2) as the cell-toxic species via type II photosensitization. We explored here the consequences of chemical modification and the influence of the net charge of a cationic tetrahydroporphyrin derivative (THPTS) relative to the basic molecular structure on the red-shift of absorption, solubility, mechanistic features, and photochemical as well as cell-toxic activity. In order to shed light into the interplay between chemical modification driven intra- and intermolecular photochemistry, intermolecular interaction, and function, a number of different spectroscopic techniques were employed and our experimental studies were accompanied by quantum chemical calculations. Here we show that for THPTS neither (1)O2 nor other toxic ROS (superoxide and hydroxyl radicals) are produced directly in significant quantities in aqueous solution (although the formation of singlet oxygen is energetically feasible and as such observed in acetonitrile). Nevertheless, the chemically modified tetrapyrrole photosensitizer displays efficient cell toxicity after photoexcitation. The distribution and action of THPTS in rat bladder caricinoma AY27 cells measured with fluorescence lifetime imaging microscopy shows accumulation of the THPTS in lysosomes and efficient cell death after irradiation. We found evidence that THPTS in water works mainly via the type I mechanism involving the reduction rather than oxidation of the excited triplet state THPTS(T1) via efficient electron donors in the biosystem environment and subsequent electron transfer to produce ROS indirectly. These intriguing structure-activity relationships may indeed open new strategies and avenues in developing PSs and PDT in general.

Kinetic Studies of the Reduction of [Co(dmgH)2(py)(Cl)] Revisited: Mechanisms, Products, and Implications

We report on a mechanistic investigation regarding the reduction of [Co(III)(dmgH)2(py)(Cl)] (dmg = dimethylglyoxime) by several complementary techniques. The reduction of [Co(III)(dmgH)2(py)(Cl)] was initiated by either electrochemical, photochemical, or pulse radiolytical techniques, and the corresponding products were analyzed by ESI mass spectrometry. In addition, all of the rate constants for each step were determined. We have found solid experimental as well as theoretical evidence for the appearance of a dinuclear complex [Co(II)Co(III)(dmgH)4(py)2(H2O)2](+) to be the final product of reduction, implying the initially reduced form of [Co(III)(dmgH)2(py)(Cl)] undergoes a dimerization with the starting material in solution.