The small molecule activator S3969 stimulates the epithelial sodium channel by interacting with a specific binding pocket in the channel's β-subunit.

The epithelial sodium channel (ENaC) is essential for mediating sodium absorption in several epithelia. Its impaired function leads to severe disorders, including pseudohypoaldosteronism type 1 and respiratory distress. Therefore, pharmacological ENaC activators have potential therapeutic implications.

Efficient Assessment of 'Instantaneous pK' Values from Molecular Dynamics Simulations.

We present a molecular simulation approach to studying the role of local and momentary molecular environment for potential acid-base reactions. For this, we combine thermodynamic considerations on the pK of ionic species with rapid sampling of energy changes related to (de)protonation. Using dispersed carbonate ions in water as a reference, our approach aims at the fast assessment of the momentary protonation energy, and thus the 'instantaneous pK', of calcium-carbonate ion aggregates.

Small-Molecular-Weight Additives Modulate Calcification by Interacting with Prenucleation Clusters on the Molecular Level.

Small-molecular-weight (MW) additives can strongly impact amorphous calcium carbonate (ACC), playing an elusive role in biogenic, geologic, and industrial calcification. Here, we present molecular mechanisms by which these additives regulate stability and composition of both CaCO solutions and solid ACC. Potent antiscalants inhibit ACC precipitation by interacting with prenucleation clusters (PNCs); they specifically trigger and integrate into PNCs or feed PNC growth actively.

Directed Dehydration as Synthetic Tool for Generation of a New Na SnS Polymorph: Crystal Structure, Na Conductivity, and Influence of Sb-Substitution.

We present the convenient synthesis and characterization of the new ternary thiostannate Na SnS (space group ) by directed removal of crystal water molecules from Na SnS ⋅14 H O. The compound represents a new kinetically stable polymorph of Na SnS , which is transformed into the known, thermodynamically stable form (space group ) at elevated temperatures. Thermal co-decomposition of mixtures with Na SbS ⋅9 H O generates solid solution products Na Sn Sb S (x=0.

The nano- and meso-scale structure of amorphous calcium carbonate.

Understanding the underlying processes of biomineralization is crucial to a range of disciplines allowing us to quantify the effects of climate change on marine organisms, decipher the details of paleoclimate records and advance the development of biomimetic materials. Many biological minerals form via intermediate amorphous phases, which are hard to characterize due to their transient nature and a lack of long-range order. Here, using Monte Carlo simulations constrained by X-ray and neutron scattering data together with model building, we demonstrate a method for determining the structure of these intermediates with a study of amorphous calcium carbonate (ACC) which is a precursor in the bio-formation of crystalline calcium carbonates.

Hydration breaking and chemical ordering in a levitated NaCl solution droplet beyond the metastable zone width limit: evidence for the early stage of two-step nucleation.

For over two decades, NaCl nucleation from a supersaturated aqueous solution has been predicted to occur a two-step nucleation (TSN) mechanism, , two sequential events, the formation of locally dense liquid regions followed by structural ordering. However, the formation of dense liquid regions in the very early stage of TSN has never been experimentally observed. By using a state-of-the-art technique, a combination of electrostatic levitation (ESL) and synchrotron X-ray and Raman scatterings, we find experimental evidence that indicates the formation of dense liquid regions in NaCl bulk solution at an unprecedentedly high level of supersaturation ( = 2.

Interface between Water-Solvent Mixtures and a Hydrophobic Surface.

The mechanism behind the stability of organic nanoparticles prepared by liquid antisolvent (LAS) precipitation without a specific stabilizing agent is poorly understood. In this work, we propose that the organic solvent used in the LAS process rapidly forms a molecular stabilizing layer at the interface of the nanoparticles with the aqueous dispersion medium. To confirm this hypothesis, -octadecyltrichlorosilane (OTS)-functionalized silicon wafers in contact with water-solvent mixtures were used as a flat model system mimicking the solid-liquid interface of the organic nanoparticles.

Red light-triggered photoreduction on a nucleic acid template.

Conjugate Sn(iv)(pyropheophorbide a)dichloride-(peptide nucleic acid) catalyzes reduction of azobenzene derivatives in the presence of complementary nucleic acid (NA) upon irridiation with red light (660 nm). This is the first red light-induced NA-templated photoreduction. It is highly sensitive to single mismatches in the NA-template and can detect down to 5 nM NAs.

Size-Dependent Local Ordering in Melanin Aggregates and Its Implication on Optical Properties.

We present atomic scale models of differently sized eumelanin nanoaggregates from molecular dynamics simulations combined with a simulated annealing procedure. The analysis reveals the formation of secondary structures due to π-stacking on one hand, but on the other hand a broad distribution of stack geometries in terms of stack size, horizontal displacement angles, and relative torsion angles. The displacement angle distribution, which is a measure of the occurrence of zigzag and linear stacking motives, respectively, strongly depends on the aggregate size-and is hence controlled by the interplay of surface and bulk energy terms.

Molecular mechanisms of mesoporous silica formation from colloid solution: Ripening-reactions arrest hollow network structures.

The agglomeration of silica nanoparticles in aqueous solution is investigated from molecular simulations. Mimicking destabilization of colloidal solutions by full removal of protective moieties or surface charge, association of SiO2/Si(OH)4 core/shell particles leads to rapid proton transfer reactions that account for local silanole → silica ripening reactions. Yet, such virtually barrier-less binding is only observed within a limited contact zone.

Multi-Scale Modelling of Deformation and Fracture in a Biomimetic Apatite-Protein Composite: Molecular-Scale Processes Lead to Resilience at the μm-Scale.

Fracture mechanisms of an enamel-like hydroxyapatite-collagen composite model are elaborated by means of molecular and coarse-grained dynamics simulation. Using fully atomistic models, we uncover molecular-scale plastic deformation and fracture processes initiated at the organic-inorganic interface. Furthermore, coarse-grained models are developed to investigate fracture patterns at the μm-scale.

Atomistic modeling of a KRT35/KRT85 keratin dimer: folding in aqueous solution and unfolding under tensile load.

We present an atomistic model of a full KRT35/KRT85 dimer, a fundamental building block of human hair. For both monomers initial structures were generated using empirical tools based on homology considerations, followed by the formulation of a naiïve dimer model from docking the monomers in vacuum. Relaxation in aqueous solution was then explored from molecular dynamics simulation.

Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics.

Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization) and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle.

Mimicking the growth of a pathologic biomineral: shape development and structures of calcium oxalate dihydrate in the presence of polyacrylic acid.

The morphogenesis of calcium oxalate hydrates in aqueous solutions was investigated by varying the pH, oxalate concentration, and the concentration of the sodium salt of polyacrylate (PAA). With increasing amounts of PAA in solution, the shape of tetragonal calcium oxalate dihydrate (COD) changes from bipyramidal through elongated bipyramidal prisms to dumbbells and finally reverts to rodlike tetragonal bipyramidal prisms. PAA is incorporated into the prismatic zones of the growing COD crystals, thereby reducing the growth rate of the {100} faces along the <100> direction.

Molecular mechanics modeling of azobenzene-based photoswitches.

We present an extension of the generalized amber force field to allow the modeling of azobenzenes by means of classical molecular mechanics. TD-DFT calculations were employed to derive different interaction models for 4-hydroxy-4'-methyl-azobenzene, including the ground (S(0)) and S(1) excited state. For both states, partial charges and the -N = N- torsion potentials were characterized.

Atomistic modeling of apatite-collagen composites from molecular dynamics simulations extended to hyperspace.

The preparation of atomistic models of apatite-collagen composite mimicking enamel at length scales in the range of 1-10 nanometers is outlined. This bio-composite is characterized by a peculiar interplay of the collagen triplehelix and the apatite crystal structure. Structural coherence is however only obtained after drastic rearrangements, namely the depletion of protein-protein hydrogen bonds and the incorporation of calcium triangles which are stabilized by salt-bridges with the collagen molecule.

Motif reconstruction in clusters and layers: benchmarks for the Kawska-Zahn approach to model crystal formation.

A recently developed atomistic simulation scheme for investigating ion aggregation from solution is transferred to the morphogenesis of metal clusters grown from the vapor and layers deposited on a substrate surface. Both systems are chosen as benchmark models for intense motif reorganization during aggregate/layer growth. The applied simulation method does not necessarily involve global energy minimization after each growth event, but instead describes crystal growth as a series of structurally related configurations which may also include local energy minima.

Atomistic mechanisms of ZnO aggregation from ethanolic solution: ion association, proton transfer, and self-organization.

We report on atomistic simulations related to the nucleation of zinc oxide nanocrystals from ethanolic solution. The underlying mechanisms are explored from the very initial stage of Zn2+ and OH(-) ion association to the formation of nanometer-sized aggregates counting up to 250 ions. The embryonic aggregates consist of zinc and hydroxide ions, only.