Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria.

Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections.

The Earth's Lithosphere Inspires Materials Design.

Structural patterns found in living organisms have long been inspiring biomimetic materials design. Here, it is suggested that a rich palette of patterns occurring in inanimate Nature, and especially in the Earth's lithosphere, could be not less inspirational for design of novel architectured materials. This materials design paradigm is referred to as lithomimetics and it is demonstrated that some of the patterns found in the lithosphere can be emulated by established processes of severe plastic deformation.

A multiscale coarse-grained model to predict the molecular architecture and drug transport properties of modified chitosan hydrogels.

Hydrogels constructed with functionalized polysaccharides are of interest in a multitude of applications, chiefly the design of therapeutic and regenerative formulations. Tailoring the chemical modification of polysaccharide-based hydrogels to achieve specific drug release properties involves the optimization of many tunable parameters, including (i) the type, degree (χ), and pattern of the functional groups, (ii) the water-polymer ratio, and (iii) the drug payload. To guide the design of modified polysaccharide hydrogels for drug release, we have developed a computational toolbox that predicts the structure and physicochemical properties of acylated chitosan chains, and their impact on the transport of drug molecules.

Not-So-Innocent Anions Determine the Mechanism of Cationic Alkylators.

Alkylating reagents based on thioimidazolium ionic liquids were synthesized and the influence of the anion on the alkylation reaction mechanism explored in detail using both experimental and computational methods. Thioimidazolium cations transfer alkyl substituents to nucleophiles, however the reaction rate was highly dependent on anion identity, demonstrating that the anion is not innocent in the mechanism. Detailed analysis of the computationally-derived potential energy surfaces associated with possible mechanisms indicated that this dependence arises from a combination of anion induced electronic, steric and coordinating effects, with highly nucleophilic anions catalyzing a 2-step process while highly non-nucleophilic, delocalized anions favor a 1-step reaction.

Quantifying how step-wise fluorination tunes local solute hydrophobicity, hydration shell thermodynamics and the quantum mechanical contributions of solute-water interactions.

The ability to locally tune solute-water interactions and thus control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology. To date, the connection between (i) the hydrophobicity of a functional group; (ii) the local structure and thermodynamics of its hydration shell; and (iii) the relative influence of van der Waals (dispersion) and electrostatic interactions on hydration remains unclear. We investigate this connection using spectroscopic, classical simulation and ab initio methods by following the transition from hydrophile to hydrophobe induced by the step-wise fluorination of methyl groups.

Publisher Correction: Imaging single glycans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Imaging single glycans.

Imaging of biomolecules guides our understanding of their diverse structures and functions. Real-space imaging at sub-nanometre resolution using cryo-electron microscopy has provided key insights into proteins and their assemblies. Direct molecular imaging of glycans-the predominant biopolymers on Earth, with a plethora of structural and biological functions-has not been possible so far.

Cooperativity and ion pairing in magnesium sulfate aqueous solutions from the dilute regime to the solubility limit.

We report a terahertz absorption spectroscopy study of MgSO4 aqueous solutions in the concentration range 0.1 mol dm-3 to 2.4 mol dm-3.

Physical and chemical properties of seawater during 2013-2015 in the 400 m water column in the northern Gulf of Aqaba, Red Sea.

This research investigated physical (temperature, salinity, and density) and chemical (dissolved oxygen, ammonium, nitrate, nitrite, phosphate, and silicate) properties of offshore seawater in the Red Sea northern Gulf of Aqaba; Jordanian Site were measured during 2013-2015 to assess the temporal and seasonal variation of the upper 400 m of the water column. The study also investigated seasonal variations, assessing the relationships of temperature with physical and chemical parameters. The average value of temperature for all data was 23.

Hydrophobic but Water-Friendly: Favorable Water-Perfluoromethyl Interactions Promote Hydration Shell Defects.

Although perfluorination is known to enhance hydrophobicity and change protein activity, its influence on hydration-shell structure and thermodynamics remains an open question. Here we address that question by combining experimental Raman multivariate curve resolution spectroscopy with theoretical classical simulations and quantum mechanical calculations. Perfluorination of the terminal methyl group of ethanol is found to enhance the disruption of its hydration-shell hydrogen bond network.

Advancing Solutions to the Carbohydrate Sequencing Challenge.

Carbohydrates possess a variety of distinct features with stereochemistry playing a particularly important role in distinguishing their structure and function. Monosaccharide building blocks are defined by a high density of chiral centers. Additionally, the anomericity and regiochemistry of the glycosidic linkages carry important biological information.

Tailoring the Chemical Modification of Chitosan Hydrogels to Fine-Tune the Release of a Synergistic Combination of Chemotherapeutics.

Combination chemotherapy with a defined ratio and sequence of drug release is a clinically established and effective route to treat advanced solid tumors. In this context, a growing body of literature demonstrates the potential of hydrogels constructed with chemically modified polysaccharides as depots for controlled release of chemotherapeutics. Identifying the appropriate modification in terms of physicochemical properties of the functional group and its degree of substitution (χ) to achieve the desired release profile for multiple drugs is, however, a complex multivariate problem.

Unexpected trends in the hydrophobicity of fluorinated amino acids reflect competing changes in polarity and conformation.

Fluorination can dramatically improve the thermal and proteolytic stability of proteins and their enzymatic activity. Key to the impact of fluorination on protein properties is the hydrophobicity of fluorinated amino acids. We use molecular dynamics simulations, together with a new fixed-charge, atomistic force field, to quantify the changes in hydration free energy, ΔGHyd, for amino acids with alkyl side chains and with 1 to 6 -CH → -CF side chain substitutions.

Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients.

A molecular dynamics model for glycosylphosphatidyl-inositol anchors: "flop down" or "lollipop"?

We present a computational model of glycosylphosphatidyl-inositol (GPI) anchors for molecular dynamics studies. The model is based on state-of-the-art biomolecular force fields from the AMBER family, employing GLYCAM06 for carbohydrates and Lipid14 to represent fatty acid tails. We construct an adapted glycero-phosphatidyl-inositol unit to establish a seamless transition between the two domains of atom types.

Correction: Developing force fields when experimental data is sparse: AMBER/GAFF-compatible parameters for inorganic and alkyl oxoanions.

Correction for 'Developing force fields when experimental data is sparse: AMBER/GAFF-compatible parameters for inorganic and alkyl oxoanions' by Sadra Kashefolgheta et al., Phys. Chem.

Chemoselective Photoredox Synthesis of Unprotected Primary Amines Using Ammonia.

Unprotected α-amino carbon radicals are produced as novel intermediates via a transformation that merges acid-promoted N-H imine generation and chemoselective photocatalytic single-electron reduction. Coupling ammonia and aldehydes/ketones allows the generation of primary amines under mild conditions without the need for protecting groups. The key intermediate can be efficiently transformed into primary (di)amines by a formal dimerization, reductive amination via hydrogen atom transfer, and arylation through radical-radical coupling.

A Two-Dimensional Polymer Synthesized at the Air/Water Interface.

A trifunctional, partially fluorinated anthracene-substituted triptycene monomer was spread at an air/water interface into a monolayer, which was transformed into a long-range-ordered 2D polymer by irradiation with a standard UV lamp. The polymer was analyzed by Brewster angle microscopy, scanning tunneling microscopy measurements, and non-contact atomic force microscopy, which confirmed the generation of a network structure with lattice parameters that are virtually identical to a structural model network based on X-ray diffractometry of a closely related 2D polymer. The nc-AFM images highlight the long-range order over areas of at least 300×300 nm .

Synthesis of Carbon-Nitrogen-Phosphorous Materials with an Unprecedented High Amount of Phosphorous toward an Efficient Fire-Retardant Material.

Phosphorus incorporation into carbon can greatly modify its chemical, electronic, and thermal stability properties. To date this has been limited to low levels of phosphorus. Now a simple, large-scale synthesis of carbon-nitrogen-phosphorus (CNP) materials is reported with tunable elemental composition, leading to excellent thermal stability to oxidation and fire-retardant properties.

Formation and Properties of Poly(Ionic Liquid)-Carbene Nanogels Containing Individually Stabilized Silver Species.

Imidazolium-based ionic liquids have the ability to undergo a variety of chemical reactions through an N-heterocyclic carbene (NHC) intermediate, which has expanded the chemical toolbox for new applications. Despite their uses and exploration, the carbene-forming properties and applications of their polymeric congeners, poly(ionic liquid)s (PILs), is still underdeveloped. Herein, we explore the NHC-forming properties of a theophylline-derived PIL for nanogel synthesis.

Literally Green Chemical Synthesis of Artemisinin from Plant Extracts.

Active pharmaceutical ingredients are either extracted from biological sources-where they are synthesized in complex, dynamic environments-or prepared in stepwise chemical syntheses by reacting pure reagents and catalysts under controlled conditions. A combination of these two approaches, where plant extracts containing reagents and catalysts are utilized in intensified chemical syntheses, creates expedient and sustainable processes. We illustrate this principle by reacting crude plant extract, oxygen, acid, and light to produce artemisinin, a key active pharmaceutical ingredient of the most powerful antimalarial drugs.

Functional Biocompatible Matrices from Mussel Byssus Waste.

The mussel byssus is a biorenewable, protein-based material produced by marine mussels, which has attracted the interest of material scientists because of its remarkable mechanical and self-healing properties. Large quantities of byssus waste material from mussel mariculture are produced every year, which have great potential as a raw starting material for producing sustainable advanced materials. In this work, we developed a facile and scalable method to synthesize whole byssus-based porous matrices that retain part of the hierarchical organization of the pristine material at the nanoscale.

Thioimidazolium Ionic Liquids as Tunable Alkylating Agents.

Alkylating ionic liquids based on the thioimidazolium structure combine the conventional properties of ionic liquids, including low melting point and nonvolatility, with the alkylating function. Alkyl transfer occurs exclusively from the S-alkyl position, thus allowing for easy derivatization of the structure without compromising specificity. We apply this feature to tune the electrophilicty of the cation to profoundly affect the reactivity of these alkylating ionic liquids, with a caffeine-derived compound possessing the highest reactivity.

A "Cell-Friendly" Window for the Interaction of Cells with Hyaluronic Acid/Poly-l-Lysine Multilayers.

Polyelectrolyte multilayers assembled from hyaluronic acid (HA) and poly-l-lysine (PLL) are most widely studied showing excellent reservoir characteristics to host molecules of diverse nature; however, thick (HA/PLL) films are often found cell repellent. By a systematic study of the adhesion and proliferation of various cells as a function of bilayer number "n" a correlation with the mechanical and chemical properties of films is developed. The following cell lines have been studied: mouse 3T3 and L929 fibroblasts, human foreskin primary fibroblasts VH-Fib, human embryonic kidney HEK-293, human bone cell line U-2-OS, Chinese hamster ovary CHO-K and mouse embryonic stem cells.