Sources of PM-Associated Health Risks in Europe and Corresponding Emission-Induced Changes During 2005-2015.

We present a newly developed approach to characterize the sources of fine particulate matter (PM)-related premature deaths in Europe using the chemical transport model GEOS-Chem and its adjoint. The contributions of emissions from each individual country, species, and sector are quantified and mapped out at km scale. In 2015, total PM-related premature death is estimated to be 449,813 (257,846-722,138) in Europe, 59.

Reclaimed and Up-Cycled Cathodes for Lithium-Ion Batteries.

As electric vehicles become more widely used, there is a higher demand for lithium-ion batteries (LIBs) and hence a greater incentive to find better ways to recycle these at their end-of-life (EOL). This work focuses on the process of reclamation and re-use of cathode material from LIBs. Black mass containing mixed LiMnO and NiCoAlO from a Nissan Leaf pouch cell are recovered via two different recycling routes, shredding or disassembly.

The primary familial brain calcification-associated protein MYORG is an α-galactosidase with restricted substrate specificity.

Primary familial brain calcification (PFBC) is characterised by abnormal deposits of calcium phosphate within various regions of the brain that are associated with severe cognitive impairments, psychiatric conditions, and movement disorders. Recent studies in diverse populations have shown a link between mutations in myogenesis-regulating glycosidase (MYORG) and the development of this disease. MYORG is a member of glycoside hydrolase (GH) family 31 (GH31) and, like the other mammalian GH31 enzyme α-glucosidase II, this enzyme is found in the lumen of the endoplasmic reticulum (ER).

Inverting the Stereoselectivity of an NADH-Dependent Imine-Reductase Variant.

Imine reductases (IREDs) offer biocatalytic routes to chiral amines and have a natural preference for the NADPH cofactor. In previous work, we reported enzyme engineering of the ()-selective IRED from (NADH-IRED-) yielding a NADH-dependent variant with high catalytic efficiency. However, no IRED with NADH specificity and ()-selectivity in asymmetric reductions has yet been reported.

A Four Carbon Organonitrate as a Significant Product of Secondary Isoprene Chemistry.

Oxidation of isoprene by nitrate radicals (NO) or by hydroxyl radicals (OH) under high NO conditions forms a substantial amount of organonitrates (ONs). ONs impact NO concentrations and consequently ozone formation while also contributing to secondary organic aerosol. Here we show that the ONs with the chemical formula CHNO are a significant fraction of isoprene-derived ONs, based on chamber experiments and ambient measurements from different sites around the globe.

Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications.

Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked -acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated.

Global Cancer Risk From Unregulated Polycyclic Aromatic Hydrocarbons.

In assessments of cancer risk from atmospheric polycyclic aromatic hydrocarbons (PAHs), scientists and regulators rarely consider the complex mixture of emitted compounds and degradation products, and they often represent the entire mixture using a single emitted compound-benzo[a]pyrene. Here, we show that benzo[a]pyrene is a poor indicator of PAH risk distribution and management: nearly 90% of cancer risk worldwide results from other PAHs, including unregulated degradation products of emitted PAHs. We develop and apply a global-scale atmospheric model and conduct health impact analyses to estimate human cancer risk from 16 PAHs and several of their N-PAH degradation products.

Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways.

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the ()- or the ()-enantiomer of phenylethanol.

Global Importance of Hydroxymethanesulfonate in Ambient Particulate Matter: Implications for Air Quality.

Sulfur compounds are an important constituent of particulate matter, with impacts on climate and public health. While most sulfur observed in particulate matter has been assumed to be sulfate, laboratory experiments reveal that hydroxymethanesulfonate (HMS), an adduct formed by aqueous phase chemical reaction of dissolved HCHO and SO, may be easily misinterpreted in measurements as sulfate. Here we present observational and modeling evidence for a ubiquitous global presence of HMS.

Effects of Sea Salt Aerosol Emissions for Marine Cloud Brightening on Atmospheric Chemistry: Implications for Radiative Forcing.

Marine cloud brightening (MCB) is proposed to offset global warming by emitting sea salt aerosols to the tropical marine boundary layer, which increases aerosol and cloud albedo. Sea salt aerosol is the main source of tropospheric reactive chlorine (Cl ) and bromine (Br ). The effects of additional sea salt on atmospheric chemistry have not been explored.

Deep Eutectic Solvents Based on Natural Ascorbic Acid Analogues and Choline Chloride.

Deep eutectic solvents (DES) are one of the most promising green technologies to emerge in recent years given their combination of environmentally friendly credentials and useful functionalities. Considering the continued search for new DES - especially those that exemplify the aforementioned characteristics, we report the preparation of DES based on natural analogues of l-ascorbic acid for the first time. The onset of eutectic melting occurred at temperatures far below the melting point of the individual components and resulted in the generation of glass forming fluids with glass transition temperatures, viscosities and flow behavior that are comparable to similar systems.

Investigation of Parameters that Affect Resin Swelling in Green Solvents.

The influence of various physical and chemical factors on the swelling of polystyrene and PEG based resins in greener organic solvents has been systematically investigated. In general, chemical factors: the nature of the functionality/linker and the degree of loading were found to have a far larger influence on the swelling of the resins than physical parameters such as bead size. The results are interpreted in terms of Hansen solubility parameters for the solvents and there is evidence that some solvents interact with the polymeric core of a resin whilst others interact with the functionality.

NAD(P)H-Dependent Dehydrogenases for the Asymmetric Reductive Amination of Ketones: Structure, Mechanism, Evolution and Application.

Asymmetric reductive aminations are some of the most important reactions in the preparation of active pharmaceuticals, as chiral amines feature in many of the world's most important drugs. Although many enzymes have been applied to the synthesis of chiral amines, the development of reductive amination reactions that use enzymes is attractive, as it would permit the one-step transformation of readily available prochiral ketones into chiral amines of high optical purity. However, as most natural "reductive aminase" activities operate on keto acids, and many are able to use only ammonia as the amine donor, there is considerable scope for the engineering of natural enzymes for the reductive amination of ketones, and also for the preparation of secondary amines using alkylamines as donors.

Conserved Histidine Adjacent to the Proximal Cluster Tunes the Anaerobic Reductive Activation of Membrane-Bound [NiFe] Hydrogenase-1.

[NiFe] hydrogenases are electrocatalysts that oxidize H at a rapid rate without the need for precious metals. All membrane-bound [NiFe] hydrogenases (MBH) possess a histidine residue that points to the electron-transfer iron sulfur cluster closest ("proximal") to the [NiFe] H-binding active site. Replacement of this amino acid with alanine induces O sensitivity, and this has been attributed to the role of the histidine in enabling the reversible O-induced over-oxidation of the [FeSCys] proximal cluster possessed by all O-tolerant MBH.

Extending the Scope of F Hyperpolarization through Signal Amplification by Reversible Exchange in MRI and NMR Spectroscopy.

Fluorinated ligands have a variety of uses in chemistry and industry, but it is their medical applications as F-labelled positron emission tomography (PET) tracers where they are most visible. In this work, we illustrate the potential of using F-containing ligands as future magnetic resonance imaging (MRI) contrast agents and as probes in magnetic resonance spectroscopy studies by significantly increasing their magnetic resonance detectability through the signal amplification by reversible exchange (SABRE) hyperpolarization method. We achieve F SABRE polarization in a wide range of molecules, including those essential to medication, and analyze how their steric bulk, the substrate loading, polarization transfer field, pH, and rate of ligand exchange impact the efficiency of SABRE.

A Cu-Catalysed Radical Cross-Dehydrogenative Coupling Approach to Acridanes and Related Heterocycles.

The synthesis of acridanes and related compounds through a Cu-catalysed radical cross-dehydrogenative coupling of simple 2-[2-(arylamino)aryl]malonates is reported. This method can be further streamlined to a one-pot protocol involving the in situ fomation of the 2-[2-(arylamino)aryl]malonate by α-arylation of diethyl malonate with 2-bromodiarylamines under Pd catalysis, followed by Cu-catalysed cyclisation.

Structural and functional insight into human O-GlcNAcase.

O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.

Structural evidence for glutathione transferase GSTF2 functioning as a transporter of small organic ligands.

Glutathione transferases (GSTs) are involved in many processes in plant biochemistry, with their best characterised role being the detoxification of xenobiotics through their conjugation with glutathione. GSTs have also been implicated in noncatalytic roles, including the binding and transport of small heterocyclic ligands such as indole hormones, phytoalexins and flavonoids. Although evidence for ligand binding and transport has been obtained using gene deletions and ligand binding studies on purified GSTs, there has been no structural evidence for the binding of relevant ligands in noncatalytic sites.

Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent Protein-Ligand Interactions.

A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC-SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein.

E. coli cells expressing the Baeyer-Villiger monooxygenase 'MO14' (ro03437) from Rhodococcus jostii RHA1 catalyse the gram-scale resolution of a bicyclic ketone in a fermentor.

The Baeyer-Villiger monooxygenase (BVMO) 'MO14' from Rhodococcus jostii RHA1, is an enantioselective BVMO that catalyses the resolution of the model ketone substrate bicyclo[3.2.0]hept-2-en-6-one to the (1S,5R)-2-oxa lactone and the residual (1S,5R)-substrate enantiomer.

Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.

Background: Glyoxalase II, the second of two enzymes in the glyoxalase system, is a thiolesterase that catalyses the hydrolysis of S-D-lactoylglutathione to form glutathione and D-lactic acid.

Results: The structure of human glyoxalase II was solved initially by single isomorphous replacement with anomalous scattering and refined at a resolution of 1.9 A.