A multi-platform approach for the comprehensive analysis of per- and polyfluoroalkyl substances (PFAS) and fluorine mass balance in commercial ski wax products.

The unique properties of per- and polyfluoroalkyl substances (PFAS) have led to their extensive use in consumer products, including ski wax. Based on the risks associated with PFAS, and to align with PFAS regulations, the international ski federation (FIS) implemented a ban on products containing "C fluorocarbons/perfluorooctanoate (PFOA)" at all FIS events from the 2021/2022 season, leading manufactures to shift their formulations towards short-chain PFAS chemistries. To date, most studies characterising PFAS in ski waxes have measured a suite of individual substances using targeted analytical approaches.

Accelerative Solid-State Oxidation Behaviour of Amorphous and Partially Crystalline Venetoclax.

There is a growing focus on solid-state degradation, especially for its relevance in understanding interactions with excipients. Performing a solid-state degradation of Venetoclax (VEN), we delve into VEN's stability in different solid-state oxidative stress conditions, utilizing Peroxydone™ complex and urea peroxide (UHP). The investigation extends beyond traditional forced degradation scenarios, providing insights into VEN's behavior over 32 h, considering temperature and crystallinity conditions.

Identifying Exchangeable Protons in a 1D NMR Spectrum by Spatially Selective Exchange-Editing.

The front cover artwork is provided by Markus Rotzinger at the University of Graz, Austria. The front cover picture illustrates the way the 1D exchange-editing NMR method makes exchanging protons visible by sign alteration. The depicted spectrum of D-glucose shows all exchanging signals inverted, thus allowing a fast qualitative determination, potentially in a single scan.

Antimicrobial macrozones interact with biological macromolecules via two-site binding mode of action: Fluorimetric, NMR and docking studies.

Macrozones are novel conjugates of azithromycin and thiosemicarbazones, which exhibit very good in vitro antibacterial activities against susceptible and some resistant bacterial strains thus showing a potential for further development. A combination of spectrometric (fluorimetry, STD and WaterLOGSY NMR) and molecular docking studies provided insights into atomic details of interactions between selected macrozones and biological receptors such as E. coli ribosome and bovine serum albumin.

Identifying Exchangeable Protons in a 1D NMR Spectrum by Spatially Selective Exchange-Editing.

Signals undergoing chemical or conformational exchange in one-dimensional NMR spectra are often identified by deuterium exchange. In order to obtain quantitative information about the dynamic processes involved, one frequently used method is EXchange SpectroscopY (EXSY). To detect all exchange processes, the EXSY experiment requires the acquisition of time-consuming two-dimensional spectra.

ToxRS bile sensing system.

The seventh pandemic of the diarrheal cholera disease, which began in 1960, is caused by the Gram-negative bacterium . Its environmental persistence provoking recurring sudden outbreaks is enabled by rapid adaption to changing environments involving sensory proteins like ToxR and ToxS. Located at the inner membrane, ToxR and ToxS react to environmental stimuli like bile acid, thereby inducing survival strategies for example bile resistance and virulence regulation.

The membrane-binding bacterial toxin long direct repeat D inhibits protein translation.

Bacterial plasmids and chromosomes widely contain toxin-antitoxin (TA) loci, which are implicated in stress response, growth regulation and even tolerance to antibiotics and environmental stress. Type I TA systems consist of a stable toxin-expressing mRNA, which is counteracted by an unstable RNA antitoxin. The Long Direct Repeat (LDR-) D locus, a type I TA system of Escherichia Coli (E.

High-Performance Thermoplastics from a Unique Bicyclic Lignin-Derived Diol.

Polyesters are an important class of thermoplastic polymers, and there is a clear demand to find high-performing, recyclable, and renewable alternatives. In this contribution, we describe a range of fully bio-based polyesters obtained upon the polycondensation of the lignin-derived bicyclic diol 4,4'-methylenebiscyclohexanol (MBC) with various cellulose-derived diesters. Interestingly, the use of MBC in combination with either dimethyl terephthalate (DMTA) or dimethyl furan-2,5-dicarboxylate (DMFD) resulted in polymers with industrially relevant glass transition temperatures in the 103-142 °C range and high decomposition temperatures (261-365 °C range).

Influence of PLGA End Groups on the Release Profile of Dexamethasone from Ocular Implants.

The present study deals with the development of dexamethasone (DM)-loaded implants using ester end-capped Resomer RG 502 poly(lactic acid-co-glycolic acid) (PLGA) (502), acid end-capped Resomer RG 502H PLGA (502H), and a 502H:502 mixture (3:1) via hot melt extrusion (HME). The prepared intravitreal implants (20 and 40% DM loaded in each PLGA) were thoroughly investigated to determine the effect of different end-capped PLGA and drug loading on the long-term release profile of DM. The implants were characterized for solid-state active pharmaceutical ingredient (APIs) using DSC and SWAXS, water uptake during stability study, the crystal size of API in the implant matrix using hot-stage polarized light microscopy, and in vitro release profile.

Quantitative chemical profiling of cellulose acetate excipient via C NMR spectroscopy in controlled release formulations.

Cellulose acetate (CA) is the main component of controlled-release (CR) coating of formulations such as osmotic-controlled release oral delivery system (OROS) and CR microspheres. Despite multiple applications, there are limited or no reports dealing with the characterization and quantification of CA in the formulated systems. Thus, the present investigation deals with the development of the Quantitative Carbon-13 Nuclear Magnetic Resonance (qCNMR) spectroscopy method for the determination of CA amount in the CR microsphere formulations.

Overexpression of recombinant proteins containing non-canonical amino acids in Vibrio natriegens: p-azido-L-phenylalanine as coupling site for F-tags.

Vibrio natriegens is the fastest growing organism identified so far. The minimum doubling time of only 9.4 min, the ability to utilize over 60 different carbon sources and its non-pathogenic properties make it an interesting alternative to E.

Phase Behavior of Drug-Lipid-Surfactant Ternary Systems toward Understanding the Annealing-Induced Change.

The present study systematically investigates the effect of annealing conditions and the Kolliphor P 407 content on the physicochemical and structural properties of Compritol (glyceryl behenate) and ternary systems prepared via melt cooling (Kolliphor P 407, Compritol, and a hydrophilic API) representing solid-lipid formulations. The physical properties of Compritol and the ternary systems with varying ratios of Compritol and Kolliphor P 407 were characterized using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS) and infrared (IR) spectroscopy, and hot-stage microscopy (HSM), before and after annealing. The change in the chemical profiles of different Compritol components as a function of annealing was evaluated using H NMR spectroscopy.

Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?

The generation of peroxynitrite (ONOO) is associated with several diseases, including atherosclerosis, hypertension, neurodegeneration, cancer, inflammation, and sepsis. Alpha-ketoglutarate (αKG) is a known potential highly antioxidative agent for radical oxidative species such as peroxides. The question arises as to whether αKG is also a potential scavenger of ONOO and a potential protector against ONOO-mediated nitration of proteins.

Structural and DNA-binding properties of the cytoplasmic domain of Vibrio cholerae transcription factor ToxR.

ToxR represents an essential transcription factor of Vibrio cholerae, which is involved in the regulation of multiple, mainly virulence associated genes. Its versatile functionality as activator, repressor or coactivator suggests a complex regulatory mechanism, whose clarification is essential for a better understanding of the virulence expression system of V. cholerae.

The periplasmic domains of Vibriocholerae ToxR and ToxS are forming a strong heterodimeric complex independent on the redox state of ToxR cysteines.

The transmembrane protein ToxR plays a key role in the virulence expression system of Vibrio cholerae. The activity of ToxR is dependent on its periplasmic sensor domain (ToxRp) and on the inner membrane protein ToxS. Herein, we present the Nuclear Magnetic Resonance NMR solution structure of the sensory ToxRp containing an intramolecular disulfide bond.

Structural Fuzziness of the RNA-Organizing Protein SERF Determines a Toxic Gain-of-interaction.

The mechanisms by which protein complexes convert from functional to pathogenic are the subject of intensive research. Here, we report how functionally unfavorable protein interactions can be induced by structural fuzziness, i.e.

Solvent-independent determination of heteroatom protonation states from NMR spectra by differential deuterium isotope shifts.

The NMR-spectroscopy based structure elucidation of organic molecules containing heteroatoms is often obstructed by the difficulties in determining the heteroatom protonation states. Here we describe a simple but broadly applicable approach for the determination of the protonation states of heteroatoms. Differential deuterium isotope shifts observed upon the addition of small amounts of H2O or D2O to any solvent can be used to determine the protonation states of heteroatoms.

A small molecule chaperone rescues the stability and activity of a cancer-associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a human FAD-dependent enzyme that plays a crucial role in the antioxidant defense system. A naturally occurring single-nucleotide polymorphism (NQO1*2) in the NQO1 gene leads to an amino acid substitution (P187S), which severely compromises the activity and stability of the enzyme. The NQO1*2 genotype has been linked to a higher risk for several types of cancer and poor survival rate after anthracycline-based chemotherapy.

Monitoring fast chemical processes by reaction-interrupted excitation transfer (ExTra) NMR spectroscopy.

NMR spectroscopy is generally used to investigate molecules under equilibrium conditions. Despite recent technological and methodogical developments to study on-going reactions, tracing the fate of individual atoms during an irreversible chemical reaction is still a challenging and elaborate task. Reaction-interrupted excitation transfer (ExTra) NMR provides a selective tracking of resonances from atoms, which undergo chemical conversion.

In Situ Observation of Photoswitching by NMR Spectroscopy: A Photochemical Analogue to the Exchange Spectroscopy Experiment.

We present 1D and 2D NMR experiments that provide in situ insights into photoinduced isomerizations. Irradiation during the mixing period of an exchange spectroscopy (EXSY) experiment leads to characteristic cross peaks in 2D spectra. The phototriggered exchange of magnetization occurring in photoswitchable ()- and ()-isomers of three selected azo compounds provides information on the dynamic / equilibria.

Vibrio natriegens: An Alternative Expression System for the High-Yield Production of Isotopically Labeled Proteins.

Isotopic labeling of recombinant proteins is crucial for studying proteins by liquid state NMR spectroscopy. Nowadays, conventional E. coli-based expression systems like BL21 (DE3) are typically used to express recombinant proteins.

Increased Aggregation Tendency of Alpha-Synuclein in a Fully Disordered Protein Complex.

The recent discovery of biologically active fully disordered, so called random fuzzy protein-protein interactions leads to the question of how the high flexibility of these protein complexes correlates to aggregation and pathologic misfolding. We identify the structural mechanism by which a random fuzzy protein complex composed of the intrinsically disordered proteins alpha-Synuclein and SERF1a is able to potentiate cytotoxic aggregation. A structural model derived from an integrated NMR/SAXS analysis of the reconstituted aSyn:SERF1a complex enabled us to observe the partial deprotection of one precise aSyn amyloid nucleation element in the fully unstructured ensemble.

The identification and chromatographic separation of a new highly analogous impurity of the active pharmaceutical ingredient icatibant.

Icatibant is a peptidomimetic drug serving as a bradykinin-receptor antagonist and is approved in Europe and the United States for the treatment of hereditary angioedema attacks. We have detected an impurity with a high structural similarity to icatibant in pharmaceutical dosage forms using an optimized chromatographic method based on reversed phase high performance liquid chromatography with UV detection. The abundance of the impurity was around 1% relative to the icatibant peak following storage at room temperature for 1 month, and raised up to ~16% upon temperature stressing at 100 °C.

Substituting the catalytic proline of 4-oxalocrotonate tautomerase with non-canonical analogues reveals a finely tuned catalytic system.

The enzyme 4-oxalocrotonate tautomerase shows remarkable catalytic versatility due to the secondary amine of its N-terminal proline moiety. In this work, we incorporated a range of proline analogues into the enzyme and examined the effects on structure and activity. While the structure of the enzyme remained unperturbed, its promiscuous Michael-type activity was severely affected.