Nucleophilic Substitution at Tetracoordinate Phosphorus. Stereochemical Course and Mechanisms of Nucleophilic Displacement Reactions at Phosphorus in Diastereomeric cis- and trans-2-Halogeno-4-methyl-1,3,2-dioxaphosphorinan-2-thiones: Experimental and DFT Studies

Geometrical cis- and trans- isomers of 2-chloro-, 2-bromo- and 2-fluoro-4-methyl-1,3,2-dioxaphosphorinan-2-thiones were obtained in a diastereoselective way by (a) sulfurization of corresponding cyclic P^III-halogenides, (b) reaction of cyclic phosphorothioic acids with phosphorus pentachloride and (c) halogen–halogen exchange at P^IV-halogenide. Their conformation and configuration at the C₄-ring carbon and phosphorus stereocentres were studied by NMR (¹H, ³¹P) methods, X-ray analysis and density functional (DFT) calculations. The stereochemistry of displacement reactions (alkaline hydrolysis, methanolysis, aminolysis) at phosphorus and its mechanism were shown to depend on the nature of halogen. Cyclic cis- and trans-isomers of chlorides and bromides react with nucleophiles (HO⁻, CH₃O⁻, Me₂NH) with inversion of configuration at phosphorus. DFT calculations provided evidence that alkaline hydrolysis of cyclic thiophosphoryl chlorides proceeds according to the S_N2-P mechanism with a single transition state according to the potential energy surface (PES) observed. The alkaline hydrolysis reaction of cis- and trans-fluorides afforded the same mixture of the corresponding cyclic thiophosphoric acids with the thermodynamically more stable major product. Similar DFT calculations revealed that substitution at phosphorus in fluorides proceeds stepwise according to the A–E mechanism with formation of a pentacoordinate intermediate since a PES with two transition states was observed.     

Indirectly Detected DNP-Enhanced 17O NMR Spectroscopy: Observation of Non-Protonated Near-Surface Oxygen at Naturally Abundant Silica and Silica-Alumina

Recent studies have shown that dynamic nuclear polarization (DNP) can be used to detect ¹⁷O solid-state NMR spectra of naturally abundant samples within a reasonable experimental time. Observations using indirect DNP, which relies on ¹H mediation in transferring electron hyperpolarization to ¹⁷O, are currently limited mostly to hydroxyls. Direct DNP schemes can hyperpolarize non-protonated oxygen near the radicals; however, they generally offer much lower signal enhancements. In this study, we demonstrate the detection of signals from non-protonated ¹⁷O in materials containing silicon. The sensitivity boost that made the experiment possible originates from three sources: indirect DNP excitation of ²⁹Si via protons, indirect detection of ¹⁷O through ²⁹Si nuclei using two-dimensional ²⁹Si{¹⁷O} D-HMQC, and Carr-Purcell-Meiboom-Gill refocusing of ²⁹Si magnetization during acquisition. This ²⁹Si-detected scheme enabled, for the first time, 2D ¹⁷O−²⁹Si heteronuclear correlation spectroscopy in mesoporous silica and silica-alumina surfaces at natural abundance. In contrast to the silanols showing motion-averaged ¹⁷O signals, the framework oxygens exhibit unperturbed powder patterns as unambiguous fingerprints of surface sites. Along with hydroxyl oxygens, detection of these moieties will help in gaining more atomistic-scale insights into surface chemistry.     

Searching for Potential Markers of Glomerulopathy in Urine by HS-SPME-GC×GC TOFMS

Volatile organic compounds (VOCs) exiting in urine are potential biomarkers of chronic kidney diseases. Headspace solid phase microextraction (HS-SPME) was applied for extraction VOCs over the urine samples. Volatile metabolites were separated and identified by means of two-dimensional gas chromatography and time of flight mass spectrometry (GC × GC TOF MS). Patients with glomerular diseases (n = 27) and healthy controls (n = 20) were recruited in the study. Different VOCs profiles were obtained from patients and control. Developed methodology offers the opportunity to examine the metabolic profile associated with glomerulopathy. Four compounds found in elevated amounts in the patients group, i.e., methyl hexadecanoate; 9-hexadecen-1-ol; 6,10-dimethyl-5,9-undecadien-2-one and 2-pentanone were proposed as markers of glomerular diseases.     

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.     

Role of Gut Microbiota,Probiotics and Prebiotics in the Cardiovascular Diseases

In recent years, there has been a growing interest in identifying and applying new, naturally occurring molecules that promote health. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host”. Quite a few fermented products serve as the source of probiotic strains, with many factors influencing the effectiveness of probiotics, including interactions of probiotic bacteria with the host’s microbiome. Prebiotics contain no microorganisms, only substances which stimulate their growth. Prebiotics can be obtained from various sources, including breast milk, soybeans, and raw oats, however, the most popular prebiotics are the oligosaccharides contained in plants. Recent research increasingly claims that probiotics and prebiotics alleviate many disorders related to the immune system, cancer metastasis, type 2 diabetes, and obesity. However, little is known about the role of these supplements as important dietary components in preventing or treating cardiovascular disease. Still, some reports and clinical studies were conducted, offering new ways of treatment. Therefore, the aim of this review is to discuss the roles of gut microbiota, probiotics, and prebiotics interventions in the prevention and treatment of cardiovascular disease.     

Optical coherence tomography with plasmon resonant nanorods of gold

We explored plasmon resonant nanorods of gold as a contrast agent for optical coherence tomography (OCT). Nanorod suspensions were generated through wet chemical synthesis and characterized with spectrophotometry, transmission electron microscopy, and OCT. Polyacrylamide-based phantoms were generated with appropriate scattering and anisotropy coefficients (30 cm(-1) and 0.89, respectively) to image distribution of the contrast agent in an environment similar to that of tissue. The observed signal was dependent on whether the plasmon resonance peak overlapped the source bandwidth of the OCT, confirming the resonant character of enhancement. Gold nanorods with plasmon resonance wavelengths overlapping the OCT source yielded a signal-to-background ratio of 4.5 dB, relative to the tissue phantom. Strategies for OCT imaging with nanorods are discussed.     

Route to Lambda in conformally coupled phantom cosmology

In this Letter we investigate acceleration in the flat cosmological model with a conformally coupled phantom field and we show that acceleration is its generic feature. We reduce the dynamics of the model to a 3-dimensional dynamical system and analyze it on a invariant 2-dimensional submanifold. Then the concordance FRW model with the cosmological constant Λ   is a global attractor situated on a 2-dimensional invariant space. We also study the behaviour near this attractor, which can be approximated by the dynamics of the linearized part of the system. We demonstrate that trajectories of the conformally coupled phantom scalar field with a simple quadratic potential crosses the cosmological constant barrier infinitely many times in the phase space. The universal behaviour of the scalar field and its potential is also calculated. We conclude that the phantom scalar field conformally coupled to gravity gives a natural dynamical mechanism of concentration of the equation of state coefficient around the magical value weff=−1$w_{\mathrm{eff}}=-1$. We demonstrate route to Lambda through the infinite times crossing the weff=−1$w_{\mathrm{eff}}=-1$ phantom divide.     

Boron- versus Nitrogen-Centered Nucleophilic Reactivity of (Cyano)hydroboryl Anions: Synthesis of Cyano(hydro)organoboranes and 2-Aza-1,4-diborabutatrienes

Cyclic alkyl(amino)carbene-stabilized (cyano)hydroboryl anions were synthesized by deprotonation of (cyano)dihydroborane precursors. While they display boron-centered nucleophilic reactivity towards organohalides, generating fully unsymmetrically substituted cyano(hydro)organoboranes, they show cyano-nitrogen-centered nucleophilic reactivity towards haloboranes, resulting in the formation of hitherto unknown linear 2-aza-1,4-diborabutatrienes.     

Novel poly(lactic acid)–poly(ethylene oxide) chain‐linked copolymer and its application in nano‐encapsulation

The work presented here investigates the synthesis of poly(lactic acid)–poly(ethylene oxide) diisocyanate chain‐linked copolymer, and its application in the nano‐encapsulation of bioactive compounds. Study was conducted on the effect of the type of chain‐linking agent, along with molecular weight, thermal properties and hydrophilic/hydrophobic behavior, through the methods of gel permeation chromatography, Fourier transform infrared spectroscopy–attenuated total reflectance, differential scanning calorimetry, light scattering, water uptake experimentation, and water contact angle measurements. Nanoparticle formation was performed via a single solvent evaporation process, and the particles obtained were characterized by dynamic light scattering and scanning electron microscopy. Results show the significantly enhanced molecular weight of the final product after the chain‐linking reaction (up to 300,000 g/mol), as well as the non‐linear nature of the sample due to broad polydispersity, ranging from 4–13. The final products exhibited glass transition temperatures of between 30 and 44 °C, while their crystalline quality was either significantly suppressed or a completely amorphous attribute was observed. Nanoparticles in the range of 300 nm that contained metazachlor were successfully prepared, and their releasing behavior exhibited first order release kinetics. A slower rate of release was observed in samples containing 4,4′‐methylenebis(phenyl isocyanate) as a chain‐linker. Copyright © 2014 John Wiley & Sons, Ltd.     

Peptides derivatized with bicyclic quaternary ammonium ionization tags. Sequencing via tandem mass spectrometry

Improving the sensitivity of detection and fragmentation of peptides to provide reliable sequencing of peptides is an important goal of mass spectrometric analysis. Peptides derivatized by bicyclic quaternary ammonium ionization tags: 1‐azabicyclo[2.2.2]octane (ABCO) or 1,4‐diazabicyclo[2.2.2]octane (DABCO), are characterized by an increased detection sensitivity in electrospray ionization mass spectrometry (ESI‐MS) and longer retention times on the reverse‐phase (RP) chromatography columns. The improvement of the detection limit was observed even for peptides dissolved in 10 mM NaCl. Collision‐induced dissociation tandem mass spectrometry of quaternary ammonium salts derivatives of peptides showed dominant a‐ and b‐type ions, allowing facile sequencing of peptides. The bicyclic ionization tags are stable in collision‐induced dissociation experiments, and the resulted fragmentation pattern is not significantly influenced by either acidic or basic amino acid residues in the peptide sequence. Obtained results indicate the general usefulness of the bicyclic quaternary ammonium ionization tags for ESI‐MS/MS sequencing of peptides. Copyright © 2014 John Wiley & Sons, Ltd.