ABSTRACT
Management of burn injuries is complex, with highly variable outcomes occurring among different populations. This meta-analysis aims to assess the outcomes of burn therapy in North American and European adults, specifically mortality and complications, to guide further therapeutic advances. A systematic review of PubMed, Web of Science, and Cochrane was performed. Random-effect meta-analysis of proportions was conducted to assess the overall prevalence of the defined outcomes. In total, 54 studies were included, pooling 60 269 adult patients. A total of 53 896 patients were in North America (NA, 89.4%), and 6373 were in Europe (10.6%). Both populations experienced similar outcomes. The overall pooled prevalence of mortality was 13% (95% CI, 8%-19%) for moderate burns, 20% (95% CI, 12%-29%) for severe burns in the NA region, and 22% (95% CI, 16%-28%) for severe burns in Europe. Infectious complications were the most common across both regions. European studies showed an infection rate for patients with moderate and severe burns at 8% and 76%, respectively, while NA studies had rates of 35% and 54%. Acute kidney injury (39% vs 37%) and shock (29% vs 35%) were the next most common complications in European and NA studies, respectively. The length of stay was 27.52 days for patients with severe burns in Europe and 31.02 days for patients with severe burns in NA. Burn outcomes are similar between Western populations. While outcomes are reasonably good overall, infectious complications remain high. These findings encourage the development of further therapeutic strategies disclosing respective costs to enable cost/efficiency evaluations in burn management.
Subject(s)
Burns , Humans , Burns/mortality , Burns/therapy , Prevalence , North America/epidemiology , Europe/epidemiologyABSTRACT
13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host-guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the crystallization of host-guest complexes and their crystallographic analysis.
ABSTRACT
This review summarizes achievements in the synthesis of 1,2-disubstituted adamantane derivatives by the construction of the tricyclic framework either by total synthesis or by ring expansion/contraction reactions of corresponding adamantane homologues. It is intended to complement reviews focusing on the preparation of 1,2-disubstituted derivatives by C-H functionalization methods.
ABSTRACT
We report the preparation, characterisation and in vitro tests of hyaluronan fibres containing up to 50 w/w% of temozolomide for local glyoblastoma treatment. These fibres form a hydrogel upon contact with cerebrospinal fluid on the treatment spot.
ABSTRACT
We report a protocol for the one-pot two-step synthesis of noradamantane methylene amines. The first step is the triflic acid-promoted decarboxylation of adamantane carbamates, which causes rearrangement of the adamantane framework to form noradamantane iminium salts, which are reduced to amines in the second separate step.
ABSTRACT
We describe a triflic acid promoted cascade reaction of adamantane derivatives consisting of a decarboxylation of N-methyl protected cyclic carbamates and a subsequent intramolecular nucleophilic 1,2-alkyl shift to generate ring contracted iminium triflates. This reaction expands the family of similar transformations, such as Wagner-Meerwein-, Demjanov-Tiffeneau-, Meinwald- or (semi-)pinacol-rearrangement. It allows the preparation of noradamantane derivatives in a few steps, starting from simple hydroxy-substituted adamantane precursors.
ABSTRACT
We describe a Brønsted acid-catalysed cascade reaction consisting of a Wagner-Meerwein rearrangement and a subsequent intra- or intermolecular Friedel-Crafts reaction leading to adamantane-based heterocycles. In contrast to the reported W.-M. rearrangements, in this case an iminium moiety serves as the acceptor of a migrating nucleophilic alkyl group in a [1,2]-alkyl shift.
ABSTRACT
The stereoselective synthesis of chiral macrocycles bearing two aliphatic amide functional groups is reported. After the amidation mediated by TBD, a guanidine derivative, the olefin transposition step is performed with a slight excess of t-BuOK. The products are afforded in moderate to good combined yields (up to 59%) and with an excellent syn diastereoselectivity (dr > 49 : 1). Introducing enantiopure α-branched substituents was possible and it resulted in mixtures of diastereomers, which could be tested as phase-transfer catalysts using the formation of a phenylalanine analog as a test reaction (up to 43% ee). A clear matched-mismatched situation was observed in the two diastereomeric series.
ABSTRACT
We report a new strategy for the preparation of dirhodium(ii) complexes with the general formula Rh2(A)4 that allows the isolation of a dirhodium tetracarboxylate complex with a free amino group available for postfunctionalization. The postfunctionalization of this complex enables the incorporation of a variety of functional groups, including double and triple bonds as well as nucleophilic moieties, thus paving the way to new classes of polymeric as well as bifunctional catalysts, and polymetallic complexes. Furthermore, we demonstrate that a urea containing dirhodium(ii) complex enables site-selective nitrenoid insertions by remote hydrogen bonding control.
ABSTRACT
The incorporation of diamondoid amino acids (DAAs) into peptide-like drugs is a general strategy to improve lipophilicity, membrane permeability, and metabolic stability of peptidomimetic pharmaceuticals. We designed and synthesized five novel peptidic DAA-containing kinase inhibitors of protein kinaseâ A using a sophisticated molecular dynamics protocol and solid-phase peptide synthesis. By means of a thermophoresis binding assay, NMR, and crystal structure analysis, we determined the influence of the DAAs on the secondary structure and binding affinity in comparison to the native protein kinase inhibitor, which is purely composed of proteinogenic amino acids. Affinity and binding pose are largely conserved. One variant showed 6.5-fold potency improvement, most likely related to its increased side chain lipophilicity. A second variant exhibited slightly decreased affinity presumably due to loss of hydrogen-bond contacts to surrounding water molecules of the first solvation shell.
Subject(s)
Amino Acids/chemistry , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Crystallography, X-Ray , Cyclic AMP-Dependent Protein Kinases/chemistry , Molecular Dynamics SimulationABSTRACT
We have developed a synthesis of 1,2-substituted adamantane carboxylic acids and further bridged cycloalkanes (cage compounds) by palladium acetate-catalyzed C-H bond oxidation. Acetoxylation of cycloalkane framework was performed using picolylamide as a directing group. Modification of the substrate, ligand design and variation of reaction conditions enabled us to study the mechanism of acetoxylation of aliphatic compounds. Post-functionalization reactions and cleavage of the directing group were developed. For the first time the synthesis and characterization of a ß-C3 -tri-substituted adamantane derivatives was achieved.
ABSTRACT
Chitosan/nanohydroxyapatite composites based on scallop shells (CP12, CP14 and CP21) were prepared with different chitosan: nanohydroxyapatite ratios (1:2, 1:4 and 2:1, respectively). Nanohydroxyapatite (P), chitosan(C) and their composites were characterized by means of TGA, XRD, N2 adsorption/desorption analysis, SEM, Zeta potential and FTIR. The BET surface area ranged between 189 and 512â¯m2/g. Static adsorption of Hg+2 was tested for the effect of adsorbent dosage, pH, time and initial Hg+2 concentrations indicating that maximum static adsorption capacity was confirmed by CP12 (111.6â¯mg/g). Static adsorption well fitted with Langmuir adsorption isotherm and Pseudo-second order kinetic models. CP12 was selected for dynamic adsorption of Hg+2 considering the effect of bed height, flow rate and the effect of Hg+2 concentrations. Maximum dynamic adsorption capacity was confirmed at bed height of 3â¯cm, 2.0â¯mL/min flow rate and 300â¯mg/L as Hg+2 concentration with breakthrough time (tb) and exhaustion time (te) of 9 and 21â¯h. Yoon-Nelson and Thomas models best described the experimental Hg+2 breakthrough curve model. After static adsorption, EDTA solution confirmed the maximum desorption efficiency. The validity of CP12 was tested through three cycles of column dynamic adsorption-desorption.
Subject(s)
Chitosan/chemistry , Chitosan/isolation & purification , Durapatite/chemistry , Mercury/chemistry , Mercury/isolation & purification , Nanocomposites/chemistry , Adsorption , Hydrogen-Ion Concentration , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purificationABSTRACT
We have developed a one-step procedure to a variety of chiral lipophilic and conformationally rigid amines and heterocycles by decarboxylation of adamantane-oxazolidine-2-one. Triflic acid or aluminum triflate promote the addition of diverse nucleophiles to the oxazolidine-2-one moiety accompanied by the release of carbon dioxide. The resulting amine or heterocycle is then protonated/metalated by the catalyst (promotor). Additionally, the starting racemic material, adamantane-oxazolidine-2-one, was resolved into single enantiomers using a chiral auxiliary to access enantio-enriched products and to study the racemization pathway of chiral 1,2-disubstituted adamantane derivatives.
ABSTRACT
Chitin and chitosan were obtained by chemical treatments of shrimp shells. Different particle sizes (50-1000 µm) of the raw material were used to study their effect on size distribution, demineralization, deproteinization and deacetylation of chitin and chitosan isolation process. The particle size in the range of 800-1000 µm was selected to isolate chitin, which was achieved by measuring nitrogen, protein, ash, and yield %. Hydrochloric acid (5%, v/v) was optimized in demineralization step to remove the minerals from the starting material. Aqueous solution of sodium hydroxide (5%, w/v) at 90 °C for (20 h) was used in deproteinization step to remove the protein. Pure chitin was consequently impregnated into high concentration of sodium hydroxide (50%) for 3.5 h at 90 °C to remove the acetyl groups in order to form high pure chitosan. The degree of deacetylation (DDA) of chitosan was controlled and evaluated by different analytical tools. The chemical structure of chitin and chitosan was confirmed by elemental analysis, ATR-FTIR, H/C NMR, XRD, SEM, UV-Vis spectroscopy, TGA, and acid-base titration. The isolated chitin and chitosan from shrimp shell showed excellent antibacterial activity against Gram (-ve) bacteria (Escherichia coli) comparing with commercial biopolymers.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chitosan/pharmacology , Animal Shells/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Atlantic Ocean , Brazil , Chitin/isolation & purification , Chitin/pharmacology , Chitin/ultrastructure , Chitosan/isolation & purification , Decapoda/chemistry , Drug Stability , Escherichia coli/drug effects , Microbial Sensitivity Tests , X-Ray DiffractionABSTRACT
The thermodynamically disfavored isomerization of α,ß-unsaturated esters to deconjugated ß,γ-unsaturated analogues occurs readily when coupled to an amidation. Within the framework of macrocyclic derivatives, it is shown that 15, 16, and 18 membered macrocycles react with tBuOK and anilines to generate, in one-pot, ß,γ-unsaturated amides (yields up to 88%). Importantly, single (chiral) diastereomers are isolated (d.r. > 49 : 1, 1H NMR) irrespective of the size and nature of the rings, showing an effective transmission of remote stereochemistry during the isomerization process. CSP-chromatographic resolution and absolute configuration determination by VCD are achieved.
ABSTRACT
Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.
Subject(s)
Alcohols/chemical synthesis , Oligopeptides/chemistry , Alcohols/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
Silver has been used since time immemorial in different chemical form to treat burns, wounds and several different infections caused by pathogenic bacteria, advancement of biological process of nanoparticles synthesis is evolving into a key area of nanotechnology. The current study deals with the green synthesis, characterization, and evaluation of the biological activity and cell viability of hyaluronan fibers with incorporated silver nanoparticles (HA-Ag NPs). Hyaluronan fiber was prepared by the dissolving of sodium hyaluronate (HA) in aqueous alkaline solution to prepare a transparent solution, which was used for the preparation of fibers by a wet-spinning technique. Consequently, hyaluronan fiber was used as capping and stabilizing agent for the preparation of fibers with silver nanoparticles. HA-Ag NPs were confirmed by transmission electron microscopy, dynamic light scattering, UV/VIS spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, thermal analysis, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. HA-Ag NPs showed high antibacterial activity of against Staphylococcus aureus and Escherichia coli. Cell viability tests indicated that hyaluronan, hyaluronan fibers and hyaluronan fibers with silver nanoparticles were non-toxic on the cell growth. Two different particles size of Ag NPs (10, 40 nm) had not any toxicity till the concentration limit. These tests were performed using mouse fibroblast cell line 3T3.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Metal Nanoparticles/chemistry , Silver/chemistry , 3T3 Cells , Animals , Anti-Bacterial Agents/toxicity , Cell Survival/drug effects , Escherichia coli/drug effects , Hyaluronic Acid/toxicity , Mice , Particle Size , Solvents/chemistry , Staphylococcus aureus/drug effectsABSTRACT
Multicatalysts consisting of non-natural oligopeptides with distinctly different catalytic moieties create molecular complexity in a multistep one-pot sequence starting from simple alkenes yielding highly enantiomerically enriched trans-diols.
ABSTRACT
The application of green chemistry in the nano-science and technology is very important in the area of the preparation of various materials. In this work, an eco-friendly chemical method was successfully used for the preparation of hyaluronan fibers containing silver nanoparticles (AgNPs). Thus, hyaluronic acid (HA) was dissolved in an aqueous solution of sodium hydroxide to prepare a transparent solution, which was used for the preparation of fibers by a wet-spinning technique. Consequently, silver nanoparticles inside the fiber were prepared. Different parameters affecting the preparation of final product, such as concentration of silver nitrate, hyaluronan fiber concentration, time and temperature of the reaction, pH of the reaction mixture, were studied. AgNPs were confirmed by transmission electron microscopy (TEM), X-ray diffraction (XRD), two-dimensional X-ray scattering (2D SWAXS), UV/Vis spectroscopy, inductively coupled plasma optical emission spectrometry (ICP OES) and scan electron microscopy (SEM). Mechanical properties of prepared fibers were also measured.