Synthesis of C3-symmetric star shaped amphiphiles for drug delivery applications.

C 3-symmetric star-shaped aromatic compounds are known to possess unique characteristics which facilitate their industrial and biomedical applications. Herein, we report the design, synthesis, self-assembly and drug/dye delivery capabilities of C3-symmetric, hexa-substituted benzene-based amphiphiles. The synthesis of the hexa-substituted C3-symmetric core involves C-acetylation of phloroglucinol to yield the corresponding tri-acetyl derivative. This was further subjected to O-propargylation, followed by the carbonyl reduction of acetyl groups to yield the central core. Various hydrophilic (mPEG) and lipophilic units were then incorporated into this core via click and esterification reactions, respectively, to produce a new type of star shaped amphiphiles. So the obtained amphiphilic architectures have a tendency to aggregate in an aqueous medium forming nanosized assemblies with an inner hydrophobic core, allowing the substituents to control the tension-active properties. The critical aggregation concentration of the amphiphiles was evaluated by fluorescence measurement using the dye Nile red as a fluorescent probe. The hydrodynamic diameter of self-assembled aggregates in aqueous solution was studied by dynamic light scattering, while the actual size and morphology were determined by cryo-transmission electron microscopy (cryo-TEM) analysis. The physicochemical properties of the amphiphiles suggested their suitability for exploring their drug delivery applications. In this endeavor, the amphiphiles were utilized for the encapsulation of model hydrophobic entities and studying their subsequent release from their hydrophobic core in a controlled manner. The transport potential of the synthesised amphiphiles was explored for transdermal drug delivery. Furthermore, cytotoxicity studies were conducted using MCF7 and HeLa cells, which indicated that the nanocarriers had no toxic effect on the cells.

Acute incarcerated intrathoracic sleeve herniation after laparoscopic sleeve gastrectomy: an uncommon yet urgent complication-a comprehensive case report and literature review.

Laparoscopic sleeve gastrectomy (LSG) stands as one of the most frequently performed bariatric procedures in the USA. While hiatal hernia or intrathoracic migration of the staple line is frequently described as a chronic complication, this review article sheds light on the seldom-discussed acute presentation of this alarming complication. We present a compelling case of a young female who experienced sudden and intractable vomiting shortly after LSG. Utilizing a multidisciplinary approach, upper gastrointestinal imaging (UGI) and computed tomography (CT) scans unequivocally confirmed incarcerated intrathoracic migration of the gastric sleeve, necessitating immediate surgical intervention. Radiologists must be equipped with the knowledge to recognize subtle yet crucial imaging findings from UGI and CT scans to ensure timely intervention, thus mitigating the risks associated with this underreported acute complication of LSG and ultimately improving patient outcomes and safety.

Supramolecular Engineering of Alkylated, Fluorinated, and Mixed Amphiphiles.

The rational design of perfluorinated amphiphiles to control the supramolecular aggregation in an aqueous medium is still a key challenge for the engineering of supramolecular architectures. Here, the synthesis and physical properties of six novel non-ionic amphiphiles are presented. The effect of mixed alkylated and perfluorinated segments in a single amphiphile is also studied and compared with only alkylated and perfluorinated units. To explore their morphological behavior in an aqueous medium, dynamic light scattering (DLS) and cryogenic transmission electron microscopy/electron microscopy (cryo-TEM/EM) measurements are used. The assembly mechanisms with theoretical investigations are further confirmed, using the Martini model to perform large-scale coarse-grained molecular dynamics simulations. These novel synthesized amphiphiles offer a greater and more systematic understanding of how perfluorinated systems assemble in an aqueous medium and suggest new directions for rational designing of new amphiphilic systems and interpreting their assembly process.

Sustainable Plant-Based Biopolymer Membranes for PEM Fuel Cells.

Carboxycellulose nanofibers (CNFs) promise to be a sustainable and inexpensive alternative material for polymer electrolyte membranes compared to the expensive commercial Nafion membrane. However, its practical applications have been limited by its relatively low performance and reduced mechanical properties under typical operating conditions. In this study, carboxycellulose nanofibers were derived from wood pulp by TEMPO oxidation of the hydroxyl group present on the C6 position of the cellulose chain. Then, citric acid cross-linked CNF membranes were prepared by a solvent casting method to enhance performance. Results from FT-IR spectroscopy, 13C NMR spectroscopy, and XRD reveal a chemical cross-link between the citric acid and CNF, and the optimal fuel cell performance was obtained by cross-linking 70 mL of 0.20 wt % CNF suspension with 300 µL of 1.0 M citric acid solution. The membrane electrode assemblies (MEAs), operated in an oxygen atmosphere, exhibited the maximum power density of 27.7 mW cm-2 and the maximum current density of 111.8 mA cm-2 at 80 °C and 100% relative humidity (RH) for the citric acid cross-linked CNF membrane with 0.1 mg cm-2 Pt loading on the anode and cathode, which is approximately 30 times and 22 times better, respectively, than the uncross-linked CNF film. A minimum activation energy of 0.27 eV is achieved with the best-performing citric acid cross-linked CNF membrane, and a proton conductivity of 9.4 mS cm-1 is obtained at 80 °C. The surface morphology of carboxycellulose nanofibers and corresponding membranes were characterized by FIB/SEM, SEM/EDX, TEM, and AFM techniques. The effect of citric acid on the mechanical properties of the membrane was assessed by tensile strength DMA.

High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches.

Homeostasis between pro-oxidants and anti-oxidants is necessary for aerobic life, which if perturbed and shifted towards pro-oxidants results in oxidative stress. It is generally agreed that reactive oxygen species (ROS) production is accelerated with mountainous elevation, which may play a role in spawning serious health crisis. Exposure to increasing terrestrial altitude leads to a reduction in ambient O2 availability in cells producing a series of hypoxic oxidative stress reactions and altering the redox balance in humans. Enormous literature on redox signaling drove research activity towards understanding the role of oxidative stress under normal and challenging conditions like high-altitude hypoxia which grounds for disturbed redox signaling. Excessive ROS production and accumulation of free radicals in cells and tissues can cause various pulmonary, cardiovascular, and metabolic pathophysiological conditions. In order to counteract this oxidative stress and maintain the balance of pro-oxidants and anti-oxidants, an anti-oxidant system exists in the human body, which, however, gets surpassed by elevated ROS levels, but can be strengthened through the use of anti-oxidant supplements. Such cumulative studies of fundamentals on a global concept like oxidative stress and role of anti-oxidants can act as a foundation to further smoothen for researchers to study over health, disease, and other pathophysiological conditions. This review highlights the interconnection between high altitude and oxidative stress and the role of anti-oxidants to protect cells from oxidative damages and to lower the risk of altitude-associated sickness.

Regioselective synthesis of arylsulfonyl heterocycles from bromoallyl sulfones via intramolecular Heck coupling reaction.

Indoles, benzofurans and benzosultams endowed with arylsulfonyl groups were prepared in two steps from 2-bromoallyl sulfones. ortho-Halosulfonamides and ortho-iodophenol reacted with 2-bromoallyl sulfones in the presence of cesium carbonate to furnish products resulting from a formal vinylic substitution reaction. Palladium-catalyzed intramolecular Heck reaction of these adducts furnished sulfonylated indoles, benzosultams and benzofurans. Isomerization of the double bond participating in the Heck reaction under basic conditions led to the formation of two isomeric products in two cases. Conditions for selectively accessing each of the regioisomeric indoles were developed.

Facile synthesis of biarylmethanes and tetrasubstituted arenes via a base-mediated [3 + 3] benzannulation reaction of Morita-Baylis-Hillman adducts and unsaturated sulfones.

A facile DBU-mediated [3 + 3] benzannulation reaction of 1,3-bis-sulfonyl propenes and Morita-Baylis-Hillman (MBH) bromides is described. The benzannulation reaction afforded bis-sulfonyl biarylmethanes/arenes with complete regioselectivity. The products may be converted readily into corresponding benzophenones via site-selective benzylic oxidation.

Fluorescent Polymer-Single-Walled Carbon Nanotube Complexes with Charged and Noncharged Dendronized Perylene Bisimides for Bioimaging Studies.

Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water-soluble, fluorescent, cytocompatible polymer-single-walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer-wrapped SWNTs toward surfactant-solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer-SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies.

Immune-mediated neurological manifestations of dengue virus- a study of clinico-investigational variability, predictors of neuraxial involvement, and outcome with the role of immunomodulation.

INTRODUCTION: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic. MATERIALS AND METHODS: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Laboratory as well as clinicoradiological data, the predictors of outcome, and the role of immunomodulation in determining the final result were analyzed. RESULTS: Out of the 1627 confirmed dengue cases, 14.6% developed neurological complications and only 4.86% cases had IMNC. Among the IMNC seen, the majority of the patients had the onset of their manifestations in the subacute (7-30 days) latency period; however, there was no mortality seen. We found Miller Fisher syndrome (MFS), limbic encephalitis, and immune-mediated cerebellar demyelination (IMCD) as the new findings in the IMNC spectrum. Patients with DF were more prone to developing brachial plexus neuritis and polyneuritis cranialis, whereas those patients with a severe syndrome were more commonly associated with Guillain-Barre syndrome (GBS). Significant (P < 0.001) predictors of central nervous system involvement were anemia, an elevated hematocrit, and the presence of DSS, whereas patients with a higher mean body temperature, DF, and elevated hematocrit were more prone to developing peripheral nervous system manifestations. The platelets counts and the hemoglobin levels had a negative correlation whereas the hematocrit value, the mean body temperature, and the alanine aminotransferase levels had a moderately significant positive correlation for the development of IMNC. The immunomodulatory therapy (IMT), if initiated after fever abatement led to a significant clinically favorable outcome at 3 months, especially in patients with GBS, polyneuritis cranialis, and brachial plexus neuritis. CONCLUSION: The spectrum of IMNC is vast and may include MFS, limbic encephalitis and IMCD. Early initiation of IMT, in the presence of significant predictors, may reduce the IMNC-related morbidity.

A Simple Approach to Prepare Carboxycellulose Nanofibers from Untreated Biomass.

A simple approach was developed to prepare carboxycellulose nanofibers directly from untreated biomass using nitric acid or nitric acid-sodium nitrite mixtures. Experiments indicated that this approach greatly reduced the need for multichemicals, and offered significant benefits in lowering the consumption of water and electric energy, when compared with conventional multiple-step processes at bench scale (e.g., TEMPO oxidation). Additionally, the effluent produced by this approach could be efficaciously neutralized using base to produce nitrogen-rich salts as fertilizers. TEM measurements of resulting nanofibers from different biomasses, possessed dimensions in the range of 190-370 and 4-5 nm, having PDI = 0.29-0.38. These nanofibers exhibited lower crystallinity than untreated jute fibers as determined by TEM diffraction, WAXD and 13C CPMAS NMR (e.g., WAXD crystallinity index was ∼35% for nanofibers vs 62% for jute). Nanofibers with low crystallinity were found to be effective for removal of heavy metal ions for drinking water purification.

Acetamide Derivatives of Chromen-2-ones as Potent Cholinesterase Inhibitors.

Alzheimer's disease (AD), a neurodegenerative disorder, is a serious medical issue worldwide with drastic social consequences. Inhibition of cholinesterase is one of the rational and effective approaches to retard the symptoms of AD and, hence, consistent efforts are being made to develop efficient anti-cholinesterase agents. In pursuit of this, a series of 19 acetamide derivatives of chromen-2-ones were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential. All the synthesized compounds exhibited significant anti-AChE and anti-BChE activity, with IC50 values in the range of 0.24-10.19 µM and 0.64-30.08 µM, respectively, using donepezil hydrochloride as the standard. Out of 19 compounds screened, 3 compounds, viz. 22, 40, and 43, caused 50% inhibition of AChE at 0.24, 0.25, and 0.25 µM, respectively. A kinetic study revealed them to be mixed-type inhibitors, binding with both the CAS and PAS sites of AChE. The above-selected compounds were found to be effective inhibitors of AChE-induced and self-mediated Aß1-42 aggregation. ADMET predictions demonstrated that these compounds may possess suitable blood-brain barrier (BBB) permeability. Hemolytic assay results revealed that these compounds did not lyse human RBCs up to a thousand times of their IC50 value. MTT assays performed for the shortlisted compounds showed them to be negligibly toxic after 24 h of treatment with the SH-SY5Y neuroblastoma cells. These results provide insights for further optimization of the scaffolds for designing the next generation of compounds as lead cholinesterase inhibitors.

Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives.

In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin-2(1H)-one derivative, exhibited an IC50 value comparable to that of the drug imatinib against c-Src kinase, and another compound (14) containing a 2-((4-methyl-2-oxo-2H-chromen-6-yl)oxy)acetamide demonstrated an IC50 value of 8.39 µM. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single-crystal X-ray diffraction technique. These results may serve as a gateway for developing novel next-generation kinase inhibitors.

Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: applications and future perspectives.

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz."lipases" in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc.

Mirror Aneurysm with Right Frontal ICH in a Patient with Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders that occur owing to the abnormalities in type 1 collagen, and is characterized by increased bone fragility and other extraskeletal manifestations. OI may be associated with vascular complications such as aortic and cervical artery dissection, carotid cavernous fistula, and coronary artery aneurysms but unlike other connective tissue diseases, the cerebrovascular system is less frequently involved. We report rare case of 50 year female patient who was diagnosed with OI following right frontal haemorrhage secondary to a ruptured middle cerebral artery mirror aneurysm.

Antimicrobial Efficacy of Synthetic Pyranochromenones and (Coumarinyloxy)acetamides.

Four (1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N,N,N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)decan-1-aminium bromide (1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls.

Gold-Catalyzed Cyclization Processes: Pivotal Avenues for Organic Synthesis.

Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium-sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo-, regio-, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry.

Chair-like pulses in an all-normal dispersion Ytterbium-doped mode-locked fiber laser.

We report, for what we believe is the first time, generation of stable chair-like pulses (a pulse shape with an initial long flat portion followed by a short high peak power portion resembling the shape of a chair) by mode locking of a Ytterbium (Yb)-doped fiber laser. Chair-like pulse shapes are achieved by implementing dual saturable absorbers, one based on a nonlinear optical loop mirror (NOLM) and the other based on nonlinear polarization rotation (NPR) inside the cavity. The transmission characteristics of the NOLM-NPR pair leading to the formation of chair-like pulses are numerically investigated. We also report the amplification characteristics of chair-like pulses in an external multistage Yb-doped fiber amplifier setup at different repetition rates of the pulse train. It was found that the chair-like pulses are suitable for amplification, and more than 10 W of average power at 460 kHz repetition rate have been obtained at total pump power of ∼20 W coupled to the power amplifier. At a lower repetition rate (115 kHz), ∼8 W of average power were obtained corresponding to ∼70 µJ of pulse energy with negligible contribution from amplified spontaneous emission or stimulated Raman scattering. We believe that such an oscillator-amplifier system could serve as an attractive tool for micromachining applications.

Chemo-Enzymatic Synthesis of Oligoglycerol Derivatives.

A cleaner and greener method has been developed and used to synthesize 14 different functionalized oligomer derivatives of glycerol in moderate 29%-39% yields over three steps. After successive regioselective enzymatic acylation of the primary hydroxyl groups, etherification or esterification of the secondary hydroxyl groups and chemoselective enzymatic saponification, the target compounds can efficiently be used as versatile building blocks in organic and supramolecular chemistry.

Structure-activity relationship studies of 4-methylcoumarin derivatives as anticancer agents.

CONTEXT: Cancer is a leading cause of death worldwide and novel chemotherapeutic agents with better efficacy and safety profiles are much needed. Coumarins are natural polyphenolic compounds with important pharmacological activities, which are present in many dietary plants and herbal remedies. OBJECTIVES: The objective of this study is to investigate natural and synthetic coumarin derivatives with considerable anticancer capacity against three human cancer cell lines. MATERIALS AND METHODS: We synthesized 27 coumarin derivatives (mostly having 4-methyl moiety) and examined their cytotoxic effect on three human cancer cell lines, K562 (chronic myelogenous leukemia), LS180 (colon adenocarcinoma), and MCF-7 (breast adenocarcinoma) by MTT reduction assay. Screened compounds included 7-hydroxy-4-methylcoumarins (7-HMCs), 7-acetoxy-4-methylcoumarins (7-AMCs), and different dihydroxy-4-methylcoumarin (DHMC) and diacetoxy-4-methylcoumarin (DAMC) derivatives. Some compounds with methoxy, amine, and bromine substitutions were also examined. RESULTS: 7,8-DHMCs bearing alkyl groups at C3 position were the most effective subgroup, and of which, the most potent is compound 11, with an n-decyl chain at C3, which had IC50 values of 42.4, 25.2, and 25.1 µM against K562, LS180, and MCF-7 cells, respectively. The second most active subgroup was 7,8-DAMCs containing ethoxycarbonylmethyl and ethoxycarbonylethyl moieties at C3 position. Compound 27 (6-bromo-4-bromomethyl-7-hydroxycoumarin), the only derivative containing bromine also showed reasonable cytotoxic activities (IC50 range: 32.7-45.8 µM). DISCUSSION AND CONCLUSION: This structure-activity relationship (SAR) study of 4-methylcoumarins shows that further investigation of these derivatives may lead to the discovery of novel anticancer agents.

Is single-4-ring the most basic but elusive secondary building unit that transforms to larger structures in zinc phosphate chemistry?

Haloaryl phosphates (X-dippH2, X = Cl, Br, I) react with zinc acetate in the presence of collidine or 2-aminopyridine (2-apy) to yield zinc phosphate clusters [Zn(X-dipp)(collidine)]4 (X = Cl (1), Br (2), I (3)) and [Zn(X-dipp)(2-apy)]4·2MeOH (X = Cl (4), Br (5), I (6)), respectively. Single-crystal X-ray diffraction studies reveal that collidine and 2-apy capped zinc phosphates 1-6 exist as discrete tetrameric zinc phosphate molecules, exhibiting a cubane-shaped D4R core. In contrast, when the same reaction has been carried out in the presence of 4-cyanopyridine (4-CNpy), polymeric zinc phosphates {[Zn4(X-dipp)4(4-CNpy)2(MeOH)2]·2H2O}n (X = Cl (7), Br (8), I (9)) have been isolated. Compounds 7-9 are square-wave-shaped, one-dimensional polymers composed of fused S4R repeating units. The common structural motif found both in D4R cubanes 1-6 and polymers 7-9 is the S4R building block, which presumably undergoes further fusion because of the coordinative unsaturation at zinc and the simultaneous presence of free P═O. The closed shell cubanes 1-6 are obviously formed by a face-to-face dimerization involving two S4R units in which the two P═O groups are in cis-configuration. On the other hand, the one-dimensional (1-D) square-wave polymers 7-9 are formed from a face-to-face association of S4R building units in which the two P═O groups are in a trans-configuration. In order to stabilize these elusive S4R zinc phosphates, the reaction between Cl-dippH2 and zinc acetate was carried out in the presence of excess imidazole as an ancillary ligand (1:1:4), although only an imidazole decorated cubane cluster [Zn(Cl-dipp)(imz)]4.2MeOH (10) was isolated. The chelating N,N'-donor 1,10-phenanthroline ligand was used to eventually isolate cyclic S4R phosphate [Zn(µ2-Cl-dipp)(1,10-phen)(OH2)]2·MeOH·H2O (11). The change of Zn(2+) source to zinc nitrate and the phosphate source to 2,6-dimethylphenyl phosphate (dmppH2) led to the isolation of another polymeric phosphate [Zn(dmpp)(MeOH)]n (12), with a zigzag backbone, formed through an edge-to-edge to polymerization of S4R building units with P═O groups in trans-configuration. The isolation of four different structural types of zinc phosphates A-D in the present study can be rationalized in terms of fusion of S4R rings in a variety of ways to either produce discrete clusters or 1-D polymers.