A Highly Chemically Robust 3D Interpenetrated MOF Heterogeneous Catalyst for the Synthesis of Hantzsch 1,4-Dihydropyridines and Drug Molecules.

Metal-organic frameworks (MOFs) have attracted immense attention as efficient heterogeneous catalysts over other solid catalysts, however, their chemical environment instability often limits their catalytic potential. Herein, utilizing a flexible unexplored tetra-acid ligand and employing the mixed ligand approach, a 3D interpenetrated robust framework is strategically developed, IITKGP-51 (IITKGP stands for Indian Institute of Technology Kharagpur), which retained its crystallinity over a wide range of pH solution (4-12). Having ample open metal sites (OMSs), IITKGP-51 is explored as a heterogeneous catalyst in one-pot Hantzsch condensation reaction, with low catalyst loading for a broad range of substrates. The synthesis of drug molecules remains one of the most significant and emergent areas of organic and medicinal chemistry. Considering such practical utility, biologically important Nemadipine B and Nifedipine drug molecules (calcium channel protein inhibitor) are synthesized for the first time by using this catalyst and fully characterized via SC-XRD and other spectroscopic methods. This report inaugurates the usage of a MOF material as a catalyst for the synthesis of drug molecules.

Mechanistical Insights into the Ultrasensitive Detection of Radioactive and Chemotoxic UO22+ Ions by a Porous Anionic Co-Metal-Organic Framework.

Development of a simple, cost-efficient, and portable UO22+ sensory probe with high selectivity and sensitivity is highly desirable in the context of monitoring radioactive contaminants. Herein, we report a luminescent Co-based metal-organic framework (MOF), {[Me2NH2]0.5[Co(DATRz)0.5(NH2BDC)]·xG}n (1), equipped with abundant amino functionalities for the selective detection of uranyl cations. The ionic structure consists of two types of channels decorated with plentiful Lewis basic amino moieties, which trigger a stronger acid-base interaction with the diffused cationic units and thus can selectively quench the fluorescence intensity in the presence of other interfering ions. Furthermore, the limit of detection for selective UO22+ sensing was achieved to be as low as 0.13 µM (30.94 ppb) with rapid responsiveness and multiple recyclabilities, demonstrating its excellent efficacy. Density functional theory (DFT) calculations further unraveled the preferred binding sites of the UO22+ ions in the tubular channel of the MOF structure. Orbital hybridization between NH2BDC/DATRz and UO22+ together with its significantly large electron-accepting ability is identified as responsible for the luminescence quenching. More importantly, the prepared 1@PVDF {poly(vinylidene difluoride)} mixed-matrix membrane (MMM) displayed good fluorescence activity comparable to 1, which is of great significance for their practical employment as MOF-based luminosensors in real-world sensing application.

A Water-Stable Cationic SIFSIX MOF for Luminescent Probing of Cr2 O7 2- via Single-Crystal to Single-Crystal Transformation.

The sensing and monitoring of toxic oxo-anion contaminants in water are of significant importance to biological and environmental systems. A rare hydro-stable SIFSIX metal-organic framework, SiF6 @MOF-1, {[Cu(L)2 (H2 O)2 ]·(SiF6 )(H2 O)}n , with exchangeable SiF6 2- anion in its pore is strategically designed and synthesized, exhibiting selective detection of toxic Cr2 O7 2- oxo-anion in an aqueous medium having high sensitivity, selectivity, and recyclability through fluorescence quenching phenomena. More importantly, the recognition and ion exchange mechanism is unveiled through the rarely explored single-crystal-to-single crystal (SC-SC) fashion with well-resolved structures. A thorough SC-SC study with interfering anions (Cl- , F- , I- , NO3 - , HCO3 - , SO4 2- , SCN- , IO3 - ) revealed no such transformations to take place, as per line with quenching studies. Density functional theory calculations revealed that despite a lesser binding affinity, Cr2 O7 2- shows strong orbital mixing and large driving forces for electron transfer than SiF6 2- , and thus enlightens the fluorescence quenching mechanism. This work inaugurates the usage of a SIFSIX MOF toward sensing application domain under aqueous medium where hydrolytic stability is a prime concern for their plausible implementation as sensor materials.

pH-Stable Zn(II) Coordination Polymer as a Multiresponsive Turn-On and Turn-Off Fluorescent Sensor for Aqueous Medium Detection of Al(III) and Cr(VI) Oxo-Anions.

Nowadays, coordination polymers (CPs) are promising candidates as sensory materials for their high sensitivity, improved selectivity, fast responsive nature, as well as good recyclability. However, poor chemical stability often makes their practical usage limited. Herein, employing a mixed ligand approach, we constructed a chemically robust CP, {[Zn2L2(DPA)2]·3H2O}n (IITKGP-70, IITKGP stands for the Indian Institute of Technology Kharagpur), which exhibited excellent framework robustness not only in water but also over a broad range of pH solutions (pH = 3-11). The developed framework displayed high selectivity and sensitivity for the detection of trivalent Al3+ ions and toxic hexavalent Cr(VI)-oxo anions in an aqueous medium. The developed framework exhibited an aqueous medium Al3+ turn-on phenomenon with a limit of detection (LOD) value of 1.29 µM, whereas a turn-off effect was observed for toxic oxo-anions (Cr2O72- and CrO42-) having LOD values of 0.27 and 0.71 µM, respectively. Both turn-on and turn-off mechanisms are speculated via spectroscopic methods coupled with several ex situ studies. Such a multiresponsive nature (both turn-on and turn-off) for aqueous medium detection of targeted cations and anions simultaneously in a single platform coupled with high robustness, ease of scalability, recyclability, and fast-responsive nature makes IITKGP-70 highly fascinating as a sensory material for real-world applications.

Highly Robust Metal-Organic Framework for Efficiently Catalyzing Knoevenagel Condensation and the Strecker Reaction under Solvent-Free Conditions.

Metal-organic frameworks (MOFs) have been recognized as one of the most promising porous materials and offer great opportunities for the rational design of new catalytic solids having great structural diversity and functional tunability. Despite numerous inherent merits, their chemical environment instability limits their practical usage and demands further exploration. Herein, by employing the mixed-ligand approach, we have designed and developed a robust 3D Co-MOF, [Co2(µ2-O)(TDC)2(L)(H2O)2]·2DMF (H2TDC = 2,5-thiophenedicarboxylic acid, L = 3,3'-azobispyridine), IITKGP-50 (IITKGP stands for the Indian Institute of Technology Kharagpur), which exhibited excellent framework robustness not only in water but also in a wide range of aqueous pH solutions (pH = 2-12). Taking advantage of superior framework robustness and the presence of high-density open metal sites, IITKGP-50 was further explored in catalyzing the two-component Knoevenagel condensation reaction and three-component Strecker reactions. Moreover, to verify the size selectivity of IITKGP-50, smaller to bulkier substrates in comparison with the MOF's pore cavity (8.1 × 5.6 Å2) were employed, in which relatively lesser conversions for the sterically bulkier aldehyde derivatives confirmed that the catalytic cycle occurs inside the pore cavity. The easy scalability, lower catalyst loading compared to that of benchmark MOFs, magnificent conversion rate over a wide range of substrates, and excellent recyclability without significant performance loss made IITKGP-50 a promising heterogeneous catalyst candidate.

A Chemically Robust 2D Ni-MOF as an Efficient Heterogeneous Catalyst for One-Pot Synthesis of Therapeutic and Bioactive 2-Amino-3-Cyano-4H-Pyran Derivatives.

Despite possessing numerous catalytic advantages of MOFs, developing 2D frameworks having excellent chemical stability along with new catalytic properties, remains a grand challenge. Herein, by employing a mixed ligand synthetic approach, we have constructed a 2D Ni-MOF, IITKGP-52, which exhibits excellent framework robustness in open air, water, as well as over a wide range of pH solutions (2-12). Benefitting from its robustness and abundant Lewis acidic open metal sites, IITKGP-52 is explored in catalyzing the heterogeneous three-component condensation reaction for the tandem synthesis of bioactive 2-amino-3-cyano-4H-pyran derivatives with low catalytic loading, greater compatibility for a wide range of substrates, excellent recyclability and superior catalytic efficiency than the previously employed homo and heterogeneous systems. IITKGP-52 inaugurates the employment of MOF-based catalysts for one-pot synthesis of therapeutic and bioactive 2-amino-3-cyano-4H-pyran derivatives.

Pd(II)-Catalyzed Oxidative Naphthylation of 2-Pyridone through N-H/C-H Activation Using Diarylacetylene as an Uncommon Arylating Agent.

A Pd(II)-catalyzed straightforward oxidative naphthylation of unmasked 2-pyridone derivatives is described using a twofold internal alkyne as a coupling partner. The reaction proceeds through N-H/C-H activation to provide polyarylated N-naphthyl 2-pyridones. An unusual oxidative annulation at the arene C-H bond of the diarylalkyne leads to the formation of polyarylated N-naphthyl 2-pyridones, where the 2-pyridone-attached phenyl ring of the naphthyl ring is polyaryl-substituted. Mechanistic studies and DFT calculations suggest a plausible mechanism based on N-H/C-H activation. The N-naphthyl 2-pyridone derivatives were studied to explore encouraging photophysical properties.

Correction: Anti-Inflammatory Activity of Odina wodier Roxb, an Indian Folk Remedy, through Inhibition of Toll-Like Receptor 4 Signaling Pathway.

[This corrects the article DOI: 10.1371/journal.pone.0104939.].

Photoluminescence and photo-induced conductivity in 2D siloxene nanosheet for optoelectronic applications.

Semiconducting 2D siloxene nanosheets of thickness 1.7 nm and band gap of 2.54 eV are synthesized using simple chemical route. Strong photoluminescence is observed in the as-synthesized nanosheets due to presence of oxygen atoms. The photoluminescence behaviour of siloxene nanosheets is investigated by controlling temperature, excitation and pH of the solution to understand the optical response and stability of the material. The as-synthesized sample heated with temperature 200 °C shows a blue shift of 90 nm compared to the sample synthesized at room temperature. The low temperature luminescence measurements of as-synthesized samples dried at different temperatures viz. 27, 100 and 200 °C. It is seen that the luminescence intensity is increasing with decreasing temperature for the sample dried at room temperature. However, after heating the sample at 100 °C, the luminescence intensity is not only increased but also red-shifted up to 52 nm. The photocurrent has been measured for the device structure of ITO/PEDOT: PSS/Siloxene/Al with different film thicknesses to optimize the photocurrent and the maximum percentage change in photo power gain. The maximum photopower gain of 2693% is observed for the film thickness of 600 nm.

White light emitting lanthanide based carbon quantum dots as toxic Cr (VI) and pH sensor.

Although, great attention is paid to synthesize fluorescent carbon quantum dots (CQDs) for versatile applications, the field remains still attractive to achieve white light using these nano materials. In the present work, CQDs are synthesized from citric acid and lanthanide ions viz. Europium (Eu) and Terbium (Tb) are doped in CQD moiety to explore superior optical response for multifunctional applications. By proper tuning of excitation wavelength, perfect white light with Commission Internationale de l'Elcairage (CIE) index (0.345, 0.344) is obtained using these Europium Terbium co-doped CQDs (Eu-Tb-CQD). The observed photoluminescence of white light emitting lanthanide based CQD is pH dependent and will be used as a visual pH sensor. These luminescent Eu and Tb co-doped CQDs are also very useful to detect toxic Cr (VI) with excellent selectivity and sensitivity as compared to pure CQDs. It shows high quenching efficiency (∼95%) in presence of only 160 µM Cr(VI). The selectivity and lower detection limit are also obtained as ∼80% and 0.175 µM respectively.

Carbamazepine in Treatment of Visual Hallucinations: A Case of Chronic Hallucinatory Psychosis.

Visual hallucinations are commonly present in various neurological and psychiatric conditions such as schizophrenia and other hallucinatory psychosis. Current conceptualization of hallucinations assume pattern completion model of thalamus to be responsible for the origin of this type of the perceptual abnormality and proposes that central inhibition of such circuits may treat hallucinations. We present a case of chronic hallucinatory psychosis with significantly distressing visual hallucinations, resistant to antipsychotics, which successfully responded to carbamazepine. This case illustrates the novel use of an antiepileptic in the treatment of resistant visual hallucinations. Targeted therapy of this kind can be considered in the future, although more evidence is required in this field.

Risperidone-induced mania: An emergent complication of treatment.

The occurrence of manic/hypomanic switch in patients being treated with risperidone has been reported by various authors, and they have described a variety of strategies for their management. In this report, we describe two cases of induction of elevated mood symptoms in patients treated with risperidone. We propose that the emergence of these symptoms may be a complication of treatment with this drug in susceptible individuals, of which the clinicians should be aware, mainly in those diagnosed with schizophrenia and bipolar disorder. We then discuss a few findings that might be useful in the management of such cases. We thereby also propose a mechanism for such an induction.

Anti-inflammatory activity of Odina wodier Roxb, an Indian folk remedy, through inhibition of toll-like receptor 4 signaling pathway.

Inflammation is part of self-limiting non-specific immune response, which occurs during bodily injury. In some disorders the inflammatory process becomes continuous, leading to the development of chronic inflammatory diseases including cardiovascular diseases, diabetes, cancer etc. Several Indian tribes used the bark of Odina wodier (OWB) for treating inflammatory disorders. Thus, we have evaluated the immunotherapeutic potential of OWB methanol extract and its major constituent chlorogenic acid (CA), using three popular in vivo antiinflammatory models: Carrageenan- and Dextran-induced paw edema, Cotton pellet granuloma, and Acetic acid-induced vascular permeability. To elucidate the possible anti-inflammatory mechanism of action we determine the level of major inflammatory mediators (NO, iNOS, COX-2-dependent prostaglandin E2 or PGE2), and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-12). Further, we determine the toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88), c-Jun N-terminal kinases (JNK), nuclear factor kappa-B cells (NF-κB), and NF-kB inhibitor alpha (IK-Bα) by protein and mRNA expression, and Western blot analysis in drug treated LPS-induced murine macrophage model. Moreover, we determined the acute and sub-acute toxicity of OWB extract in BALB/c mice. Our study demonstrated a significant anti-inflammatory activity of OWB extract and CA along with the inhibition of TNF-α, IL-1ß, IL-6 and IL-12 expressions. Further, the expression of TLR4, NF-κBp65, MyD88, iNOS and COX-2 molecules were reduced in drug-treated groups, but not in the LPS-stimulated untreated or control groups, Thus, our results collectively indicated that the OWB extract and CA can efficiently inhibit inflammation through the down regulation of TLR4/MyD88/NF-kB signaling pathway.

A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the viral immediate early transcriptional events.

In our continued quest for identifying novel molecules from ethnomedicinal source we have isolated an alkaloid 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole, also known as Harmaline (HM), from an ethnomedicinal herb Ophiorrhiza nicobarica. The compound exhibited a potent anti-HSV-1 activity against both wild type and clinical isolates of HSV-1. Further we demonstrated that HM did not interfere in viral entry but the recruitment of lysine-specific demethylase-1 (LSD1) and the binding of immediate-early (IE) complex on ICP0 promoter. This leads to the suppression of viral IE gene synthesis and thereby the reduced expression of ICP4 and ICP27. Moreover, HM at its virucidal concentration is nontoxic and reduced virus yields in cutaneously infected Balb/C mice. Thus, the interference in the binding of IE complex, a decisive factor for HSV lytic cycle or latency by HM reveals an interesting target for developing non-nucleotide antiherpetic agent with different mode of action than Acyclovir.

Acute Delirium due to Parenteral Tramadol.

Tramadol is a widely used medication by physicians and is held to be a safe analgesic. It has been claimed to be helpful in the elderly and hepatic and renally compromised subjects. We would like to report a case of delirium in a middle-aged female with acute pain abdomen on tramadol while being treated in the surgical unit. The patient developed alteration in the level of consciousness and cognitive deficits following injectable dose of tramadol. She was diagnosed as a case of tramadol-induced delirium. The patient improved spontaneously after stoppage of tramadol injection. The probable mechanism for development of tramadol-induced delirium is discussed along with clinical implications.

Evaluation of the wound healing activity of Shorea robusta, an Indian ethnomedicine, and its isolated constituent(s) in topical formulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of Indian ethnomedicinal plant Shorea robusta is traditionally used for several ailments including wounds and burn by different tribal groups, since ages. Here we have validated, for the first time, the effectiveness and the possible mechanism of action of young leaf extracts of Shorea robusta, used by two distinct tribes of India, and its isolated compounds as a topical formulation in three wound models in rats. MATERIALS AND METHODS: Bioactivity-guided study of the active extract resulted in the isolation of two known compounds. The prepared ointment containing extracts (2.5 and 5%, w/w), fractions (5% w/w) and isolated compounds (0.25% w/w) were evaluated on excision, incision and dead space wound models in rats by the rate of wound closure, period of epithelialisation, tensile strength, granulation tissue weight, hydroxyproline content and histopathology. RESULTS: The animals treated with the extracts and fractions (5%) showed significant reduction in wound area 96.55 and 96.41% with faster epithelialisation (17.50 and 17.86), while the isolated compounds bergenin and ursolic acid heal the wound faster, but complete epithelialisation with 100% wound contraction was evident with 5% povidone-iodine group on 18th post-wounding day. Moreover, the tensile strength of incision wound, granuloma tissue weight, and hydroxyproline content was significantly increased in both the extract and compound(s) treated animals. Furthermore, the tissue histology of animals treated with the isolated compound(s) showed complete epithelialisation with increased collagenation, similar to povidone-iodine group. CONCLUSION: Thus, our results validated the traditional use of Shorea robusta young leaves in wound management.

An indole alkaloid from a tribal folklore inhibits immediate early event in HSV-2 infected cells with therapeutic efficacy in vaginally infected mice.

Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the management of HSV-2 infections.

Life-threatening thrombocytosis following GCSF treatment in a case of clozapine-induced agranulocytosis.

Clozapine was introduced in European market in 1972 as an effective treatment for schizophrenia without extrapyramidal side effects. Within a short while, the clozapine story virtually came to a halt following detection of life-threatening neutropenia and agranulocytosis. Judicial use of granulocyte colony stimulating factor (GCSF) can be life saving with infrequent side effects in these cases. Here we are presenting a case of clozapine induced agranulocytosis managed with GCSF but had transient but life-threatening thrombocytosis, a very uncommon complication of GCSF therapy. Expression of GCSF receptors on the surface of megakaryocytic lineage is thought to be the cause of this unusual phenomenon.