Recent Development in Fluorescent Probes for Copper Ion Detection.

Copper is the third most common heavy metal and an indispensable component of life. Variations of body copper levels, both structural and cellular, are related to a number of disorders; consequently, the pathophysiological importance of copper ions demands the development of sensitivity and selection for detecting these organisms in biological systems. In recent years, the area of fluorescent sensors for detecting copper metal ions has seen revolutionary advances. Consequently, closely related fields have raised awareness of several diseases linked to copper fluctuations. Further developments in this field of analysis could pave the way for new and innovative treatments to combat these diseases. This review reports on recent progress in the advancement of three fields of fluorescent probes; chemodosimeters, near IR fluorescent probes, and ratiometric fluorescent probes. Methods used to develop these fluorescent probes and the mechanisms that govern their reaction to specific analytes and their applications in studying biological systems, are also given.

An Earth-abundant cobalt based photocatalyst: visible light induced direct (het)arene C-H arylation and CO2 capture.

In this work, we have reported a noble metal free heterogeneous photocatalyst to carry out direct (het)arene C-H arylation and solvent-free CO2 capture via single-electron transfer processes at room temperature and under pressure. The catalytic system comprises a cobalt(III) complex grafted over the silica coated magnetic support for the efficient recovery of the photocatalytic moiety without hampering its light-harvesting capability. The novel Earth-abundant cobalt(III) based photocatalyst possesses various fascinating properties such as high surface area to volume ratios, large pore volume, crystalline behaviour, high metal loading, excellent stability and reusability. The general efficacy of the highly abundant and low-cost cobalt based heterogeneous nanocatalyst was checked for the selective conversion of aryldiazonium salts into synthetically and pharmaceutically significant biaryl motifs under ambient conditions upon irradiation with visible light. The highly efficient photocatalytic conversion of carbon dioxide (CO2) to a value-added chemical was accomplished under mild reaction conditions with high selectivity, showing the added benefit of operational simplicity.

Fabrication, functionalization and advanced applications of magnetic hollow materials in confined catalysis and environmental remediation.

Magnetic hollow-structured functional hybrid materials with unique architectures and preeminent properties have always been an area of extensive research. They represent a subtle collaboration of hollow architecture, mesoporous nanostructure and magnetic character. Owing to the merits of a large void space, low density, high specific surface area, well-defined active sites and facile magnetic recovery, these materials present promising application projections in numerous fields, such as drug delivery, adsorption, storage, catalysis and many others. In this review, recent progress in the design, synthesis, functionalization and applications of magnetic hollow-meso/nanostructured materials are discussed. The first part of the review has been dedicated to the preparation and functionalization of the materials. The synthetic protocols have been broadly classified into template-assisted and template-free methods and major trends in their synthesis have been elaborated in detail. Furthermore, the benefits and drawbacks of each method are compared. The later part summarizes the application aspects of confined catalysis in organic transformations and environmental remediation such as degradation of organic pollutants, dyes and antibiotics and adsorption of heavy metal ions. Finally, an outlook of future directions in this research field is highlighted.

Chemistry and Pharmacology of Natural Catechins from Camellia sinensis as Anti-MRSA Agents.

Tea, a worldwide popular beverage rich in polyphenols, contributes to the prevention of many diseases and thus is beneficial to human health. Tea is a product through processing the fresh leaves picked from the plant Camellia sinensis (C. sinensis, genus Camellia section Thea). To date, systematic studies have been conducted on the phytochemicals from more than 20 tea varieties and related tea products, resulting in the structural determination of over 400 constituents viz. different types of polyphenols, purines, and their derivatives, mono to tetra-terpenoids, and minor other phytomolecules. These various tea phytochemicals contribute to the anti-oxidative effects, anti-diabetes, anti-inflammation, anti-cancer, blood lipid reduction, neuroprotection, anti-Alzheimer's disease, hepatoprotection, and anti-microbial activities, etc. Staphylococcus aureus (S. aureus), the significant human pathogens, could cause nosocomial and community-acquired infections, which is also responsible for various infectious diseases from mild to severe life-threatening conditions, such as bacteremia (bloodstream infection), endocarditis (heart valves infection), pneumonia, and meningitis (brain infection), leading to 2% clinical disease in of all patient admissions. The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of ß-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.

An Efficient and Sustainable Approach to Decarboxylative Cross-Coupling Using Silica Coated Magnetic Copper Nanocatalyst for the Synthesis of Internal Alkynes.

A highly efficient magnetically separable copper nanocatalyst has been developed for decarboxylative cross-coupling reaction for the alkynylation of haloarenes using alkynoic acid as a reaction partner. The chemical nature, morphology, size, and magnetic properties of the prepared nanocatalyst were studied by SEM, TEM, EDS, FT-IR, VSM, and ICP techniques. Remarkably, this catalyst represents the first successful copper based heterogeneous system for this type of coupling that provides a low-cost, stable, and environmentally friendly magnetically recoverable entity that can be re-used for seven consecutive runs without appreciable loss in its catalytic performance.

Synthesis, molecular modelling studies of indolyl chalcone derivatives and their antimalarial activity evaluation.

Twenty one chalcone derivatives were synthesized using Claisen-Schmidt condensation, their antimalarial activity against Plasmodium falciparum was determined and quantitative structure-activity relationship (QSAR) was developed. Condensation of substituted acetophenones with various aromatic aldehydes at room temperature gave chalcones in 75-96% yield. Chalcones are secondary metabolites of terrestrial plants, precursors for the biosynthesis of flavonoids and exhibit various biological activities. Antiplasmodial IC50 (half-maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was Trans-3-(1H-indol-3-yl)-1-(2'-hydroxyphenyl)-2-propen-1-one (1b) with IC50 of 2.1 µM/L. Molecular mechanism was explored through in silico docking & ADMET studies for the active compounds.

Detection and quantification of flavoalkaloids in different tea cultivars and during tea processing using UPLC-TOF-MS/MS.

Flavoalkaloids have been found from tea. However, there is limited information about their content in different teas. Herein, 51 tea samples were screened for flavoalkaloid content. Twelve teas with relatively higher contents of flavoalkaloids were further quantified by UPLC-TOF-MS/MS. The cultivars Yiwu and Bulangshan had the highest levels, with total flavoalkaloid contents of 3063 and 2727 µg g-1, respectively. Each of the six flavoalkaloids were at levels > 198 µg g-1 in these cultivars. Of the flavoalkaloids, etc-pyrrolidinone A had the highest content in the teas, reaching 835 µg g-1 in Yiwu. The content of the flavoalkaloids varied among tea cultivars and with processing procedures, particularly heating. The potential of using flavoalkaloids to discriminate grades of Keemun black tea was studied and discussed. The teas identified in this work with high levels of flavoalkaloids can be used in the future to study the mechanisms by which flavoalkaloids are synthesized in tea.

A high-density SNP-based linkage map using genotyping-by-sequencing and its utilization for improved genome assembly of chickpea (Cicer arietinum L.).

Genotyping-by-sequencing (GBS) allows rapid identification of markers for use in development of linkage maps, which expedite efficient breeding programs. In the present study, we have utilized GBS approach to identify and genotype single-nucleotide polymorphism (SNP) markers in an inter-specific RIL population of Cicer arietinum L. X C. reticulatum. A total of 141,639 raw SNPs were identified using the TASSEL-GBS pipeline. After stringent filtering, 8208 candidate SNPs were identified of which ~ 37% were localized in the intragenic regions followed by genic regions (~ 30%) and intergenic regions (~ 27%). We then utilized 6920 stringent selected SNPs from present study and 6714 SNPs and microsatellite markers available from previous studies for construction of linkage map. The resulting high-density linkage map comprising of eight linkage groups contained 13,590 markers which spanned 1299.14 cM of map length with an average marker density of 0.095 cM. Further, the derived linkage map was used to improve the available assembly of desi chickpea genome by anchoring 443 previously unplaced scaffolds onto eight linkage groups. The present efforts have refined anchoring of the desi chickpea genome assembly to 55.57% of the ~ 520 Mb of assembled desi genome. To the best of our knowledge, the linkage map generated in the present study represents one of the most dense linkage map developed for the crop till date. It will serve as a valuable resource for fine mapping and positional cloning of important quantitative trait loci (QTLs) associated with agronomical traits and also for anchoring and ordering of future genome sequence assemblies.

Novel Cinnamoylated Flavoalkaloids Identified in Tea with Acetylcholinesterase Inhibition Effect.

3-O-Cinnamoylepicatechin (1) was synthesized along with four flavoalkaloids, (-)-6-(5‴S)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (2), (-)-6-(5‴R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (3), (-)-8-(5‴S)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (4), and (-)-8-(5‴R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (5) via esterification of epicatechin followed by phenolic Mannich reaction of 1 with theanine in the presence of heat. The new compounds 1-5 were detected in leaves of three tea cultivars, Fuding-Dabai, Huangjingui, and Zimudan with the help of ultra-performance liquid chromatography hyphenated with a photodiode array detector and electrospray ionization high-resolution mass spectrometry (UPLC-PDA-ESI-HRMS), suggesting that they are naturally occurring in tea leaves. The structures of the novel natural products were characterized by one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) and mass spectroscopy. Compounds 1-5 were then evaluated for their acetylcholinesterase (AChE) inhibitory effect (IC50 = 0.12-1.02 µM). The availability of the synthesized epicatechin derivatives 1-5 via a synthetic route enabled the first unequivocal identification of these derivatives as tea secondary metabolites and made it possible to determine their content in the tea material as well as the diverse bioactivities.

A template free protocol for fabrication of a Ni(ii)-loaded magnetically separable nanoreactor scaffold for confined synthesis of unsymmetrical diaryl sulfides in water.

In the present report, an environmentally benign magnetically recoverable nickel(ii)-based nanoreactor as a heterogeneous catalyst has been developed via a template free approach. The catalytic performance of the synthesized catalyst is assessed in the confined oxidative coupling of arenethiols with arylhydrazines to form unsymmetrical diaryl sulfides under aerobic conditions. The salient features of our protocol include oxidant- and ligand-free conditions, use of water as a green solvent, room temperature and formation of nitrogen and water as the only by-products. Moreover, a broad range of functional groups are tolerated well and provide the corresponding diaryl sulfides in moderate to good yields. Moreover, the heterogeneous nature of the catalyst permits facile magnetic recovery and reusability for up to seven runs, making the present protocol highly desirable from industrial and environmental standpoints.

Silica-Coated Magnetic-Nanoparticle-Supported DABCO-Derived Acidic Ionic Liquid for the Efficient Synthesis of Bioactive 3,3-Di(indolyl)indolin-2-ones.

In this work, biologically significant 3,3-di(indolyl)indolin-2-ones have been synthesized using a silica-coated magnetic-nanoparticle-supported 1,4-diazabicyclo[2.2.2]octane (DABCO)-derived and acid-functionalized ionic liquid as the catalytic entity. The fabricated nanocomposite catalyzes the pseudo-three-component reaction of isatins and indoles explicitly via hydrogen-bonding interactions between substrates and the catalyst. The nanocatalytic system utilizes water as the green reaction medium to obtain a library of indolinones in good to excellent yields under mild reaction conditions. Besides, the catalyst could be easily recovered from the reaction mixture through simple external magnetic forces, which enables excellent recyclability of the catalyst for successive runs without appreciable loss in catalytic activity. Hence, the outcomes of the present methodology make the nanocatalyst a potential candidate for the development of green and sustainable chemical processes.

Cross-dehydrogenative C(sp3)-C(sp3) coupling via C-H activation using magnetically retrievable ruthenium-based photoredox nanocatalyst under aerobic conditions.

In the present work, we report the fabrication of a highly versatile ruthenium-based magnetically recoverable photoredox nanocatalyst with a large surface area. This visible light harvesting nanocatalyst was effectively used for cross-dehydrogenative coupling via C-H activation between tertiary amines and various carbon nucleophiles with high regioselectivity to afford the C-C coupled products in good to excellent yield using air as an oxidant under ambient conditions. The Ru-based catalyst was found to be a potential candidate from economical and environmental perspectives due to its magnetic recoverability and reusability.

A novel bi-functional chalcone inhibits multi-drug resistant Staphylococcus aureus and potentiates the activity of fluoroquinolones.

Staphylococcus aureus is the leading cause of bacteraemia and the dwindling supply of effective antibacterials has exacerbated the problem of managing infections caused by this bacterium. Isoliquiritigenin (ISL) is a plant flavonoid that displays therapeutic potential against S. aureus. The present study identified a novel mannich base derivatives of ISL, IMRG4, active against Vancomycin intermediate S. aureus (VISA). IMRG4 damages the bacterial membranes causing membrane depolarization and permeabilization, as determined by loss of salt tolerance, flow cytometric analysis, propidium idodie and fluorescent microscopy. It reduces the intracellular invasion of HEK-293 cells by S. aureus and decreases the staphylococcal load in different organs of infected mice models. In addition to anti-staphylococcal activity, IMRG4 inhibits the multidrug efflux pump, NorA, which was determined by molecular docking and EtBr efflux assays. In combination, IMRG4 significantly reduces the MIC of norfloxacin for clinical strains of S. aureus including VISA. Development of resistance against IMRG4 alone and in combination with norfloxacin was low and IMRG4 prolongs the post-antibiotic effect of norfloxacin. These virtues combined with the low toxicity of IMRG4, assessed by MTT assay and haemolysis, makes it an ideal candidate to enter drug development pipeline against S. aureus.

An efficient copper-based magnetic nanocatalyst for the fixation of carbon dioxide at atmospheric pressure.

In the last few decades, the emission of carbon dioxide (CO2) in the environment has caused havoc across the globe. One of the most promising strategies for fixation of CO2 is the cycloaddition reaction between epoxides and CO2 to produce cyclic carbonates. For the first time, we have fabricated copper-based magnetic nanocatalyst and have applied for the CO2 fixation. The prepared catalyst was thoroughly characterized using various techniques including XRD, FT-IR, TEM, FE-SEM, XPS, VSM, ICP-OES and elemental mapping. The reactions proceeded at atmospheric pressure, relatively lower temperature, short reaction time, solvent- less and organic halide free reaction conditions. Additionally, the ease of recovery through an external magnet, reusability of the catalyst and excellent yields of the obtained cyclic carbonates make the present protocol practical and sustainable.

Comparative Analysis of Fruit Metabolites and Pungency Candidate Genes Expression between Bhut Jolokia and Other Capsicum Species.

Bhut jolokia, commonly known as Ghost chili, a native Capsicum species found in North East India was recorded as the naturally occurring hottest chili in the world by the Guinness Book of World Records in 2006. Although few studies have reported variation in pungency content of this particular species, no study till date has reported detailed expression analysis of candidate genes involved in capsaicinoids (pungency) biosynthesis pathway and other fruit metabolites. Therefore, the present study was designed to evaluate the diversity of fruit morphology, fruiting habit, capsaicinoids and other metabolite contents in 136 different genotypes mainly collected from North East India. Significant intra and inter-specific variations for fruit morphological traits, fruiting habits and 65 fruit metabolites were observed in the collected Capsicum germplasm belonging to three Capsicum species i.e., Capsicum chinense (Bhut jolokia, 63 accessions), C. frutescens (17 accessions) and C. annuum (56 accessions). The pungency level, measured in Scoville Heat Unit (SHU) and antioxidant activity measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay showed maximum levels in C. chinense accessions followed by C. frutescens accessions, while C. annuum accessions showed the lowest value for both the traits. The number of different fruit metabolites detected did not vary significantly among the different species but the metabolite such as benzoic acid hydroxyl esters identified in large percentage in majority of C. annuum genotypes was totally absent in the C. chinense genotypes and sparingly present in few genotypes of C. frutescens. Significant correlations were observed between fruit metabolites capsaicin, dihydrocapsaicin, hexadecanoic acid, cyclopentane, α-tocopherol and antioxidant activity. Furthermore, comparative expression analysis (through qRT-PCR) of candidate genes involved in capsaicinoid biosynthesis pathway revealed many fold higher expression of majority of the genes in C. chinense compared to C. frutescens and C. annuum suggesting that the possible reason for extremely high pungency might be due to the higher level of candidate gene(s) expression although nucleotide variation in pungency related genes may also be involved in imparting variations in level of pungency.

Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.

A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 µM for 48 h whereas DHA has IC50 value of 2 µM at same time period. The most potent compounds 8 with IC50 = 0.3 µM (at par with doxorubicin (IC50 = 0.3 µM)) and 15 with IC50 = 0.4 µM, of the series, six and three times active than DHA (with IC50 = 2 µM) respectively were selected for further mechanistic work in human leukemia HL-60 cells.

Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin Isolated from Glycyrrhiza glabra Against Methicillin-Resistant Staphylococcus aureus (MRSA).

Isoliquiritigenin (ISL) and liquiritigenin (LTG) are structurally related flavonoids found in a variety of plants. Discovery of novel antimicrobial combinations for combating methicillin-resistant Staphylococcus aureus (MRSA) infections is of vital importance in the post-antibiotic era. The present study was taken to explore the in vitro and in vivo combination effect of LTG and ISL with ß-lactam antibiotics (penicillin, ampicillin and oxacillin) against mec A-containing strains of MRSA. Minimum inhibitory concentration (MIC) of both LTG and ISL exhibited significant anti-MRSA activity (50-100 µg/mL) against clinical isolates of MRSA. The result of in vitro combination study showed that ISL significantly reduced MIC of ß-lactam antibiotics up to 16-folds [∑ fractional inhibitory concentration (FIC) 0.312-0.5], while LTG reduced up to 8-folds (∑FIC 0.372-0.5). Time kill kinetics at graded MIC combinations (ISL/LTG + ß-lactam) indicated 3.27-9.79-fold and 2.59-3.48-fold reduction in the growth of clinical isolates of S. aureus respectively. In S. aureus-infected Swiss albino mice model, combination of ISL with oxacillin significantly (p < 0.05, p < 0.01, p < 0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison with ISL, oxacillin alone as well as untreated control. Considering its synergistic antibacterial effect, we suggest both ISL and LTG as promising compounds for the development of novel antistaphylococcal combinations. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis of Iron Oxide Palladium Nanoparticles and Their Catalytic Applications for Direct Coupling of Acyl Chlorides with Alkynes.

A new, magnetic, silica-based, palladium nanocatalyst has been synthesized and employed for the first time in the direct coupling of acyl chlorides with terminal alkynes to prepare a variety of ynones. The synthesized nanocomposite is an excellent heterogeneous catalyst for copper-free, phosphine-free, C-C bond formation through the Sonogashira reaction under aerobic conditions at room temperature without the use of any additives and inert conditions. The synthesized catalyst has been comprehensively characterized by various techniques, such as XRD, SEM, TEM, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, FTIR spectroscopy, vibrating sample magnetometry, and atomic absorption spectroscopy. This nanocatalyst can be magnetically recovered and reused in multiple runs without any noticeable loss in catalytic activity.

High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea.

This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties.

Development and Integration of Genome-Wide Polymorphic Microsatellite Markers onto a Reference Linkage Map for Constructing a High-Density Genetic Map of Chickpea.

The identification of informative in silico polymorphic genomic and genic microsatellite markers by comparing the genome and transcriptome sequences of crop genotypes is a rapid, cost-effective and non-laborious approach for large-scale marker validation and genotyping applications, including construction of high-density genetic maps. We designed 1494 markers, including 1016 genomic and 478 transcript-derived microsatellite markers showing in-silico fragment length polymorphism between two parental genotypes (Cicer arietinum ICC4958 and C. reticulatum PI489777) of an inter-specific reference mapping population. High amplification efficiency (87%), experimental validation success rate (81%) and polymorphic potential (55%) of these microsatellite markers suggest their effective use in various applications of chickpea genetics and breeding. Intra-specific polymorphic potential (48%) detected by microsatellite markers in 22 desi and kabuli chickpea genotypes was lower than inter-specific polymorphic potential (59%). An advanced, high-density, integrated and inter-specific chickpea genetic map (ICC4958 x PI489777) having 1697 map positions spanning 1061.16 cM with an average inter-marker distance of 0.625 cM was constructed by assigning 634 novel informative transcript-derived and genomic microsatellite markers on eight linkage groups (LGs) of our prior documented, 1063 marker-based genetic map. The constructed genome map identified 88, including four major (7-23 cM) longest high-resolution genomic regions on LGs 3, 5 and 8, where the maximum number of novel genomic and genic microsatellite markers were specifically clustered within 1 cM genetic distance. It was for the first time in chickpea that in silico FLP analysis at genome-wide level was carried out and such a large number of microsatellite markers were identified, experimentally validated and further used in genetic mapping. To best of our knowledge, in the presently constructed genetic map, we mapped highest number of new sequence-based robust microsatellite markers (634) which is an advancement over the previously documented (~300 markers) inter-specific genetic maps. This advanced high-density map will serve as a foundation for large-scale marker validation and genotyping applications, including identification and targeted mapping of trait-specific genes/QTLs (quantitative trait loci) with sub-optimal use of resources and labour in chickpea.