Co-Catalyst-Free Chemical Fixation of CO2 into Cyclic Carbonates by using Metal-Organic Frameworks as Efficient Heterogeneous Catalysts.

The concentration of carbon dioxide (CO2 ) in the atmosphere is increasing at an alarming rate resulting in undesirable environmental issues. To mitigate this growing concentration of CO2 , selective carbon capture and storage/sequestration (CCS) are being investigated intensively. However, CCS technology is considered as an expensive and energy-intensive process. In this context, selective carbon capture and utilization (CCU) as a C1 feedstock to synthesize value-added chemicals and fuels is a promising step towards lowering the concentration of the atmospheric CO2 and for the production of high-value chemicals. Towards this direction, several strategies have been developed to convert CO2 , a Greenhouse gas (GHG) into useful chemicals by forming C-N, C-O, C-C, and C-H bonds. Among the various CO2 functionalization processes known, the cycloaddition of CO2 to epoxides has gained considerable interest owing to its 100% atom-economic nature producing cyclic carbonates or polycarbonates in high yield and selectivity. Among the various classes of catalysts studied for cycloaddition of CO2 to cyclic carbonates, porous metal-organic frameworks (MOFs) have gained a special interest due to their modular nature facilitating the introduction of a high density of Lewis acidic (LA) and CO2 -philic Lewis basic (LB) functionalities. However, most of the MOF-based catalysts reported for cycloaddition of CO2 to respective cyclic carbonates in high yields require additional co-catalyst, say tetra-n-butylammonium bromide (TBAB). On the contrary, the co-catalyst-free conversion of CO2 using rationally designed MOFs composed of both LA and LB sites is relatively less studied. In this review, we provide a comprehensive account of the research progress in the design of MOF based catalysts for environment-friendly, co-catalyst-free fixation of CO2 into cyclic carbonates.

Rational Design of a 3D MnII -Metal-Organic Framework Based on a Nonmetallated Porphyrin Linker for Selective Capture of CO2 and One-Pot Synthesis of Styrene Carbonates.

A 3D MnII -porphyrin metal-organic framework (MOF), [{Mn2 (TCPP)⋅2H2 O}⋅DMF]n (MOF1) (TCPP=5,10,15,20-tetrakis(4-benzoate)porphyrin), was constructed; it exhibits an interesting 3D framework structure with two types of 1D channels of dimensions of 3.94×8.37 Å2 and 4.66×4.93 Å2 running along the crystallographic a axis. Owing to the presence of a nonmetallated porphyrin cavity, MOF1 exhibits selective storage of CO2 with an isosteric heat of adsorption value of 32.1 kJ mol-1 , which is further supported by theoretical calculations with the calculated binding energy (BE) of 29.78 kJ mol-1 . Interestingly, the nonmetallated nature of the porphyrin ligand was exploited for implantation of coordinatively unsaturated FeIII ions to generate a FeIII @MOF1 framework, which acts as an efficient recyclable catalyst for the oxidation of styrenes to the corresponding epoxides in the presence of PhIO as an oxidant at room temperature. Moreover, the one-pot synthesis of styrene carbonates from styrenes and CO2 was also achieved using FeIII @MOF1 as a catalyst. The rational design of a porous MnII -porphyrin MOF for the selective capture of CO2 and the one-pot synthesis of styrene carbonates at mild conditions is reported.

Ruthenium(ii) arene NSAID complexes: inhibition of cyclooxygenase and antiproliferative activity against cancer cell lines.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of molecules which have been found to be active against cancer cells with chemopreventive properties by targeting cyclooxygenase (COX-1 and COX-2) and lipoxygenase (LOX), commonly upregulated (particularly COX-2) in malignant tumors. Arene ruthenium(ii) complexes with a pseudo-octahedral coordination environment containing different ancillary ligands have shown remarkable activity against primary and metastatic tumors as reported earlier. This work describes the synthesis of four novel ruthenium(ii)-arene complexes viz. [Ru(η6-p-cymene)(nap)Cl] 1 [Hnap = naproxen or (S)-2-(6-methoxy-2-naphthyl)propionic acid], [Ru(η6-p-cymene)(diclo)Cl] 2 [Hdiclo = diclofenac or 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, [Ru(η6-p-cymene)(ibu)Cl] 3 [Hibu = ibuprofen or 2-(4-isobutylphenyl)propanoic acid] and [Ru(η6-p-cymene)(asp)Cl] 4 [Hasp = aspirin or 2-acetoxy benzoic acid] using different NSAIDs as chelating ligands. Complexes 1-3 have shown promising antiproliferative activity against three different cell lines with GI50 (concentration of drug causing 50% inhibition of cell growth) values comparable to adriamycin. At the concentration of 50 µM, complex 3 is more effective in the inhibition of cyclooxygenase and lipooxygenase enzymes, followed by complex 2 and complex 1 in comparison to their respective free NSAID ligands indicating a possible correlation between the inhibition of COX and/or LOX and anticancer properties. Molecular docking studies with COX-2 reveal that complexes 1 and 2 having naproxen and diclofenac ligands exhibit stronger interactions with COX-2 than their respective free NSAIDs and these results are in good agreement with their relative experimentally observed COX inhibition as well as anti-proliferative activities.

Rational Design of a Bifunctional, Two-Fold Interpenetrated ZnII -Metal-Organic Framework for Selective Adsorption of CO2 and Efficient Aqueous Phase Sensing of 2,4,6-Trinitrophenol.

A bifunctional, microporous ZnII metal-organic framework, [Zn2 (NH2 BDC)2 (dpNDI)]n (MOF1) (where, NH2 BDC=2-aminoterephthalic acid, dpNDI=N,N'-di(4-pyridyl)-1,4,5,8-naphthalenediimide) has been synthesized solvothermally. MOF1 shows an interesting two-fold interpenetrated, 3D pillar-layered framework structure composed of two types of 1D channels with dimensions of approximately 2.99×3.58 Šand 4.58×5.38 Šdecorated with pendent -NH2 groups. Owing to the presence of a basic functionalized pore surface, MOF1 exhibits selective adsorption of CO2 with high value of heat of adsorption (Qst =46.5 kJ mol-1 ) which is further supported by theoretically calculated binding energy of 48.4 kJ mol-1 . Interestingly, the value of Qst observed for MOF1 is about 10 kJ mol-1 higher than that of analogues MOF with the benzene-1,4-dicarboxylic acid (BDC) ligand, which establishes the critical role of the -NH2 group for CO2 capture. Moreover, MOF1 exhibits highly selective and sensitive sensing of the nitroaromatic compound (NAC), 2,4,6-trinitrophenol (TNP) over other competing NACs through a luminescence quenching mechanism. The observed selectivity for TNP over other nitrophenols has been correlated to stronger hydrogen bonding interaction of TNP with the basic -NH2 group of MOF1, which is revealed from DFT calculations. To the best of our knowledge, MOF1 is the first example of an interpenetrated ZnII -MOF exhibiting selective adsorption of CO2 as well as efficient aqueous-phase sensing of TNP; investigated through combined experimental and theoretical studies.

Fine tuning through valence bond tautomerization of ancillary ligands in ruthenium(ii) arene complexes for better anticancer activity and enzyme inhibition properties.

Four new ruthenium arene PTA type complexes have been synthesized using substituted picolinamide derivatives as ancillary ligands and characterized by spectroscopic methods. In one of the complexes, the ancillary ligand has shown an unprecedented valence-bond tautomerization in the presence of an ammonium salt to act as a polar neutral donor ligand making the ligand more prone towards substitution. The same compound has shown remarkable antiproliferative activity against three cancer cell lines with GI50 values comparable to Adriamycin, a known therapeutic drug. Along with this it also strongly inhibits the action of thioredoxin reductase, which might be a probable reason for the enhanced proliferative action of the valence-bond tautomerized compound.

Construction of 3-Fold-Interpenetrated Three-Dimensional Metal-Organic Frameworks of Nickel(II) for Highly Efficient Capture and Conversion of Carbon Dioxide.

A series of three new isostructural metal-organic frameworks (MOFs) of nickel(II), [{Ni(muco)(bpa)(2H2O)}·2H2O] (1), [{Ni(muco)(bpe)(2H2O)}·2.5H2O] (2), and [{Ni(muco)(azopy)(2H2O)}·2H2O] (3) [where muco = trans,trans-muconate dianion, bpa = 1,2-bis(4-pyridyl)ethane, bpe = 1,2-bis(4-pyridyl)ethylene, and azopy = 4,4'-bis(azobipyridine)], have been synthesized and characterized by single-crystal X-ray diffraction analysis and other physicochemical methods. Compounds 1-3 exhibit an interesting 3-fold-interpenetrated three-dimensional pillar-layered framework structure constituted of 4-coordinating (4-c) NiII nodes with {66}-neb net topology. Remarkably, in spite of 3-fold interpenetration, the structures possess one-dimensional channels with dimensions of ∼8.05 × 5.25 Å2. Gas (N2, Ar, H2, and CO2) adsorption studies of compounds 2 and 3 revealed selective adsorption properties for CO2 over other gases. In all three structures, the 4-c NiII node has two coordinated H2O molecules that can be reversibly removed by high-temperature treatment to generate a dehydrated framework composed of highly unsaturated, Lewis acidic NiII ions. Further, the activated compounds of 1-3 act as efficient recyclable catalysts for heterogeneous cycloaddition of CO2 with styrene oxide, resulting in cyclic carbonate with high conversion and selectivity. Interestingly, the cycloaddition reactions of CO2 with bulky epoxides show a decrease in the activity with an increase in the alkyl chain length of the substrate due to confinement of the pore size of the MOF. The high catalytic efficiency and size-dependent selectivity for smaller epoxides show the potential utility of 1 as a promising heterogeneous catalyst for the cycloaddition of CO2. Furthermore, the catalyst can be easily separated and reused for several cycles without significant reduction in the catalytic activity as well as structural rigidity. Compounds 1-3 represent rare examples of interpenetrated MOFs exhibiting selective storage and conversion of CO2 at mild conditions.

Studies on Antifungal Potential, Primary Characterization and Mode of Action of a De Novo Cytoplasmic Protein (EAF) from Human Commensal Escherichia coli Against Aspergillus spp.

A de novo protein named as EAF (Escherichia antifungal protein) from the cytoplasmic pool of an Escherichia coli strain (MTCC 1652), has been purified to homogeneity using anion exchange (Q-XL Sepharose) and cation exchange (SP-Sepharose) chromatography. The MIC (minimum inhibitory concentration) values of purified protein against A. fumigatus (the major pathogenic species) were found to be comparable with standard drugs i.e. 3.90 µg/ml, 3.90 µg/ml and 1.25 µg/disc via microbroth dilution assay (MDA), percentage spore germination inhibition (PSGI) and disc diffusion assay (DDA) respectively. Toxicity results confirmed that it causes no haemolysis against human RBCs upto a concentration of 1000.0 µg/ml as compared to Amphotericin B (conventional antifungal drug) that causes hundred percent haemolysis at a concentration of 37.50 µg/ml only.The purified protein demonstrated a molecular mass of 28 kDa on SDS-PAGE which was further authenticated by MALDI-TOF. Proteomic and bioinformatics studies deciphered its significant homology (72 %) with chain A-D-ribose binding protein (cluster 2 sugar binding periplasmic proteins; sequence homologues of transcription regulatory proteins) from E. coli. Single dimensional page analysis of A. fumigatusproteins with due effect of EAF (at MIC50) revealed the inhibition of two major proteins; a heat shock protein 70-Hsp70 (68 kDa); having role in protein folding and functioning andphenylanalyl-t RNA synthetase PodG subunit protein (74 kDa); involved in growth polarity in fungi. Scanning electron microscopic studies depicted homologous results. We suggest that EAF most likely belongs to a new group of proteins with potent antifungal characteristics, negligible toxicity and targeting vital proteins of fungal metabolism.

Isolation and biological evaluation of novel Tetracosahexaene hexamethyl, an acyclic triterpenoids derivatives and antioxidant from Justicia adhatoda.

Forty five extracts fraction of nine selected Indian medicinal plants, based on their use in traditional systems of medicine were analyzed for their antioxidant potential. All the extracts were investigated for phenol content value calculated in Gallic acid equivalents (% of GAE) and antioxidant potential. Moreover, total phenolic content (% dw equivalents to gallic acid) of all plant extracts were found in the range of 3.04 to 24.03, which correlated with antioxidant activity. The findings indicated a promising antioxidant activity of crude extracts fractions of three plants (Justicia adhatoda, Capparis aphylla and Aegle marmelos) and required the further exploration for their effective utilization. Results indicated that petroleum ether fraction of J. adhatoda out of three plants also possesses the admirable antioxidant abilities with high total phenolic content. Following, in vitro antioxidant activity-guided phytochemical separation procedures, twelve fractions of petroleum ether extract of J. adhatoda were isolated by silica gel column chromatography. One fraction (Rf value: 0.725) showed the noticeable antioxidant activity with ascorbic acid standard in hydroxyl radical scavenging assays. The molecular structures elucidations of purified antioxidant compound were carried out using spectroscopic studies ((1)H NMR, (13)C NMR and MS). This compound was reported from this species for the first time. The results imply that the J. adhatoda might be a potential source of natural antioxidants and 2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl is an antioxidant ingredient in J. adhatoda.

An anti-Aspergillus protein from Escherichia coli DH5α: putative inhibitor of siderophore biosynthesis in Aspergillus fumigatus.

An antifungal protein designated as anti-Aspergillus protein (AAP), produced by Escherichia coli DH5α, was purified and characterised. It exhibited a molecular weight of 60 kDa on Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis and depicted 99% purity on ultra performance liquid chromatography. The purified protein manifested antimycotic potential against pathogenic isolates of Aspergillus spp., depicting a minimum inhibitory concentration in the range 15.62-31.25 µg ml(-1) and 5.0-10.0 µg per disc, using microbroth dilution, spore germination inhibition and disc diffusion assays respectively. In vitro toxicity tests demonstrated that it showed no toxicity against human erythrocytes at doses up to 1000 µg ml(-1) . Matrix-assisted laser desorption ionisation-Time-of-flight analysis of trypsin-digested peptides of purified protein and subsequent Mascot search revealed that several peptides of AAP have identity with bacterial siderophore biosynthetic protein, i.e. non-ribosomal peptide synthetase enzyme, involved in critical step of fungal siderophore biosynthesis. Siderophore-based inhibition was further corroborated by Chrome azurol S assay. Hence, the antagonistic effect might be the result of impediment in siderophore-mediated iron uptake and transport process which may cause critical consequences on Aspergillus growth and virulence.

Genomics of Chronic Obstructive Pulmonary Disease (COPD); Exploring the SNPs of Protease-Antiprotease Pathway.

The COPD has been an important respiratory condition that affects people worldwide and its incidence has been alarming. The increasing incidence of this disorder has been attributed to global industrialization and environmental pollution. Although the exposures to environmental pollutants and smoking have been important triggers, the genetic component of individuals has been shown to be important for development and progression of COPD. Recent literature reported that protease-antiprotease imbalance to be important in etiopathogenesis of COPD. The enzymes namely neutrophil elastase and matrix metalloprotienases are considered to be foremost proteolytic molecules released by neutrophils and macrophages during inflammatory events in COPD. Normally, the lungs remain protected from the destructive effect of these two antiproteases by α1-antitrypsin (α1AT) and tissue inhibitors of metalloproteinases (TIMPs) respectively. In this review, we are trying to highlight the work by various research groups in exploring the SNPs of various genes of inflammatory pathways and the protease-antiprotease pathway, which may have some degree of association with COPD.

Safety and efficacy of green foliage in the treatment of fungal infections and associated clinical conditions.

Forty five crude extracts of nine selected medicinal plants, based on their use in respiratory and other disorders in traditional systems of medicine were analyzed for their potential activity against three pathogenic species of Aspergillus. The presence of phenols, tannins, flavanoids, terpenoid, steroids, alkaloids and saponins in the different extracts was established. The crude extracts were examined for antifungal activity in concentration ranging from 5000.0 to 19.53 µg/ml using microbroth dilution assay in which twenty two extracts exhibited the anti-Aspergilli activity. The petroleum ether extract of Justicia adhatoda and water extract of Commelina bengalensis exhibited the maximum activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Their in vitro minimum inhibitory concentrations (MICs) were found to be 156.0-312.0 µg/ml by microbroth dilution and spore germination inhibition assays. In disc diffusion assay, at concentration of 10 µg/disc of some crude extracts showed significant activity against Aspergilli. The toxicity (in vitro and in vivo) of bio-active fractions was evaluated, in which the extracts isolated from J. adhatoda were found to be non-toxic. Gas chromatography-mass spectrometry (GCMS) studies were performed for various extracts (petroleum ether, chloroform and acetone) of J. adhatoda which resulted in the identification of several bioactive compounds. The antifungal activity along with acute toxicity, cyto-toxicity as well as genotoxicity of extract fractions from J. adhatoda justifies the use of such screening in the expedition for new drugs.

Advancement in infection control of opportunistic pathogen (Aspergillus spp.): adjunctive agents.

There is continuous emergence of resistant strains which leads to urgent need to discover new antifungal agents. The investigation of adjunctive agents for antifungal activity might help to optimize the therapy for Invasive Aspergillosis (IA). The chelating agents Ethylenediamine Tetraacetic Acid (EDTA) & Disodium salt of EDTA (DiEDTA) as adjunct to antifungal drugs have been investigated against 8 pathogenic isolates of Aspergillus spp. The MIC (Minimum Inhibitory Concentration) found by DDA (Disc Diffusion Assay) is 7.50-15.0 µg/disc; by MDA (Microbroth Dilution Assay) is 30.0-49.13 µg/ml & SGIA (Spore germination Inhibition Assay) is 30.0-49.13 µg/ml. Moreover, these agents did not show any toxicity up to a concentration of 312.5 µg/ml. The antifungal activity is also confirmed by another method i.e time kill curve analysis. While these agents were ten times less active than gold standard drug (Amphotericin B; AmpB) but eight times less toxic than AmpB. This leads to preliminary investigation of in vitro combination of chelating agents with antifungal drugs (Polyenes & Azoles) by DDA. These combinations showed a significant increase in zone of inhibition in contrast to single drug used. This preliminary work with chelating agents suggest that EDTA as an enhancing agent with antifungal properties in combination with antifungal drugs can be used in pharmaceutical preparations. Further investigation is in progress.

Investigations towards new antidiabetic drugs from fungal endophytes associated with Salvadora oleoides Decne.

The nature has provided abundant natural resources which can be explored for their medicinal uses. The present study was undertaken to investigate the antidiabetic and hypolipidemic activity of various extract's fractions obtained from mycelia of seventeen endophytic fungi in different solvents (methanol, acetone and aqueous) isolated from Salvadora oleoides Decne (Salvadoraceae) in glucose loaded fasting and alloxan induced diabetic Wistar albino rats. Only four extracts namely; unidentified fungus (aqueous), Aspergillus sp.JPY2 (methanol), Aspergillus sp.JPY1 (methanol) and Phoma sp. (acetone) significantly reduced blood glucose levels as revealed by glucose tolerance test. It has been observed that in alloxan induced diabetic rats, the maximum reduction in blood glucose level was after 5 hours in the acute treatment experiment and on14th day in sub acute treatment at a dose of 250mg/kg of body weight (P<0.05). The reduction in blood glucose in long term treatment experiment was ranged from 11.3% to 28.04%, whereas standard drug tolbutamide reduced the blood glucose level up to 40%. In long term treatment, unidentified fungus (aqueous) extract showed significant improvement in parameters like body weight and lipid profile of alloxan induced diabetic rats. The gas chromatography mass spectrometer (GCMS) analysis of bioactive fraction (aqueous) of unidentified fungus and methanolic extract fraction of Aspergillus sp.JPY1 revealed that the main constituents were 2, 6-di-tert-butyl-p-cresol and Phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl respectively. The results have also suggested that the above four bioactive fractions have good margin of safety and did not show any lethal effects on the animals up to the doses of 1000mg/kg b.w. along with safe doses up to 500 µg/ ml to human erythrocytes.

Analysis toward innovative herbal antibacterial and antifungal drugs.

The antimicrobial activities of four medicinal plants Argemona mexicana, Achyranthes aspera, Catharanthus roseus, and Syzygium cumini were evaluated against Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae, Proteus vulgaris, Bacillus subtilis, Salmonella typhi and three Aspergillus species. Extracts from Achyranthes aspera and Catharanthus roseus showed the highest antimicrobial potential (MIC 0.375-0.750 mg/ml) while extract from Argemona mexicana and Syzygium cumini, showed less activity. In disc diffusion assay, only eight out of twenty extracts showed antimicrobial activity at a concentration of 25.0 µg/ disc. The GCMS investigation reveals the existence of 2-bornanone; 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl) ester; hexadecanoic acid, methyl ester and hexatriacontane in water extract fraction of C. roseus. The present research article provides a review of some medicinal plants incorporating antimicrobial drugs, together with recent advances in emerging therapeutics in clinical development and related patents for exploitation of herbal medicine.

Invasive aspergillosis: adjunctive combination therapy.

Invasive aspergillosis remains a serious opportunistic fungal infection particularly in patients with a reduced immune defense such as those with hematological malignancies or transplant recipients. The mortality of invasive infections due to Aspergillus spp. is still high. The main reasons for this are the difficulty in diagnosing of these infections and the limited efficacy of antifungal agents. There is no optimal therapy for invasive aspergillosis, and therefore many clinicians have attempted to utilize a combination approach to improve outcomes. The current antifungal classes of drugs targeting the cell wall and cell membrane may need adjunctive agents focused on separate cellular pathways that can be used in combination therapy to maximize the efficacy, a valuable alternative to the monotherapy. The endeavor of this article is to review the literature on combination therapy by using adjunctive agents against Aspergillus spp and assess its eventual usability in the treatment of invasive aspergillosis.