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A series of manganese(II) and oxomanganese(IV) complexes supported by neutral, pentadentate ligands with varied equatorial ligand-field strength (N3pyQ, N2py2I, and N4pyMe2) were synthesized and then characterized using structural and spectroscopic methods. On the basis of electronic absorption spectroscopy, the [MnIV(O)(N4pyMe2)]2+complex has the weakest equatorial ligand field among a set of similar MnIV-oxo species. In contrast, [MnIV(O)(N2py2I)]2+shows the strongest equatorial ligand-field strength for this same series. We examined the influence of these changes in electronic structure on the reactivity of the oxomanganese(IV) complexes using hydrocarbons and thioanisole as substrates. The [MnIV(O)(N3pyQ)]2+complex, which contains one quinoline and three pyridine donors in the equatorial plane, ranks among the fastest MnIV-oxo complexes in C–H bond and thioanisole oxidation. While a weak equatorial ligand field has been associated with high reactivity, the [MnIV(O)(N4pyMe2)]2+complex is only a modest oxidant. Buried volume plots suggest that steric factors dampen the reactivity of this complex. Trends in reactivity were examined using density functional theory (DFT)-computed bond dissociation free energies (BDFEs) of the MnIIIO–H and MnIV═ O bonds. We observe an excellent correlation between MnIV═O BDFEs and rates of thioanisole oxidation, but more scatter is observed between hydrocarbon oxidation rates and the MnIIIO–H BDFEs.

Four new pentadentate N5-donor ligands, [N-(1-methyl-2-imidazolyl)methyl-N-(2-pyridyl)-methyl-N-(bis-2-pyridylmethyl)-amine] (L1), [N-bis(1-methyl-2-imidazolyl)methyl-N-(bis-2-pyridylmethyl)amine] (L2), (N-(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine (L3), and N,N-bis(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)methanamine (L4), have been synthesized based on the N4Py ligand framework, where one or two pyridyl arms of the N4Py parent are replaced by (N-methyl)imidazolyl or N-(isoquinolin-3-ylmethyl) moieties. Using these four pentadentate ligands, the mononuclear complexes [FeII(CH3CN)(L1)]2+(1a), [FeII(CH3CN)(L2)]2+(2a), [FeII(CH3CN)(L3)]2+(3a), and [FeII(CH3CN)(L4)]2+(4a) have been synthesized and characterized. The half-wave potentials (E1/2) of the complexes become more positive in the order: 2a< 1a< 4a≤ 3a≤ [Fe(N4Py)(CH3CN)]2+. The order of redox potentials correlates well with the Fe–Naminedistances observed by crystallography, which are 2a> 1a≥ 4a> 3a≥ [Fe(N4Py)(CH3CN)]2+. The corresponding ferryl complexes [FeIV(O)(L1)]2+(1b), [FeIV(O)(L2)]2+(2b), [FeIV(O)(L3)]2+(3b), and [FeIV(O)(L4)]2+(4b) were prepared by the reaction of the ferrous complexes with isopropyl 2-iodoxybenzoate (IBX ester) in acetonitrile. The greenish complexes 3band 4bwere also isolated in the solid state by the reaction of the ferrous complexes in CH3CN with ceric ammonium nitrate in water. Mössbauer spectroscopy and magnetic measurements (using superconducting quantum interference device) show that the four complexes 1b, 2b, 3b, and 4bare low-spin (S= 1) FeIV═O complexes. UV/vis spectra of the four FeIV═O complexes in acetonitrile show typical long-wavelength absorptions of around 700 nm, which are expected for FeIV═O complexes with N4Py-type ligands. The wavelengths of these absorptions decrease in the following order: 721 nm (2b) > 706 nm (1b) > 696 nm (4b) > 695 nm (3b) = 695 nm ([FeIV(O) (N4Py)]2+), indicating that the replacement of the pyridyl arms with (N-methyl) imidazolyl moieties makes L1and L2exert weaker ligand fields than the parent N4Py ligand, while the ligand field strengths of L3and L4are similar to the N4Py parent despite the replacement of the pyridyl arms with N-(isoquinolin-3-ylmethyl) moieties. Consequently, complexes 1band 2btend to be less stable than the parent [FeIV(O)(N4Py)]2+complex: the half-life sequence at room temperature is 1.67 h (2b) < 16 h (1b) < 45 h (4b) < 63 h (3b) ≈ 60 h ([FeIV(O)(N4Py)]2+). Compared to the parent complex, 1band 2bexhibit enhanced reactivity in both the oxidation of thioanisole in the oxygen atom transfer (OAT) reaction and the oxygenation of C–H bonds of aromatic and aliphatic substrates, presumed to occur viaan oxygen rebound process. Furthermore, the second-order rate constants for hydrogen atom transfer (HAT) reactions affected by the ferryl complexes can be directly related to the C–H bond dissociation energies of a range of substrates that have been studied. Using either IBX ester or H2O2as an oxidant, all four new FeIIcomplexes display good performance in catalytic reactions involving both HAT and OAT reactions.

The association of microorganisms with livestock as endosymbionts, opportunists, and pathogens has been a matter of debate for a long time. Several livestock-associated bacterial and other microbial species have been identified and characterized through traditional culture-dependent genomic approaches. However, it is imperative to understand the comprehensive microbial network of domestic animals for their wellness, disease management, and disease transmission control. Since it is strenuous to provide a niche replica to any microorganisms while culturing them, thus a substantial number of microbial communities remain obscure. Metagenomics has laid out a powerful lens for gaining insight into the hidden microbial diversity by allowing the direct sequencing of the DNA isolated from any livestock sample like the gastrointestinal tract, udder, or genital system. Through metatranscriptomics and metabolomics, understanding gene expression profiles of the microorganisms and their molecular phenotype has become unchallenging. With large data sets emerging out of the genomic, metagenomic, and other meta-omics methods, several computational tools have also been developed for curation, assembly, gene prediction, and taxonomic profiling of the microorganisms. This review provides a detailed account of the beneficial and pathogenic organisms that dwell within or on farm animals. Besides, it highlights the role of meta-omics and computational tools in a comprehensive analysis of livestock-associated microorganisms.

Background: Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups. Methodology: The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. Result: Variant rs3791679 of EFEMP1was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37–1.58. Conclusion: This study identifies EFEMP1as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.

Drinking water distribution system water quality can be affected by chemical and microbial processes. A change in the chemical concentration of water is a result of pipe scaling and corrosion. It causes insignificant deterioration of water quality. This study determined the corrosion and scaling potential of the drinking water in the distribution networks of the water supply in Patna City, Bihar, India. For the determination of the physico-chemical parameters, 92 water samples were collected from 46 points of the distribution network. Four parameters were analysed in situ – namely, temperature, electrical conductivity, pH and total dissolved solids – and the remaining parameters – alkalinity, total hardness, calcium, magnesium, chloride, sulfate, nitrate and iron – were measured in the laboratory. Various widely used indices – namely, Langelier saturation index (LSI), Ryznar stability index (RSI), Puckorius scaling index (PSI), Larson–Skold index (LS) and aggressive index (AI) – were used to calculate corrosion and scaling potential of water samples. A result of the LSI and RSI, show that 86.96% of water samples are corrosive and only 13.04% are scaling tendency. PSI shows 30.43% of water samples are corrosive. LS shows all water samples are mildly corrosive. AI shows 71.74% of the water samples are moderately corrosive and only 28.26% of the water samples are scaling tendency.

Increasingly, people who inject drugs (PWID) infected with hepatitis C virus (HCV) are gaining access to highly effective direct-acting antiviral agents (DAAs). Although past studies examined patient experiences with interferon-based treatments, few have explored patient experiences with these new generation therapeutics. Research and real world experience indicate that many PWID can be successfully treated with the new DAAs. Yet a substantial minority fail to complete treatment or achieve only suboptimal adherence. This qualitative study examines experiences with treatment among participants in Project HERO, a large multisite trial designed to compare treatment delivery methods for DAAs. We explored treatment experiences among HERO participants, with the goal of understanding potential barriers to treatment engagement and completion.

The reactivity of six MnIV–oxo complexes in C–H bond oxidation has been examined using a combination of kinetic experiments and computational methods. Variable-temperature studies of the oxidation of 9,10-dihydroanthracene (DHA) and ethylbenzene by these MnIV–oxo complexes yielded activation parameters suitable for evaluating electronic structure computations. Complementary kinetic experiments of the oxidation of deuterated DHA provided evidence for hydrogen-atom tunneling in C–H bond oxidation for all MnIV–oxo complexes. These results are in accordance with the Bell model, where tunneling occurs near the top of the transition-state barrier. Density functional theory (DFT) and DLPNO–CCSD(T1) computations were performed for three of the six MnIV–oxo complexes to probe a previously predicted multistate reactivity model. The DFT computations predicted a thermal crossing from the 4B1ground state to a 4E state along the C–H bond oxidation reaction coordinate. DLPNO–CCSD(T1) calculations further confirm that the 4E transition state offers a lower energy barrier, reinforcing the multistate reactivity model for these complexes. We discuss how this multistate model can be reconciled with recent computations that revealed that the kinetics of C–H bond oxidation by this set of MnIV–oxo complexes can be well-predicted on the basis of the thermodynamic driving force for these reactions.

The differentiation of human stem cells into insulin secreting beta‐like cells holds great promise to treat diabetes. Current protocols drive stem cells through stages of directed differentiation and maturation and produce cells that secrete insulin in response to glucose. Further refinements are now needed to faithfully phenocopy the responses of normal beta cells. A critical factor in normal beta cell behavior is the islet microenvironment which plays a central role in beta cell survival, proliferation, gene expression and secretion. One important influence on native cell responses is the capillary basement membrane. In adult islets, each beta cell makes a point of contact with basement membrane protein secreted by vascular endothelial cells resulting in structural and functional polarization. Interaction with basement membrane proteins triggers local activation of focal adhesions, cell orientation, and targeting of insulin secretion. This study aims to identifying the role of basement membrane proteins on the structure and function of human embryonic stem cell and induced pluripotent stem cell‐derived beta cells. Here, we show that differentiated human stem cells‐derived spheroids do contain basement membrane proteins as a diffuse web‐like structure. However, the beta‐like cells within the spheroid do not polarize in response to this basement membrane. We demonstrate that 2D culture of the differentiated beta cells on to basement membrane proteins enforces cell polarity and favorably alters glucose dependent insulin secretion. Glucose stimulated insulin secretion is compromised in stem cell‐derived beta cells. In native islets, beta cell microenvironment play critical role in glucose sensing and stimulated insulin secretion. Reconstructing beta cell niche in vitro by introducing basement membrane proteins in planar culture, decreases basal insulin secretion, and enhances stimulation index in human pluripotent stem cell‐derived beta cells.

ABSTRACTOrganisations interact with each other for mutual benefits. Federation refers to one such interaction where each organisation functions independently yet is bound by contracts with others. Rural business process outsourcing (RBPO), multi-institution course management system, and video streaming services are a few examples of federations. Security of shared resources is an important concern in such scenarios. Since each organisation is independent, it is difficult to communicate the precise semantics of access control policies to other participating organisations for correct enforcement. Over the years, ontology has been employed across different domains and can be used for sharing access control semantics across organisations. In this work, we describe a network-aware digital object-based access control model (NA-DOBAM) as an extension of the popular role-based access control model to address the specific needs of security in federations. The relationship between web ontology language and NA-DOBAM model is studied. We have used an ontology-based approach for specification and implementation of NA-DOBAM in the context of RBPO where the access control policy depends on the structure of the users and objects along with the network state. We demonstrate the applicability of ontology for RBPO case studies for extracting meaningful access control information using queries as well as for enforcing access control policies including separation of duty and delegation.

Chondromyxoid fibroma (CMF) is a rare, benign, cartilaginous bone tumor that commonly affects the metaphysis of the lower-extremity long bones in young adults. Involvement of the craniofacial bones, especially the temporal bone, is exceedingly rare. We report a case of a 64-year-old man who presented with a left ear mass, but on subsequent imaging was found to have a more extensive mass centered in the temporal bone. Initial biopsy raised the concern for a low-grade chondrosarcoma. However, following surgical resection, a diagnosis of CMF was rendered. The clinical findings, radiographic features, histology, and differential diagnoses are discussed.

The oxomanganese(IV) complex [(dpaq)MnIV(O)]+-Mn+(1-Mn+, Mn+= redox-inactive metal ion, H-dpaq = 2-[bis(pyridin-2-ylmethyl)]amino-N-quinolin-8-ylacetamide), generated in the reaction of the precursor hydroxomanganese(III) complex 1with iodosylbenzene (PhIO) in the presence of redox-inactive metal triflates, has recently been reported. Herein the generation of the same oxomanganese(IV) species from 1using various combinations of protic acids and oxidants at 293 K is reported. The reaction of 1with triflic acid and the one-electron-oxidizing agent [RuIII(bpy)3]3+leads to the formation of the oxomanganese(IV) complex. The putative species has been identified as a mononuclear high-spin (S= 3/2) nonheme oxomanganese(IV) complex (1-O) on the basis of mass spectrometry, Raman spectroscopy, EPR spectroscopy, and DFT studies. The optical absorption spectrum is well reproduced by theoretical calculations on an S= 3/2 ground spin state of the complex. Isotope labeling studies confirm that the oxygen atom in the oxomanganese(IV) complex originates from the MnIII–OH precursor and not from water. A mechanistic investigation reveals an initial protonation step forming the MnIII–OH2complex, which then undergoes one-electron oxidation and subsequent deprotonations to form the oxomanganese(IV) transient, avoiding the requirements of either oxo-transfer agents or redox-inactive metal ions. The MnIV–oxo complex cleaves the C–H bonds of xanthene (k2= 5.5 M–1s–1), 9,10-DHA (k2= 3.9 M–1s–1), 1,4-CHD (k2= 0.25 M–1s–1), and fluorene (k2= 0.11 M–1s–1) at 293 K. The electrophilic character of the nonheme MnIV–oxo complex is demonstrated by a large negative ρ value of 2.5 in the oxidation of para-substituted thioanisoles. The complex emerges as the “most reactive” among the existing MnIV/V–oxo complexes bearing anionic ligands.

A mononuclear iron(II) complex [FeII(N4PyMe2)(OTf)](OTf)(1), supported by a new pentadentate ligand, bis(6-methylpyridin-2-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (N4PyMe2), has been isolated and characterized. Introduction of methyl groups in the 6-position of two pyridine rings makes the N4PyMe2a weaker field ligand compared to the parent N4Py ligand. Complex 1is high-spin in the solid state and converts to [FeII(N4PyMe2)(CH3CN)](OTf)2(1a) in acetonitrile solution. The iron(II) complex in acetonitrile displays temperature-dependent spin-crossover behavior over a wide range of temperature. In its reaction with m-CPBA or oxone in acetonitrile at −10 °C, the iron(II) complex converts to an iron(IV)-oxo species, [FeIV(O)(N4PyMe2)]2+(2). Complex 2exhibits the Mössbauer parameters δ = 0.05 mm/s and ΔEQ= 0.62 mm/s, typical of N-ligated S= 1 iron(IV)-oxo species. The iron(IV)-oxo complex has a half-life of only 14 min at 25 °C and is reactive toward oxygen-atom-transfer and hydrogen-atom-transfer (HAT) reactions. Compared to the parent complex [FeIV(O)(N4Py)]2+, 2is more reactive in oxidizing thioanisole and oxygenates the C–H bonds of aliphatic substrates including that of cyclohexane. The enhanced reactivity of 2toward cyclohexane results from the involvement of the S= 2 transition state in the HAT pathway and a lower triplet-quintet splitting compared to [FeIV(O)(N4Py)]2+, as supported by DFT calculations. The second-order rate constants for HAT by 2is well correlated with the C–H bond dissociation energies of aliphatic substrates. Surprisingly, the slope of this correlation is different from that of [FeIV(O)(N4Py)]2+, and 2is more reactive only in the case of strong C–H bonds (>86 kcal/mol), but less reactive in the case of weaker C–H bonds. Using oxone as the oxidant, the iron(II) complex displays catalytic oxidations of substrates with low activity but with good selectivity.

Spirulina platensiswas cultivated in a vertically aligned photobioreactor for biodiesel synthesis. The algal culture was harvested by centrifugation, and the biomass was dried in an oven. The oil was extracted by solvothermal techniques in a microwave at 60 °C for 30 min and 750 W. The mixed metal oxide (barium–calcium–zinc) heterogeneous catalyst was synthesized and used in biodiesel synthesis from Spirulinaoil. The synthesized catalyst was characterized by using sophisticated techniques, viz thermogravimetric analysis–differential scanning calorimetry, powder X-ray diffraction, attenuated total reflectance–Fourier infrared spectra, scanning electron microscopy–energy-dispersive X-ray spectroscopy, and surface area analyzer. The optimization study was performed on several reaction parameters, such as temperature, time, molar ratio, catalyst weight, and stirring speed. The maximum fatty acid methyl esters conversion was found to be 98.94% at optimized parameters of 2.5 wt % catalyst, 1:18 molar ratio (methanol/oil), 600 rpm stirring speed, and 65 °C temperature for 120 min. Reusability of the catalyst was monitored, and it was found to be reusable for six cycles with 69.56%. The basic site of the catalyst was a function of catalyst activity, which relies on the barium content. Kinetic parameters have been evaluated by applying pseudo-first-order kinetic equation for transesterification of Spirulinaoil. The activation energy (Ea) for the catalyzed transesterification reaction was found to be 48.02 kJ mol–1.

A series of iron(II) benzilate complexes (1–7) with general formula [(L)FeII(benzilate)]+have been isolated and characterized to study the effect of supporting ligand (L) on the reactivity of metal-based oxidant generated in the reaction with dioxygen. Five tripodal N4ligands (tris(2-pyridylmethyl)amine (TPA in 1), tris(6-methyl-2-pyridylmethyl)amine (6-Me3-TPA in 2), N1,N1-dimethyl-N2,N2-bis(2-pyridylmethyl)ethane-1,2-diamine (iso-BPMEN in 3), N1,N1-dimethyl-N2,N2-bis(6-methyl-2-pyridylmethyl)ethane-1,2-diamine (6-Me2-iso-BPMEN in 4), and tris(2-benzimidazolylmethyl)amine (TBimA in 7)) along with two linear tetradentate amine ligands (N1,N2-dimethyl-N1,N2-bis(2-pyridylmethyl)ethane-1,2-diamine (BPMEN in 5) and N1,N2-dimethyl-N1,N2-bis(6-methyl-2-pyridylmethyl)ethane-1,2-diamine (6-Me2-BPMEN in 6)) were employed in the study. Single-crystal X-ray structural studies reveal that each of the complex cations of 1–3and 5contains a mononuclear six-coordinate iron(II) center coordinated by a monoanionic benzilate, whereas complex 7contains a mononuclear five-coordinate iron(II) center. Benzilate binds to the iron center in a monodentate fashion via one of the carboxylate oxygens in 1and 7, but it coordinates in a bidentate chelating mode through carboxylate oxygen and neutral hydroxy oxygen in 2, 3, and 5. All of the iron(II) complexes react with dioxygen to exhibit quantitative decarboxylation of benzilic acid to benzophenone. In the decarboxylation pathway, dioxygen becomes reduced on the iron center and the resulting iron–oxygen oxidant shows versatile reactivity. The oxidants are nucleophilic in nature and oxidize sulfide to sulfoxide and sulfone. Furthermore, complexes 2and 4–6react with alkenes to produce cis-diols in moderate yields with the incorporation of both the oxygen atoms of dioxygen. The oxygen atoms of the nucleophilic oxidants do not exchange with water. On the basis of interception studies, nucleophilic iron(II) hydroperoxides are proposed to generate in situ in the reaction pathways. The difference in reactivity of the complexes toward external substrates could be attributed to the geometry of the O2-derived iron–oxygen oxidant. DFT calculations suggest that, among all possible geometries and spin states, high-spin side-on iron(II) hydroperoxides are energetically favorable for the complexes of 6-Me3-TPA, 6-Me2-iso-BPMEN, BPMEN, and 6-Me2-BPMEN ligands, while high spin end-on iron(II) hydroperoxides are favorable for the complexes of TPA, iso-BPMEN, and TBimA ligands.

Highly effective direct-acting antiviral (DAA) agents have changed the landscape of hepatitis C virus infection (HCV) treatment and have become more available to people who inject drugs (PWID) over the past several years. Although many achieve a sustained virologic response (SVR), a small proportion will become re-infected. This study examined experiences of re-infection among participants in Project HERO, a large multi-site treatment trial designed to test alternative treatment delivery models for DAAs.

Nkx2-5is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5conditional knockout mouse in which flox sites flank the entire Nkx2-5locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2channel and others,shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies.

In spite of being highly preventable through screening strategies and early vaccination, cervical cancer has become the utmost common type of gynaecological malignancy globally and emerged as major cause of death from cancer in women. Estimation have been made that cancer associated with Human papillomavirus (HPV) accounts for 5% of all the cancers. Presently, HPV vaccines are effective in preventing neoplastic disease as well as infection, but they are prophylactic and ineffective in clearing established infection. Owing to which, there is a need for the exploration of therapeutic vaccines that can trigger the immune response for established infection. Moreover, E6 and E7 early genes are stated to be suitable target for the vaccine therapy because of their imperative role in cell cycle disruption and detectable expression in both malignant and pre-malignant tissues. Thus, various therapeutic vaccines like cell-based, nucleic acid-based, protein-based, peptide-based and live-vector vaccines have been developed and few candidate vaccines are now under clinical trials. Furthermore, ineffectiveness of conventional therapies to yield effective result for cervical cancer treatment has shifted the focus of researchers towards nanotechnology for target delivery of therapeutic agent. Hence, this review aims to comprehends the current known knowledge about cervical cancer and conventional approaches for its treatment. It also highlights the recent progressive development in vaccine strategies and nanotechnological approaches for effective management and prevention of cervical cancer.

The isolation, characterization, and dioxygen reactivity of monomeric [(TPA)MII(mandelate)]+(M = Fe, 1; Co, 3) and dimeric [(BPMEN)2MII2(μ-mandelate)2]2+(M = Fe, 2; Co, 4) (TPA = tris(2-pyridylmethyl)amine and BPMEN = N1,N2-dimethyl-N1,N2-bis(pyridin-2-yl-methyl)ethane-1,2-diamine) complexes are reported. The iron(II)- and cobalt(II)-mandelate complexes react with dioxygen to afford benzaldehyde and benzoic acid in a 1:1 ratio. In the reactions, one oxygen atom from dioxygen is incorporated into benzoic acid, but benzaldehyde does not derive any oxygen atom from dioxygen. While no O2-derived intermediate is observed with the iron(II)-mandelate complexes, the analogous cobalt(II) complexes react with dioxygen at a low temperature (−80 °C) to generate the corresponding cobalt(III)-superoxo species (S), a key intermediate implicated in the initiation of mandelate decarboxylation. At −20 °C, the cobalt(II)-mandelate complexes bind dioxygen reversibly leading to the formation of μ-1,2-peroxo-dicobalt(III)-mandelate species (P). The geometric and electronic structures of the O2-derived intermediates (Sand P) have been established by computational studies. The intermediates Sand Pupon treatment with a protic acid undergo decarboxylation to afford benzaldehyde (50%) with a concomitant formation of the corresponding μ-1,2-peroxo-μ-mandelate-dicobalt(III) (P1) species. The crystal structure of a peroxide species isolated from the cobalt(II)-carboxylate complex [(TPA)CoII(MPA)]+(5) (MPA = 2-methoxyphenylacetate) supports the composition of P1. The observations of the dioxygen-derived intermediates from cobalt complexes and their electronic structure analyses not only provide information about the nature of active species involved in the decarboxylation of mandelate but also shed light on the mechanistic pathway of two-electron versus four-electron reduction of dioxygen.

Introduction:The nasal route is an attractive target for administration of the drug of choice, particularly in overcoming disadvantages such as high first-pass metabolism and drug degradation in the gastrointestinal environment that are associated with the oral and other modes of administration. The major limitation associated is of rapid mucociliary clearance in the nasal delivery that results in low absorption and hence poor bioavailability. In order to overcome this, mucoadhesive in situnasal gelling drug delivery systems have been explored to develop sustained/controlled delivery via nasal route.Areas covered:The present review critically evaluates the importance of in situgel for the nasal delivery of drugs, and the polymers used in the formulation of in situgel along with their mechanism of gelation. It also encompasses the research reports made in this arena of delivery system.Expert opinion:The challenges of drug delivery through nose has led to development of in situnasal gelling systems using a myriad of polymers to deliver the drugs, proteins, amino acids, hormones, vaccines and plasmid DNA for the local, systemic and central nervous system effects. Though a range of preclinical reports are available, clinical intricacies need to be critically worked out.

The reaction of CuClO42·6H2O with N4O3coordinating heptadentate H3L1 and N2O coordinating tridentatereduced Schiff base HL2 ligands yielded copperII tetranuclear complexes [Cu4L12]ClO421 and [Cu4L24]ClO442, respectively. Complex 1crystallizes in the cubic system, space group Fd$\bar {3}$c, with unitcell parameters a= b= c= 43.1245 Å, Z= 48, whereas complex 2crystallizes in the space group P41212 in the tetragonal crystal system with Z= 8 and unitcell parameters a= b= 17.1134 Å, c= 44.1504 Å. The Xray structures of 1and 2have revealed a Cu4O6core in 1and a Cu4O4core in 2. Complexes 1and 2show intramolecular antiferromagnetic interaction with moderate |J| values 104.2 cm–1for 1and 155.1 cm–1for 2. The moderate |J| value can be explained by the existence of only one bridging alkoxido group between each pair of copperII atoms and the outofplane displacement of the alkoxido carbon atom from the Cu–O–Cu plane. Brokensymmetry density functional theory BSDFT has been used to justify the exchange pathways.

Two binucleating heptadentate ligands 2,6bis[{[2hydroxybenzylN,Ndimethylaminoethyl]amino}methyl]4methylphenol H3L1 and 2,6bis[{2hydroxybenzylN2pyridylmethylamino}methyl]4methylphenol H3L2 were used to synthesize the two new copperII complexes [Cu2L1N3]·2H2O 1·2H2O and [Cu2HL2O2CPhH2O]PhCO2·H2O 2·H2O. Xray diffraction studies disclose that 1is made up from bridging phenoxido and azido group in an equatorial fashion, whereas 2is bridged axially–equatorially through a central cresolato and syn–synbenzoate moiety. The geometry around the copperII centers is distorted square pyramid in both cases. Variabletemperature magnetic susceptibility data reveals that 1is moderately antiferromagnetically coupled J= –119 cm–1 and 2is very weakly antiferromagnetic J= –1.0 cm–1. The structural features, as well as the presence of orbital countercomplementary effects, are associated with the magnetic behavior. Theoretical calculations with the use of broken symmetry density functional theory also establish the experimental values of the exchange coupling constants J. In our case, only 2exhibits catalytic activity in the oxidation of 3,5ditertbutylcatechol 3,5DTBC at pH 9.5 and hydrolytic cleavage of plasmid DNA in the absence of any added cofactor, whereas complex 1cannot display catecholase activity or DNA interaction as a result of strong CuII–azido binding.© WileyVCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009

Polymeric micelle-based drug delivery systems have been extensively studied by researchers due to their nanoscopic size and low toxicity. In this study, we have designed and synthesized an amphiphilic ursolic acid-polyethylene glycol conjugate, which on self-assembly results in micellar nanostructures. We conjugated ursolic acid (UA) with polyethylene glycol monomethyl ether in a single step in the presence of a condensing reagent, DCC/DMAP, and their self-assembly was monitored by DLS and TEM. Further an anticancer drug, doxorubicin (DOX), was encapsulated into the hydrophobic core of the self-assembled nanostructures. Due to strong interactions between DOX and UA, high encapsulation efficiency (85.3%) was obtained. The release pattern of DOX from the loaded nanostructures showed a sustained release of drug over a period of time. The projected system showed responsiveness towards lipase and hence, biodegradability aspect of the nanostructure (UA-PEG) was also investigated by lipase-mediated degradation studies. MTT experiments were also carried out on both normal HEK293 cells and MG-63 cancer cells and showed the non-toxic nature of the projected conjugate. These results ensure the promising potential of the projected system as an efficient drug delivery vehicle specifically to cancers cells in vivoand in vitro.