Identification of a 10-mer peptide from the death domain of MyD88 which attenuates inflammation and insulin resistance and improves glucose metabolism.

Insulin resistance (IR) is the key pathophysiological cause of type 2 diabetes, and inflammation has been implicated in it. The death domain (DD) of the adaptor protein, MyD88 plays a crucial role in the transduction of TLR4-associated inflammatory signal. Herein, we have identified a 10-residue peptide (M10), from the DD of MyD88 which seems to be involved in Myddosome formation. We hypothesized that M10 could inhibit MyD88-dependent TLR4-signaling and might have effects on inflammation-associated IR. Intriguingly, 10-mer M10 showed oligomeric nature and reversible self-assembly property indicating the peptide's ability to recognize its own amino acid sequence. M10 inhibited LPS-induced nuclear translocation of NF-κB in L6 myotubes and also reduced LPS-induced IL-6 and TNF-α production in peritoneal macrophages of BALB/c mice. Remarkably, M10 inhibited IL-6 and TNF-α secretion in diabetic, db/db mice. Notably, M10 abrogated IR in insulin-resistant L6 myotubes, which was associated with an increase in glucose uptake and a decrease in Ser307-phosphorylation of IRS1, TNF-α-induced JNK activation and nuclear translocation of NF-κB in these cells. Alternate day dosing with M10 (10 and 20 mg/kg) for 30 days in db/db mice significantly lowered blood glucose and improved glucose intolerance after loading, 3.0 g/kg glucose orally. Furthermore, M10 increased insulin and adiponectin secretion in db/db mice. M10-induced glucose uptake in L6 myotubes involved the activation of PI3K/AKT/GLUT4 pathways. A scrambled M10-analog was mostly inactive. Overall, the results show the identification of a 10-mer peptide from the DD of MyD88 with anti-inflammatory and anti-diabetic properties, suggesting that targeting of TLR4-inflammatory pathway, could lead to the discovery of molecules against IR and diabetes.

Tailoring the Photophysical Properties of a Homoleptic Iron(II) Tetra N-Heterocyclic Carbene Complex by Attaching an Imidazolium Group to the (C∧N∧C) Pincer Ligand─A Comparative Study.

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

How Rigidity and Conjugation of Bidentate Ligands Affect the Geometry and Photophysics of Iron N-Heterocyclic Complexes: A Comparative Study.

Two iron complexes featuring the bidentate, nonconjugated N-heterocyclic carbene (NHC) 1,1'-methylenebis(3-methylimidazol-2-ylidene) (mbmi) ligand, where the two NHC moieties are separated by a methylene bridge, have been synthesized to exploit the combined influence of geometric and electronic effects on the ground- and excited-state properties of homoleptic FeIII-hexa-NHC [Fe(mbmi)3](PF6)3 and heteroleptic FeII-tetra-NHC [Fe(mbmi)2(bpy)](PF6)2 (bpy = 2,2'-bipyridine) complexes. They are compared to the reported FeIII-hexa-NHC [Fe(btz)3](PF6)3 and FeII-tetra-NHC [Fe(btz)2(bpy)](PF6)2 complexes containing the conjugated, bidentate mesoionic NHC ligand 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) (btz). The observed geometries of [Fe(mbmi)3](PF6)3 and [Fe(mbmi)2(bpy)](PF6)2 are evaluated through L-Fe-L bond angles and ligand planarity and compared to those of [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The FeII/FeIII redox couples of [Fe(mbmi)3](PF6)3 (-0.38 V) and [Fe(mbmi)2(bpy)](PF6)2 (-0.057 V, both vs Fc+/0) are less reducing than [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The two complexes show intense absorption bands in the visible region: [Fe(mbmi)3](PF6)3 at 502 nm (ligand-to-metal charge transfer, 2LMCT) and [Fe(mbmi)2(bpy)](PF6)2 at 410 and 616 nm (metal-to-ligand charge transfer, 3MLCT). Lifetimes of 57.3 ps (2LMCT) for [Fe(mbmi)3](PF6)3 and 7.6 ps (3MLCT) for [Fe(mbmi)2(bpy)](PF6)2 were probed and are somewhat shorter than those for [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. [Fe(mbmi)3](PF6)3 exhibits photoluminescence at 686 nm (2LMCT) in acetonitrile at room temperature with a quantum yield of (1.2 ± 0.1) × 10-4, compared to (3 ± 0.5) × 10-4 for [Fe(btz)3](PF6)3.

Characterization of Alternaria blotch disease of apple in Himachal Pradesh, India: insights on morphology, pathogenicity, and molecular features.

BACKGROUND: Alternaria blotch disease in Himachal Pradesh, India, caused by Alternaria spp., adversely affects apple cultivars, resulting in reduced fruit size and quality accompanied by premature leaf fall. METHODS AND RESULTS: Sixteen Alternaria isolates from apple growing regions underwent comprehensive analysis including morphology, pathogenicity, and molecular characterization. Variations in conidiophore and conidia dimensions, shapes, and divisions were observed among isolates. Pathogenicity assays revealed differences in incubation periods, latent phases, and disease responses. Molecular characterization via nuclear ITS rDNA and RAPD analysis indicated 99-100% homology with Alternaria alternata, Alternaria mali, and other Alternaria spp., with a close phylogenetic relationship to Chinese isolates. Differentiation of isolates based on origin, cultural characteristics, and morphology was achieved using RAPD markers. CONCLUSIONS: The study identifies diverse genotypes and morphotypes of Alternaria contributing to apple blotch disease in Himachal Pradesh. These findings highlight the complexity of the pathogenic environment and hold significant implications for disease management in apple orchards.

One, Two Three - Phosphaalkene Decoration Tailoring Solubility and Electronic Properties of Truxene-Based Electron Acceptors.

We report the functionalization and deplanarization of truxenes using pnictaalkene fragments. Selective introduction of one, two, or three Mes*-Pn fragments provides up to three fully reversible reductions based on the Pn=C fragments. The incorporation of the unsaturated heteroelement fragment as well as the contortion of the truxene core result in significantly red-shifted absorption spectra and interesting opto-electronic properties which are studied by electrochemistry and spectro-electrochemistry. Incorporation of arsaalkene (As=C) motifs gives significantly milder reduction potentials and red-shifted absorption, while phosphaalkene decorated truxene P3 can be functionalized using Au(I)Cl coordination. Furthermore, solubility is markedly increased upon incorporation of the Pn-Mes* fragments which renders these materials suitable for solution processing.

Photophysical Integrity of the Iron(III) Scorpionate Framework in Iron(III)-NHC Complexes with Long-Lived 2LMCT Excited States.

Fe(III) complexes with N-heterocyclic carbene (NHC) ligands belong to the rare examples of Earth-abundant transition metal complexes with long-lived luminescent charge-transfer excited states that enable applications as photosensitizers for charge separation reactions. We report three new hexa-NHC complexes of this class: [Fe(brphtmeimb)2]PF6 (brphtmeimb = [(4-bromophenyl)tris(3-methylimidazol-2-ylidene)borate]-, [Fe(meophtmeimb)2]PF6 (meophtmeimb = [(4-methoxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-, and [Fe(coohphtmeimb)2]PF6 (coohphtmeimb = [(4-carboxyphenyl)tris(3-methylimidazol-2-ylidene)borate]-. These were derived from the parent complex [Fe(phtmeimb)2]PF6 (phtmeimb = [phenyltris(3-methylimidazol-2-ylidene)borate]- by modification with electron-withdrawing and electron-donating substituents, respectively, at the 4-phenyl position of the ligand framework. All three Fe(III) hexa-NHC complexes were characterized by NMR spectroscopy, high-resolution mass spectroscopy, elemental analysis, single crystal X-ray diffraction analysis, electrochemistry, Mößbauer spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and quantum chemical calculations. Their ligand-to-metal charge-transfer (2LMCT) excited states feature nanosecond lifetimes (1.6-1.7 ns) and sizable emission quantum yields (1.7-1.9%) through spin-allowed transition to the doublet ground state (2GS), completely in line with the parent complex [Fe(phtmeimb)2]PF6 (2.0 ns and 2.1%). The integrity of the favorable excited state characteristics upon substitution of the ligand framework demonstrates the robustness of the scorpionate motif that tolerates modifications in the 4-phenyl position for applications such as the attachment in molecular or hybrid assemblies.

MERCI: a machine learning approach to identifying hydroxychloroquine retinopathy using mfERG.

PURPOSE: Hydroxychloroquine (HCQ) is an anti-inflammatory drug in widespread use for the treatment of systemic auto-immune diseases. Vision loss caused by retinal toxicity is a significant risk associated with long term HCQ therapy. Identifying patients at risk of developing retinal toxicity can help prevent vision loss and improve the quality of life for patients. This paper presents updated reference thresholds and examines the diagnostic accuracy of a machine learning approach for identifying retinal toxicity using the multifocal Electroretinogram (mfERG). METHODS: A retrospective study of patients referred for mfERG testing to detect HCQ retinopathy. A consecutive series of all patients referred to Kensington Vision and Research Centre between August 2017 and July 2020 were considered eligible. Eyes suspect for other ocular pathology including widespread retinal disease and advanced macular pathology unrelated to HCQ or with poor quality mfERG recordings were excluded. All patients received mfERG testing and Ocular Coherence Tomography (OCT) imaging. Presence of HCQ retinopathy was based on ring ratio analysis using clinical reference thresholds established at KVRC coupled with structural features observed on OCT, the clinical reference standard. A Support Vector Machine (SVM) using selected features of the mfERG was trained. Accuracy, sensitivity and specificity are reported. RESULTS: 1463 eyes of 748 patients were included in the study. SVM model performance was assessed on 293 eyes from 265 patients. 55 eyes from 54 patients were identified as demonstrating HCQ retinopathy based on the clinical reference standard, 50 eyes from 49 patients were identified by the SVM. Our SVM achieves an accuracy of 85.3% with a sensitivity of 90.9% and specificity of 84.0%. CONCLUSIONS: Machine learning approaches can be applied to mfERG analysis to identify patients at risk of retinopathy caused by HCQ therapy.

Reference intervals for reticulocyte parameters (reticulocyte haemoglobin equivalent and immature reticulocyte fraction) in first-trimester pregnancy.

Reticulocyte parameters including reticulocyte haemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are newly recognised hematological parameters that are being used for diagnosis and follow-up of anaemic patients. Reference intervals of these parameters have been established in different populations, however, the data relating to pregnancy are still lacking. One hundred and fifty-five first-trimester pregnant females were screened and the reference interval was calculated after selecting the patient with fixed criteria. R statistical software was used for statistical calculations. We tried to establish a reference interval of Ret-He content and IRF in first-trimester pregnancy in our study.IMPACT STATEMENTWhat is already known on this subject? Ret-He and IRF have been established as the marker of iron deficiency and iron-deficiency anaemia in different age groups and as a marker of response to iron therapy. However, literature is scarce regarding the reference intervals of these parameters, especially in pregnancy.What do the results of this study add? This study establishes the reference interval of newer reticulocyte parameters in first-trimester pregnancy which is not yet established in the literature. Establishing a reference interval is required for any laboratory parameters to be used in the clinical context.What are the implications of these findings for clinical practice and further research? The results of this study may help in making a clinical decision regarding iron deficiency in early pregnancy which is one of the common clinical problems in pregnancy. This study also serves as a baseline study for further studies of reference intervals for newer reticulocyte parameters in pregnancy. A similar study with a larger study population and follow-up with iron therapy may establish these parameters as one of the important markers of iron deficiency in pregnancy and help institute iron therapy on case-to-case basis.

Prognostic Role of Ngal in Critically Ill Patients.

Acute kidney injury (AKI) is a frequently encountered outcome in critically ill patients, accounting for increased mortality. Neutrophil gelatinase associated lipocalin (NGAL) has been of paramount importance as a novel biomarker of AKI. This study is an attempt to assess the use of NGAL in critically ill patients so that timely interventions can be done to reduce morbidity and mortality in such patients. MATERIAL: A prospective observational study was conducted at SRN Hospital, Prayagraj from August 1st 2020 to March 15th 2021, which included only critically ill patients with SOFA score>1 and requiring ICU admission. Patients of known renal diseases were excluded from the study. Blood as well as urinary samples for NGAL and other laboratory parameters were collected within 8 hours of admission. Patients who developed renal dysfunction were noted as our cases and the others were noted as controls. OBSERVATION: The study was done on 125 patients, out of which 67 developed AKI while 58 did not develop AKI. Higher mortality was seen in patients with higher stage of AKI (P- 0.011). The cutoff of serum and urinary NGAL for predicting AKI were >42.3 ng/mL, >40.5 ng/mL respectively (P value <0.001). Hazard Ratio for all cause mortality of raised serum and urinary NGAL was 2.0062 (p value- 0.0001, 95% CI-1.0031 to 1.0092) and 2.0046 (p value-0.0035, 95% CI-1.0015 to 1.0078) respectively. Serum and urinary neutrophil gelatinase associated lipocalin at values >91 and >131 respectively were found to predict requirement of hemodialysis (p value<0.001). CONCLUSION: A single measurement of NGAL at the time of admission had good predictive ability for AKI. Higher values of NGAL were associated with staging of AKI and thus, correlated with need of hemodialysis. Furthermore, mortality was found to be associated with development of AKI and raised NGAL. Thus, NGAL maybe used to assess the prognosis of ICU patients so that patients at high risk may be managed aggressively, thus reducing mortality.

Three-in-One C2 H2 -Selectivity-Guided Adsorptive Separation across an Isoreticular Family of Cationic Square-Lattice MOFs.

Energy-efficient selective physisorption driven C2 H2 separation from industrial C2-C1 impurities such as C2 H4 , CO2 and CH4 is of great importance in the purification of downstream commodity chemicals. We address this challenge employing a series of isoreticular cationic metal-organic frameworks, namely iMOF-nC (n=5, 6, 7). All three square lattice topology MOFs registered higher C2 H2 uptakes versus the competing C2-C1 gases (C2 H4 , CO2 and CH4 ). Dynamic column breakthrough experiments on the best-performing iMOF-6C revealed the first three-in-one C2 H2 adsorption selectivity guided separation of C2 H2 from 1:1 C2 H2 /CO2 , C2 H2 /C2 H4 and C2 H2 /CH4 mixtures. Density functional theory calculations critically examined the C2 H2 selective interactions in iMOF-6C. Thanks to the abundance of square lattice topology MOFs, this study introduces a crystal engineering blueprint for designing C2 H2 -selective layered metal-organic physisorbents, previously unreported in cationic frameworks.

Luminol-Based Turn-On Fluorescent Sensor for Selective and Sensitive Detection of Sulfur Mustard at Ambient Temperature.

We have explored a novel turn-on fluorescence detection of sulfur mustard (SM) at "room temperature". The innovative protocol that uses the combination of luminol and an ionic liquid in water exhibits fluorescence detection of SM within seconds. In this simple, fast, and low-cost chemosensing method, luminol acts as the receptor as well as a signaling element, and the ionic liquid (1-ethyl-3-methylimidazolium dicyanamide) provides the requisite and polarizing medium to realize the detection at "room temperature". Interestingly, with a higher concentration of a probe (0.56 mM), SM sensing can be visualized with the naked eye, leading to the formation of a fluorescent green color within a minute, thus expanding the application of the developed sensing technique for chromo-fluorogenic detection of SM. Excellent selectivity, sensitivity (LOD: 6 ppm), and chemosensing at ambient temperature make this methodology completely field-deployable.

[Cu{SC(O)OiPr}]96: A Giant Self-Assembled Copper(I) Supramolecular Wheel Exhibiting Photoluminescence Tuning and Correlations with Dynamic Solvation and Solventless Synthesis.

The hierarchical self-organization of structurally complex high-nuclearity metal clusters with metallosupramolecular wheel architectures that are obtained from the self-assembly of smaller solvated cluster units is rare and unique. Here, we use the potentially heteroditopic monothiocarbonate ligand and demonstrate for the first time the synthesis and structure of a solvated non-cyclic hexadecanuclear cluster [Cu{SC(O)OiPr}]16·2THF (1) that can simultaneously desolvate and self-assemble in solution and subsequently form a giant metallaring, [Cu{SC(O)OiPr}]96 (2). We also demonstrate a luminescent precursor to cluster (2) can be achieved through a solventless and rapid mechanochemical synthesis. Cluster (2) is the highest nuclearity copper(I) wheel and the largest metal cluster containing a heterodichalcogen (O, S) ligand reported to date. Cluster (2) also exhibits solid-state luminescence with relatively long emission lifetimes at 4.1, 13.9 (µs). The synthetic strategy described here opens new research avenues by replacing solvent molecules in stable {Cu16} clusters with designed building units that can form new hybrid and multifunctional finite supramolecular materials. This finding may lead to the development of novel high-nuclearity materials self-assembled in a facile manner with tunable optical properties.

Biological Synthesis of PbS, As3S4, HgS, CdS Nanoparticles using Pseudomonas aeruginosa and their Structural, Morphological, Photoluminescence as well as Whole Cell Protein Profiling Studies.

Metal sulfide nanoparticles are semi-conductors that possess many applications in optics, optoelectronics and magnetic devices. There are physical and chemical methods for their synthesis but such methods involve toxic precursors as well as many obnoxious by-products. Hence, biological synthesis of metal sulfide nanoparticles are efficient enough to transform toxic metals to non-toxic ones. Pseudomonas aeruginosa, isolated from textile effluent and tolerant of high levels of heavy metals, was used for the green synthesis of metal sulfide (HgS, As3S4, CdS and PbS) nanoparticles. The optical, structural and morphological nature of metal sulfide nanoparticles was also determined. FTIR (Fourier Transform Infra-red) analysis showed spectral changes when P. aeruginosa was grown in medium containing heavy metals viz. Hg, As, Pb and Cd indicating that there are functional groups viz. carboxyl, hydroxyl, phosphate, amino and amide, that exists on the surface of the bacteria, thus facilitating binding of metals on its surface. The bacterial samples which were treated with different metals at different concentrations, were subjected to whole cell protein analysis using SDS-PAGE (Sodium dodecyl Sulphate- Polyacrylamide gel electrophoresis) and protein profiling. The total protein estimation revealed that there was an increase in the protein concentration in the presence of heavy metals and a significant change in the banding pattern was observed which showed induction of a set of proteins under heavy metal stress especially mercury.

Oxygenated Cyclohexene Derivatives from the Stem and Root Barks of Uvaria pandensis.

Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A-C (3-5), and 16 known secondary metabolites (6-21) were isolated from the methanol-soluble extracts of the stem and root barks of Uvaria pandensis. The structures were characterized by NMR spectroscopic and mass spectrometric analyses, and that of 6-methoxyzeylenol (6) was further confirmed by single-crystal X-ray crystallography, which also established its absolute configuration. The isolated metabolites were evaluated for antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis and the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum, and Pseudomonas putida, as well as for cytotoxicity against the MCF-7 human breast cancer cell line. A mixture of uvaretin (20) and isouvaretin (21) exhibited significant antibacterial activity against B. subtilis (EC50 8.7 µM) and S. epidermidis (IC50 7.9 µM). (8'α,9'ß-Dihydroxy)-3-farnesylindole (12) showed strong inhibitory activity (EC50 9.8 µM) against B. subtilis, comparable to the clinical reference ampicillin (EC50 17.9 µM). None of the compounds showed relevant cytotoxicity against the MCF-7 human breast cancer cell line.

Spatial network based model forecasting transmission and control of COVID-19.

The SARS-CoV-2 driven infectious novel coronavirus disease (COVID-19) has been declared a pandemic by its brutal impact on the world in terms of loss on human life, health, economy, and other crucial resources. To explore more about its aspects, we adopted the S E I R D (Susceptible-Exposed-Infected-Recovered-Death) pandemic spread with a time delay on the heterogeneous population and geography in this work. Focusing on the spatial heterogeneity, epidemic spread on the framework of modeling that incorporates population movement within and across the boundaries is studied. The entire population of interest in a region is divided into small distinct geographical sub regions, which interact using migration networks across boundaries. Utilizing the time delay differential equations based model estimations, we analyzed the spread dynamics of disease in India. The numerical outcomes from the model are validated using real time available data for COVID-19 cases. Based on the developed model in the framework of the recent data, we verified total infection cases in India considering the effect of nationwide lockdown at the onset of the pandemic and its unlocking by what seemed to be the end of the first wave. We have forecasted the total number of infection cases in two extreme situations of nationwide no lockdown and strict lockdown scenario. We expect that in future for any change in the key parameters, due to the regional differences, predictions will lie within the bounds of the above mentioned extreme plots. We computed the approximate peak infection in forwarding time and relative timespan when disease outspread halts. The most crucial parameter, the time-dependent generalization of the basic reproduction number, has been estimated. The impact of the social distancing and restricted movement measures that are crucial to contain the pandemic spread has been extensively studied by considering no lockdown scenario. Our model suggests that attaining a reduction in the contact rate between susceptible and infected individuals by practicing strict social distancing is one of the most effective control measures to manage COVID-19 spread in India. The cases can further decrease if social distancing is followed in conjunction with restricted movement.

Network synchronization, stability and rhythmic processes in a diffusive mean-field coupled SEIR model.

Connectivity and rates of movement have profound effect on the persistence and extinction of infectious diseases. The emerging disease spread rapidly, due to the movement of infectious persons to some other regions, which has been witnessed in case of novel coronavirus disease 2019 (COVID-19). So, the networks and the epidemiology of directly transmitted infectious diseases are fundamentally linked. Motivated by the recent empirical evidence on the dispersal of infected individuals among the patches, we present the epidemic model SEIR (Susceptible-Exposed-Infected-Recovered) in which the population is divided into patches which form a network and the patches are connected through mean-field diffusive coupling. The corresponding unstable epidemiology classes will be synchronized and achieve stable state when the patches are coupled. Apart from synchronization and stability, the coupled model enables a range of rhythmic processes such as birhythmicity and rhythmogenesis which have not been investigated in epidemiology. The stability of Disease Free Equilibrium (or Endemic Equilibrium) is attained through cessation of oscillation mechanism namely Oscillation Death (OD) and Amplitude Death (AD). Corresponding to identical and non-identical epidemiology classes of patches, the different steady states are obtained and its transition is taking place through Hopf and transcritical bifurcation.

Catalytic Activity of trans-Bis(pyridine)gold Complexes.

Gold catalysis has become one of the fastest growing fields in chemistry, providing new organic transformations and offering excellent chemoselectivities under mild reaction conditions. Methodological developments have been driven by wide applicability in the synthesis of complex structures, whereas the mechanistic understanding of Au(III)-mediated processes remains scanty and have become the Achilles' heel of methodology development. Herein, the systematic investigation of the reactivity of bis(pyridine)-ligated Au(III) complexes is presented, based on NMR spectroscopic, X-ray crystallographic, and DFT data. The electron density of pyridines modulates the catalytic activity of Au(III) complexes in propargyl ester cyclopropanation of styrene. To avoid strain induced by a ligand with a nonoptimal nitrogen-nitrogen distance, bidentate bis(pyridine)-Au(III) complexes convert into dimers. For the first time, bis(pyridine)Au(I) complexes are shown to be catalytically active, with their reactivity being modulated by strain.

Impact of Excited-State Antiaromaticity Relief in a Fundamental Benzene Photoreaction Leading to Substituted Bicyclo[3.1.0]hexenes.

Benzene exhibits a rich photochemistry which can provide access to complex molecular scaffolds that are difficult to access with reactions in the electronic ground state. While benzene is aromatic in its ground state, it is antiaromatic in its lowest ππ* excited states. Herein, we clarify to what extent relief of excited-state antiaromaticity (ESAA) triggers a fundamental benzene photoreaction: the photoinitiated nucleophilic addition of solvent to benzene in acidic media leading to substituted bicyclo[3.1.0]hex-2-enes. The reaction scope was probed experimentally, and it was found that silyl-substituted benzenes provide the most rapid access to bicyclo[3.1.0]hexene derivatives, formed as single isomers with three stereogenic centers in yields up to 75% in one step. Two major mechanism hypotheses, both involving ESAA relief, were explored through quantum chemical calculations and experiments. The first mechanism involves protonation of excited-state benzene and subsequent rearrangement to bicyclo[3.1.0]hexenium cation, trapped by a nucleophile, while the second involves photorearrangement of benzene to benzvalene followed by protonation and nucleophilic addition. Our studies reveal that the second mechanism is operative. We also clarify that similar ESAA relief leads to puckering of S1-state silabenzene and pyridinium ion, where the photorearrangement of the latter is of established synthetic utility. Finally, we identified causes for the limitations of the reaction, information that should be valuable in explorations of similar photoreactions. Taken together, we reveal how the ESAA in benzene and 6π-electron heterocycles trigger photochemical distortions that provide access to complex three-dimensional molecular scaffolds from simple reactants.

Evaluation of platelet distribution width as novel biomarker in gall bladder cancer.

INTRODUCTION: Gall bladder cancer (GBC) tends to present in advanced stages, therefore, early diagnosis of GBC is necessary. There is no ideal single tumor marker available presently for the diagnosis and prognosis of GBC. Platelet distribution width (PDW) is an early marker for activated platelets and has been used in a variety of tumors to assess prognosis. This study was designed to evaluate the utility of PDW in identifying GBC patients and its association with tumor markers, staging and resectability of GBC. MATERIALS AND METHODS: This cross sectional study was done on 100 patients of GBC and 100 age- and sex- matched healthy controls. PDW was evaluated and compared between GBC and healthy controls. Receiver-operating characteristics was plotted to determine optimal cut-off for identifying GBC patients and to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PDW. Correlation between serum tumor markers (carbohydrate antigen 19-9, carcinoembryonic antigen, and carbohydrate antigen 125) and PDW were evaluated. Association of PDW with hyperbilirubinemia, staging and resectability of GBC was also studied. RESULTS: A significantly higher PDW with a median of 18.1 was observed in GBC as compared to healthy controls with median value of 13. PDW was found to have a very high sensitivity (90%), specificity (95%), PPV (94%) and NPV (90%) in identifying GBC at cut-off of 16 with area under the curve (AUC) of 0.97. An increase of PDW was observed with increasing stage and unresectable GBC. However, it was not statistically significant. Significant positive correlation was observed between PDW and all three serum tumor markers and good positive correlation with r = 0.61 was observed with CA 19-9. CONCLUSION: PDW was associated with GBC and may be considered as a cost- effective marker in adjunct to other investigations for the diagnosis of GBC.

Golden Age of Fluorenylidene Phosphaalkenes-Synthesis, Structures, and Optical Properties of Heteroaromatic Derivatives and Their Gold Complexes.

The substitution of 2,7-dibromo-9-fluorenyl phosphaalkenes with heteroaromatic substituents (bithiophene, benzothiophene, pyridine) offers access to interesting push-pull dye molecules. Steric shielding due to the bulky P-substituent gives marked different reactivities at the 2- and 7-positions, allowing the synthesis of mixed/asymmetric derivatives. Further functionalization via gold(I) coordination was demonstrated and increased the acceptor character, concomitant with a red-shifted absorption.