Electrochemical Oxidative Addition of Nucleophiles on 2-Arylindoles: Synthesis of C2-Heteroquaternary Indolin-3-ones.

An electrochemical method has been developed to synthesize 2,2-disubstituted indolin-3-ones under mild conditions. A series of nucleophiles have been added to the 2-arylindole-3-ones, generated in situ under metal-free electrochemical oxidative dearomatization of 2-arylindoles, to afford 2,2-disubstituted 3-carbonyl indoles with heteroquaternary centers in 57-79% yields.

Catalyst-free direct regiospecific multicomponent synthesis of C3-functionalized pyrroles.

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of ß-(C3)-substituted pyrroles has been developed. The enamine intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal-Knorr reaction in a direct multicomponent "just-mix" fashion to furnish pyrroles with overall good yields. Several C3-substituted N-alkyl/aryl/H pyrroles have been produced under open-flask conditions with high atom economy and avoiding protection-deprotection chemistry.

Electrochemical Oxidative Coupling Between Benzylic C(sp3)-H and N-H of Secondary Amines: Rapid Synthesis of α-Amino α-Aryl Esters.

An intermolecular electrochemical coupling between the benzylic C(sp3)-H bond and various secondary amines is reported. The electronic behavior of two electronically rich units viz the α-position of α-aryl acetates and amines was engineered electrochemically, thus facilitating their reactivity for the direct access of α-amino esters. A series of acyclic/cyclic secondary amines and α-aryl acetates were tested to furnish the corresponding α-amino esters with high yields (up to 92%) under mild conditions.

Two-pot synthesis and photophysical studies of 1,6-disubstituted 5-aza-indoles from succinaldehyde and N-aryl propargylic-imines.

A two-pot synthesis of 5-aza-indoles has been developed from aqueous succinaldehyde and N-aryl propargylic-imines. This overall protocol involves: (i) the metal-free [3 + 2] annulation of aqueous succinaldehyde and N-aryl propargylic-imines to access 2-alkynyl-pyrrole-3-aldehydes and (ii) Ag-catalyzed 6-endo-dig-cyclization to obtain substituted 5-aza-indoles in the second pot. The 5-aza-indoles showed engaging photophysical activities, and the practicality of this pot-economic gram-scale synthesis has been demonstrated.

Direct Amine-Catalyzed Enantioselective Synthesis of Pentacyclic Dibenzo[b,f][1,4]oxazepine/Thiazepine-Fused Isoquinuclidines along with DFT Calculations.

A direct protocol for the asymmetric synthesis of dibenzoxazepine/thiazepine-fused [2.2.2] isoquinuclidines is developed. The reaction proceeds through a proline-catalyzed direct Mannich reaction followed by an intramolecular aza-Michael cascade sequence between 2-cyclohexene-1-one and various tricyclic imines, like dibenzoxazepines/thiazepines, as an overall [4 + 2] aza-Diels-Alder reaction. A series of pentacyclic isoquinuclidines have been prepared, with complete endo-selectivity, in good to high yields and excellent enantioselectivity (>99:1). Density functional theory (DFT) calculations further support the observed high stereochemical outcome of the reaction.

Sequential multicomponent site-selective synthesis of 4-iodo and 5-iodopyrrole-3-carboxaldehydes from a common set of starting materials by tuning the conditions.

A simple and straightforward method for the synthesis of 4-iodo and 5-iodopyrrole-3-carboxaldehydes is developed from a common set of starting materials by tuning the reaction conditions. This sequential multicomponent protocol involves I2-mediated regioselective C4-iodination and aromatization of intermediate dihydropyrrole, generated through proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and imines, to access 4-iodopyrroles. While aerobic oxidative aromatization of dihydropyrrole to pyrrole followed by NIS-mediated regioselective iodination furnished 5-iodopyrroles in a two-pot fashion. A series of site-selective C4/C5-iodopyrroles have been synthesized in good to high yields (up to 78%) and DFT calculations of these compounds were also performed.

Enantio- and Diastereoselective Two-Pot Synthesis of Isoquinuclidines from Glutaraldehyde and N-Aryl Imines with DFT Calculations.

A pot-economic method for the enantio- and diastereoselective synthesis of a [2.2.2] azabicyclic isoquinuclidine system is developed. This protocol involves the proline-catalyzed direct Mannich reaction-cyclization/IBX-mediated site-selective oxidation/NaBH4-reduction sequence between glutaraldehyde and imines to generate in situ chiral 1,2-DHPs, followed by the diastereoselective Diels-Alder reaction with N-aryl maleimides furnishing isoquinuclidines in overall five steps. A variety of isoquinuclidines having five-contiguous chiral centers, including an all-carbon quaternary, were prepared with high yields (up to 78%) and excellent stereoselectivity (>50:1 dr, and up to >99:1 er). DFT calculations support the observed high stereoselective reaction outcome.

One-Pot Synthesis of Chiral Tetracyclic Dibenzo[ b, f][1,4]oxazepine-Fused 1,2-Dihydropyridines (DHPs) under Metal-Free Conditions.

An efficient protocol for the catalytic asymmetric synthesis of new dibenzo[ b, f][1,4]-oxazepine-fused 1,2-dihydropyridines (DHPs) has been described under metal-free conditions. This reaction proceeds through proline-catalyzed direct Mannich/cyclization between seven-membered dibenzo[ b, f][1,4]-oxazepine-imines and aqueous glutaraldehyde, followed by IBX-mediated site-selective dehydrogenative oxidation in one-pot operation with high yields (up to 92%) and excellent enantioselectivity (up to >99:1 er).

Rapid Three-Dimensional Printing in Water Using Semiconductor-Metal Hybrid Nanoparticles as Photoinitiators.

Additive manufacturing processes enable fabrication of complex and functional three-dimensional (3D) objects ranging from engine parts to artificial organs. Photopolymerization, which is the most versatile technology enabling such processes through 3D printing, utilizes photoinitiators that break into radicals upon light absorption. We report on a new family of photoinitiators for 3D printing based on hybrid semiconductor-metal nanoparticles. Unlike conventional photoinitiators that are consumed upon irradiation, these particles form radicals through a photocatalytic process. Light absorption by the semiconductor nanorod is followed by charge separation and electron transfer to the metal tip, enabling redox reactions to form radicals in aerobic conditions. In particular, we demonstrate their use in 3D printing in water, where they simultaneously form hydroxyl radicals for the polymerization and consume dissolved oxygen that is a known inhibitor. We also demonstrate their potential for two-photon polymerization due to their giant two-photon absorption cross section.

Pulmonary Renal Syndrome: Experience from Tertiary Centre in Mumbai.

INTRODUCTION: Pulmonary Renal Syndrome (PRS), is characterized by diffuse alveolar haemorrhage (DAH) and glomerulonephritis (GN), occurring simultaneously. It has high mortality and dialysis dependence at one year, if not timely diagnosed and aggressively treated. OBJECTIVES: To study etiology and short term outcome of PRS in India. MATERIALS AND METHODS: This study included patients of PRS seen in a tertiary care center in Mumbai, by one consultant from 1997- 2013, analyzed retrospectively and from January 2014 to December 2015 collected prospectively from six medical units, intensive care unit, nephrology and respiratory units. Patients with DAH (haemoptysis, breathlessness and x-ray chest with bilateral alveolar shadows with sparing of apices) and glomerulonephritis (Proteinuria, heamaturia, hypertension with or without raised serum Creatinine) were included in the study after carefully excluding other causes of haemoptysis and breathless like tuberculosis, pulmonary oedema, pneumonia, ARDS. During prospective enrollment of patients, in all admitted patients with haemoptysis, urine examination was carried out to specifically look for proteinuria and red blood cells in urine, same was also followed in those admitted for breathlessness with chest x-ray suggestive of alveolar haemorrhage. Patients were extensively investigated for etiology and were treated with steroids and pulse cyclophosphamide (after ruling out infectious etiology). Supportive care with ventilator or dialysis was given as per usual indications. Palsmapheresis was initiated in those with serum Creatinine ≥ 5.7mg/dl. Rituximab was used in refractory cases, as per treating physicians' choice. Final outcome was death or discharge. RESULTS: There were 25 patients of PRS (13 retrospective, 12 prospective), with following etiology : Granulomatosis with polyangiitis (GPA) 7, Microscopic polyangiitis (MPO) 4, Churg Strauss Syndrome (EGPA) 1, Goodpasture's syndrome 1, lupus 5, leptospirosis 5, dengue 2. All were given steroids, 18 (72%) were given pulse Cyclophosphamide (barring those with leptospirosis and dengue), ventilator support in 14 (56%) patients (8 invasive, 6 non-invasive), haemodialysis 3, plasmapheresis 1, Rituximab 2. Seventeen (68%) patients survived, mortality was high in those requiring invasive ventilator. CONCLUSION: Most common etiology of PRS is ANCA positive vasculitis in India. With high degree of suspicion for DAH in patients presenting with haemoptysis, breathlessness and alveolar opacities in chest x-ray and carefully investigating by simple urine examination for evidence of GN, timely diagnosis of PRS can be made. With timely appropriate treatment survival is 68%. Patients with PRS due to leptospirosis or dengue have features suggestive of underlying disease (like icterus with raised bilirubin but < 200U SGOT/SGPT, subconjunctival haemorrhage, typical rash of dengue with thrombocytopenia).

First intrauterine transfusion in Rh isoimmunised triplet pregnancy.

G3P2L1, 28+4 weeks of gestation rhesus (Rh) isoimmunised pregnant women, was referred with trichorionic triamniotic triplet pregnancy with Rh antibody titres of 1:32. Nuchal translucency and anomaly scan were within normal limits with no major malformation for any of the fetuses. Obstetric colour Doppler with middle cerebral artery peak systolic volume revealed foetal anaemia in all three fetuses having velocities corresponding to around 1.5 times the median. Decision of intrauterine transfusion of blood to all three fetuses was taken. Access to fetuses was challenging and expertise in interventional ultrasound was required for transfusion. The patient tolerated the procedure well and eventually went on to deliver uneventfully at 34 weeks of gestation for worsening pre-eclampsia. After birth, all three triplets received triple-surface intensive phototherapy and intravenous immunoglobulin at a dosage of 1 g/kg. Phototherapy was gradually reduced and discontinued within 72 hours, and the infants were discharged from the neonatal intensive care unit at 96 hours of age.

Significance of Ionic Character Induced by Ga-Doped γ-Al2O3 on Polyethylene Degradation to the Precursors of Gasoline and Diesel Oil with a Trace Amount of Wax.

Polyethylene degradation has a significant ecological impact but is also economically beneficial because it generates fuels and useful chemical products. Our study mainly describes the cleavage of C-C and C-H bonds when polyethylene (dispersed in 1-octadecene) was low-temperature heat-treated in two steps, at 180 and 250 °C, for 24 h for each step. Finally, it was converted to a mixture of the precursors of gasoline and diesel oil with a trace amount of wax. A series of reactions resulted in cracking, dehydrogenation and oxidation, hence producing polycarboxylic acids and saturated and unsaturated hydrocarbons. ESI-MS analysis revealed that mixed oil consisted of low carbon number hydrocarbons and their derivatives of carboxylic acids, with the carbon number ranging from C-6 to C-18. In the trace amount of wax, complicated carboxylic acids and hydrocarbons with carbon number C-22 to C-58 were also identified. FT-IR analysis further confirmed the presence of carboxylic acid derivatives and double bonds in the degradation products. γ-Al2O3 nanorods effectively catalyzed the degradation process by enhancing the C-C chain length in the products. Lewis acid (Al) and Lewis base (oxygen) in the γ-Al2O3 induced ionic character of the C-C bond chain, which led to the efficient cracking of the C-C bond. Poor shielding effect, smaller atomic size and greater ionization energy made Ga a stronger Lewis acid compared to Al; hence, Ga-doped γ-Al2O3 catalyzed the degradation process even more effectively.

Enantioselective Direct Synthesis of C3-Hydroxyalkylated Pyrrole via an Amine-Catalyzed Aldol/Paal-Knorr Reaction Sequence.

Creating functionality with chirality at position C3 of pyrrole is challenging. An operationally simple organocatalytic method has been developed to generate functionality with a chiral tertiary/quaternary stereocenter at position C3 of pyrrole. The process proceeds through an amine-catalyzed direct aldol reaction of succinaldehyde with various acceptor carbonyls, followed by a Paal-Knorr reaction with a primary amine in the same pot. A series of chiral C3-hydroxyalkylated N-alkyl/Ar/H-pyrroles have been synthesized for the first time with good to high yields and excellent enantioselectivity.

Synthesis of Uniform Size Rutile TiO2 Microrods by Simple Molten-Salt Method and Its Photoluminescence Activity.

Uniform-size rutile TiO2 microrods were synthesized by simple molten-salt method with sodium chloride as reacting medium and different kinds of sodium phosphate salts as growth control additives to control the one-dimensional (1-D) crystal growth of particles. The effect of rutile and anatase ratios as a precursor was monitored for rod growth formation. Apart from uniform rod growth study, optical properties of rutile microrods were observed by UV-visible and photoluminescence (PL) spectroscopy. TiO2 materials with anatase and rutile phase show PL emission due to self-trapped exciton. It has been observed that synthesized rutile TiO2 rods show various PL emission peaks in the range of 400 to 900 nm for 355 nm excitation wavelengths. All PL emission appeared due to the oxygen vacancy present inside rutile TiO2 rods. The observed PL near the IR range (785 and 825 nm) was due to the formation of a self-trapped hole near to the surface of (110) which is the preferred orientation plane of synthesized rutile TiO2 microrods.

Defectronics based photoelectrochemical properties of Cu2+ ion doped hematite thin film.

The concentration of guest elements (dopants) into host materials play an important role in changing their intrinsic electrical and optical properties. The existence of hetero-element induce defect in crystal structure, affecting conductivity. In the current work, we report Cu2+ ion into hematite in the defectronics point of view and their photoelectrochemical properties. Crystal distortion in the structure of hematite is observed as the amount of dopant increases. Among 1, 3 and 5 mol% of Cu2+ doped hematite, the existence of 1 mol% of Cu2+ ion into hematite crystal structure produce photocurrent value of 0.15 mA/cm2, IPCE value of ~ 4.7% and EIS value of ~ 2000 Ω/cm2 as best performances. However, further increasing dopants increases the number of interstitial defects, which cause the deformation of intrinsic lattice structure.

Novel eco-friendly low cost and energy efficient synthesis of (Nd-Pr-Dy)2Fe14B magnetic powder from monazite concentrate.

Syntheses of Nd2Fe14B magnetic powder by conventional method is a complicated multi-step process, which produces harmful pollutants and consumes a huge amount of energy and resources. Herein we report a simple chemical route for the preparation of (Nd-Pr)2Fe14B magnetic powder using monazite concentrate as a precursor. Th, U, Sm, and La impurities were removed from monazite leachate by roasting, solvent extraction and leaching the concentrate. Purified leachate consisting of Nd and Pr Chlorides was added to the FeCl3 solution, and the solution produced was co-precipitated with NaOH. RE and Fe hydroxide precipitates were converted to the oxides by annealing at 700 °C. Boric acid and CaH2 were added in the RE and Fe oxides produced, and this mixture was reduced and diffused to (Nd-Pr)2Fe14B. Magnetic properties of the (Nd-Pr)2Fe14B produced were enhanced by introducing antiferromagnetic coupling, induced by Dy addition and efficient removal of CaO byproduct through ball milling in ethanol which increased the BHmax from 3.9 to 11.45 MGOe. Process reported is energy efficient, environment-friendly, time saving and low-cost.

Direct catalytic synthesis of ß-(C3)-substituted pyrroles: a complementary addition to the Paal-Knorr reaction.

The synthesis of ß-(C3)-functionalized pyrroles is a challenging task and requires a multistep protocol. An operationally simple direct catalytic synthesis of ß-substituted pyrroles has been developed. This one-pot multicomponent method combined aqueous succinaldehyde as 1,4-dicarbonyl, primary amines, and isatins to access hydroxyl-oxindole ß-tethered pyrroles. Direct synthesis of the ß-substituted free NH-pyrrole is the central intensity of this work. DFT-calculations and preliminary mechanism investigation support the possible reaction pathway.

Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity.

Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Abeta42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Abeta42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Abeta and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism.

Novel Technique of Vaginoplasty Developing Normal Vagina, Role of Stemness Markers and Translational Genes.

AIMS AND OBJECTIVES: To study development of neo-vagina by metaplastic conversion of peritoneum, To identify translational Stemness markers using NANOG/OCT4/SOX2 from serial neo-vaginal mRNA, cDNA and to study role of WNT and HOXA genes in patients undergoing vaginoplasty. MATERIAL AND METHODS: 75 MRKH Syndrome women underwent laparoscopic peritoneal vaginoplasty (LPV). Two patients underwent serial neo-vaginal biopsies on day 0, 7-9, 12-14, 21 and 33. Fifteen MRKHS and twelve controls were subjected for neo-vaginal biopsy to detect genes upregulation. Remaining patients were evaluated anatomically and functionally. RESULTS: The translational stemness markers NANOG, OCT4 and SOX2 responsible for neo-vaginal formation were identified. Their appearance, concentration at different stages of conversion were demonstrated. The neo-vagina has shown up-regulation of these translational stemness markers. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. In the subjects stemness markers (NANOG, OCT4 and SOX2) appeared from day 9 to 14 of the neo-vaginal biopsies and after achieving the peak declined later. Genetic analysis showed low values in HOXA 9,10,11,13 and up-regulation of WNT 4A,5A,7 genes in neo-vagina. CONCLUSIONS: Study shows peritoneal metaplastic conversion to normal vagina, identified the translational stemness markers and genes responsible. The neo-vagina has shown up-regulation of these genes. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. Furthering this research, activating these genes may lead to treatment of developmental defects of Mullerian duct, obviating the need of transplant.

Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

BACKGROUND: Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA. MATERIALS AND METHODS: The study was performed in male swiss mice (20+/-2 g) using single-cell gel electrophoresis and a peripheral blood micronucleus assay. ASA and TSA (5, 10 or 20 mg/kg) were administered 15 minutes after MMC (1 mg/kg) once daily for 3 or 7 days. RESULTS: Both ASA and TSA significantly decreased the DNA damage induced by MMC as indicated by a decrease in the comet parameters in bone marrow cells and decreased frequencies of micronucleated reticulocytes in peripheral blood. CONCLUSION: The results clearly demonstrate the anti-genotoxic potential of ASA and TSA.