A Simple Manganese(I) Catalyst for the Efficient and Selective Hydrophosphination of Olefins with PH3, Primary, and Secondary Phosphanes.

A tridentate ligand L with a P,NH,N donor motif was synthesized in few steps from commercially available precursors. Upon reaction with [MnBr(CO)5], an octahedral 18-electron complex [Mn(CO)3(L)]Br (1) is obtained in which L adopts a facial arrangement. After deprotonation of the NH group in the cationic complex unit, a neutral Mn(I) amido complex [Mn(CO)2(L-H)] (2) is formed under loss of CO. Rearrangement of L-H leads to a trigonal bipyramidal structure in which the P and N donor centers are in trans position. Further deprotonation of 2 results in a dep-blue anionic complex fragment [Mn(CO)2(L-2H)]- (3). DFT calculations and a QTAIM analysis show that the amido complex 2 contains a Mn-N bond with partial double bond character and 3 an aromatic MnN2C2 ring. The anion [Mn(CO)2(L-2H)]- reacts with Ph2PH to give a phosphido complex, which serves as phosphide transfer reagent to activated olefins. But the catalytic activity is low. However, the neutral amido complex 2 is an excellent catalyst and with loadings as low as 0.04 mol %, turn over frequencies of >40'000 h-1 can be achieved. Furthermore, secondary and primary alkyl phosphines as well as PH3 can be added in a catalytic hydrophosphination reaction to a wide range of activated olefins such as α,ß-unsaturated aldehydes, ketones, esters, and nitriles. But also, vinyl pyridine and some styrene derivatives are converted into the corresponding phosphanes.

Importance of tautomerism in drugs.

Tautomerism is an important phenomenon exhibited by many drugs. As we discuss in this review, identifying the different tautomers of drugs and exploring their importance in the mechanisms of drug action are integral components of current drug discovery. Nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), Raman, and terahertz spectroscopic techniques, as well as X-ray diffraction, are useful for exploring drug tautomerism. Quantum chemical methods, in association with pharmacoinformatics tools, are being used to evaluate tautomeric preferences in terms of energy effects. Desmotropy (i.e., tautomeric polymorphism) of the drugs is particularly important in drug delivery studies.

Tuning of (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene nanostructures for the selective detection of imidacloprid.

The present work demonstrates a facile route for synthesizing the organic nanoparticles (ONPs) and the blue fluorescent Quantum Dots (QDs) based on an organic molecule named (E)-(4-fluorophenyl)-1,1-diamino-2,3-diazabuta-1,3-diene. The synthesis process possesses advantages viz green synthesis, non-toxic degraded products, and amount of organic compound. Initially, the ONPs were prepared using the nanoprecipitation method and were screened for their recognition potential against various pesticides, however, no selectivity has been observed. This motivated us to tune the ONPs into QDs. The QDs were prepared using the hydrothermal method and a color change was observed in the QDs solution under daylight and under a UV lamp. The emission wavelength was observed at 400 nm (λexcitation = 278 nm). The synthesized QDs exhibited selective sensing potential towards imidacloprid via a quenching mechanism. A normalised decrement in the luminescence intensity of QDs was observed on raising the concentration of imidacloprid and a good linear response was noticed over a concentration varies from 1 µM to 100 µM with a regression coefficient of 0.99. The detection limit was estimated to be 4.53 nM and quantification limit was calculated to be and 13.72 nM.

1,1-Diaminoazines as organocatalysts in phospha-Michael addition reactions.

1,1-Diaminoazines can act as effective organocatalysts for the formation of phosphorus-carbon bonds between biphenylphosphine oxide and an activated alkene (Michael acceptor). These catalysts provide the P-C adducts at a faster rate and with relatively better yields in comparison to the organocatalysts employed earlier. The notable advantage is that 1,1-diaminoazines catalyse the reaction even in an aqueous medium with very good yields. Organocatalysis using 1,1-diaminoazines was also successfully carried out between dimethylphosphite and benzylidenemalononitrile under multicomponent conditions.

Synthesis of 1,4-dihydropyrazolo[4,3-b]indoles via intramolecular C(sp2)-N bond formation involving nitrene insertion, DFT study and their anticancer assessment.

We herein report a new synthetic route for a series of unreported 1,4-dihydropyrazolo[4,3-b]indoles (6-8) via deoxygenation of o-nitrophenyl-substituted N-aryl pyrazoles and subsequent intramolecular (sp2)-N bond formation under microwave irradiation expedite modified Cadogan condition. This method allows access to NH-free as well as N-substituted fused indoles. DFT study and controlled experiments highlighted the role of nitrene insertion as one of the plausible reaction mechanisms. Furthermore, the target compounds exhibited cytotoxicity at low micromolar concentration against lung (A549), colon (HCT-116), and breast (MDA-MB-231, and MCF-7) cancer cell lines, induced the ROS generation and altered the mitochondrial membrane potential of highly aggressive MDA-MB-231 cells. Further investigations revealed that these compounds were selective Topo I (6h) or Topo II (7a, 7b) inhibitors.

Iodine Catalyzed Oxidative Coupling of Diaminoazines and Amines for the Synthesis of 3,5-Disubstituted-1,2,4-Triazoles.

A simple, convenient, transition metal-free one pot synthesis of 3,5-disubstituted-1,2,4-triazoles has been established. The innovation in this reaction is the use of easily available 1,1-diaminoazines as substrates. This method provides the products with wider substrate scope, at an expedited rate, and with relatively better yields in comparison to the reported methods. The reaction mechanism involves an initial intermolecular nucleophilic addition (facilitated by I2) followed by intramolecular nucleophilic cyclization.

Synthesis of N-substituted indole derivatives as potential antimicrobial and antileishmanial agents.

Leishmaniasis and microbial infections are two of the major contributors to global mortality and morbidity rates. Hence, development of novel, effective and safer antileishmanial and antimicrobial agents having reduced side effects are major priority for researchers. Two series of N-substituted indole derivatives i.e. N-substituted indole based chalcones (12a-g) and N-substituted indole based hydrazide-hydrazones (18a-g, 19a-f, 21 a-g) were synthesized. The synthesized compounds were characterized by 1H NMR, 13C NMR, Mass and FT-IR spectral data. Further these derivatives were evaluated for their antimicrobial potential against Escherichia coli, Bacillus subtilis, Pseudomonas putida and Candida viswanathii, and antileishmanial potential against promastigotes of Leishmania donovani. Compounds 18b, 18d and 19d exhibited significant activity with an IC50 of 0.19 ± 0.03 µM, 0.14 ± 0.02 µM and 0.16 ± 0.06 µM against B. subtilis which was comparable to chloramphenicol (IC50 of 0.25 ± 0.03 µM). Compounds 12b and 12c exhibited an IC50 of 24.2 ± 3.5 µM and 21.5 ± 2.1 µM in the antileishmanial assay. Binding interactions of indole based hydrazide-hydrazones were studied with nitric oxide synthase in silico in order to understand the structural features responsible for activity.

Characterization of Photodegradation Products of Bepotastine Besilate and In Silico Evaluation of Their Physicochemical, Absorption, Distribution, Metabolism, Excretion and Toxicity Properties.

Bepotastine (BPT) is a H1-receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis and orally for the treatment of allergic rhinitis and urticaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding 5 photodegradation products. The structures of the latter were elucidated from data generated by liquid chromatography-high-resolution mass spectrometry and multistage mass spectrometry. Of the 5, 4 products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density functional theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion, and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor™ software.

LC-ESI-QTOF-MS analysis utilizing gas-phase fragmentation reactions subjected to ESI-IS-CID and ESI-CID-MS/MS conditions to study the degradation behaviour of sorafenib tosylate: NMR and in vitro cytotoxicity and apoptosis detection studies of hydrolytic degradation products.

The present study was to investigate the degradation profile of sorafenib tosylate (SORA), a potent oral multi-kinase inhibitor under various stress conditions as per ICH (Q1A (R2)) guidelines. Separation of SORA and its degradation products (DP-1-DP-5) was achieved on Acquity UPLC BEH C18 (100 mm × 2.1 mm × 1.7 µm) column using a gradient elution of 0.1% formic acid and acetonitrile at a flow rate of 0.3 mL/min within 12 min. High resolution quadruple time-of-flight mass spectrometer (Q-TOF/MS) was utilized for characterization of all DPs. In ESI/CID-MS/MS experiments, the protonated DP-1 and DP-2 exhibited few interesting product ions which provide a compelling evidence for the compounds to undergo gas phase rearrangement reaction justified by its mechanistic explanation in support with density functional theory (DFT). In-source collision-induced dissociation (IS-CID) fragmentation using ESI/APCI-MS analysis exhibited the formation of N-deoxygenated product ion peak corresponds to pyridine N-oxide moiety as in DP-5. Further, major hydrolytic DPs (DP-2 and DP-3) were isolated on preparative HPLC and structural elucidation was done using ID NMR (1H, 13C and DEPT-135) experiments. In vitro cytotoxicity study for SORA and its isolated DPs were assessed by observing morphological changes in HepG2 cell lines under phase-contrast microscopy and MTT assay. Taken together, it was known that DP-2 and DP-3 were less potent with a cell viability of more than 90% and IC50 >50 µM in comparison with SORA (IC50 = 2.99 ±â€¯0.35 µM). The developed method was validated in terms of specificity, limit of detection, limit of quantification, linearity, accuracy, precision and robustness.

An unprecedented N- to C-sulfonyl migration in the reaction of azomethine amine and allenoates: access to arylsulfonylmethyl substituted pyrazolo[1,5-c]quinazoline and mechanistic studies.

A serendipitous discovery of [1,3]-sulfonyl migration has been made in the two-component reaction of azomethine imine and allenoates. Current methodology involving N-S bond cleavage and C-S bond formation provided easy access to biologically important arylsulfonylmethyl substituted pyrazolo[1,5-c]quinazolines. Subsequently, a one-pot sequential protocol has been developed from the easily available starting material. The mechanistic investigation using quantum chemical methods revealed that the sulfonyl migration step is a concerted [1,3]-sigmatropic shift.

Azines: synthesis, structure, electronic structure and their applications.

Azines are organic molecules which bear the C[double bond, length as m-dash]N-N[double bond, length as m-dash]C functional unit. In the recent past, azines have received increased attention due to the recognition of their biological, chemical and materials properties. Azines have been conventionally synthesised by the condensation of hydrazine with ketones and aldehydes, and many alternate routes are also available. Azines have been extensively studied to investigate the presence or absence of conjugation with the help of computational studies and crystal structure analysis owing to their importance in nonlinear optics. The tautomerism in azines is a topic of contemporary interest. Herein, we present a review of recent advances in the structure and electronic structure properties of azines along with information on the modern methods of their synthesis and application as precursors in generating heterocycles in organic synthesis and in medicinal chemistry. A few applications of azines in the field of materials chemistry in developing metal-organic frameworks (MOFs), covalent organic frameworks (COFs), energetic materials and chemosensors are also included.

Stability behaviour of antiretroviral drugs and their combinations. 10: LC-HRMS, LC-MSn, LC-NMR and NMR characterization of fosamprenavir degradation products and in silico determination of their ADMET properties.

The present study focused upon the forced degradation behaviour of fosamprenavir (FPV), an antiretroviral drug. A total of six degradation products (DPs) were separated on a non-polar stationary phase by high performance liquid chromatography (HPLC). For the characterization, comprehensive mass fragmentation pathway of the drug was initially established using high resolution mass spectrometry (HRMS) and multi-stage tandem mass spectrometry (MSn) data. Subsequently, LC-HRMS and LC-MSn studies were carried out on the forced degraded samples containing the DPs. Five DPs were isolated and subjected to extensive 1D (1H, 13C, and DEPT-135 (distortionless enhancement by polarization)) and 2D (COSY (correlation spectroscopy), TOCSY (total correlation spectroscopy), HSQC (heteronuclear single quantum coherence) and HMBC (heteronuclear multiple bond correlation)) nuclear magnetic resonance (NMR) studies to ascertain their structures, while one degradation product was subjected to LC-NMR studies, as it could not be isolated. The collated information was helpful in characterization of all the DPs, and to delineate the degradation pathway of the drug. Additionally, physicochemical, as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the drug and its DPs were evaluated in silico by ADMET Predictor™ software.

Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae.

Two new compounds, lasdiplactone (1) and lasdiploic acid (2) and one known compound 3 were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structures of new compounds were determined by interplay of spectral techniques (IR, mass, 1H NMR, 13C NMR, DEPT, and 2D NMR). The absolute configuration at C-4 position of 1 was established as S using a process similar to modified Mosher's method. The absolute configuration of 2 was established by comparing its ECD spectrum with the calculated ECD spectra of all possible isomers. In the in vitro XO inhibition assay, the highest inhibition was exhibited by 3 with an IC50 of 0.38 ±â€¯0.13 µg/ml, followed by 2 with an IC50 of 0.41 ±â€¯0.1 µg/ml and the least in 1. The oxidized form of 1 also showed high XO inhibition with IC50 of 0.35 ±â€¯0.13 µg/ml.

Unanticipated Cleavage of 2-Nitrophenyl-Substituted N-Formyl Pyrazolines under Bechamp Conditions: Unveiling the Synthesis of 2-Aryl Quinolines and Their Mechanistic Exploration via DFT Studies.

We herein report for the first time an unusual decomposition of 2-nitrophenyl-substituted N-formyl pyrazolines under Bechamp reduction condition employed to yield 2-aryl quinolines exclusively instead of pyrazolo[1,5-c]quinazolines. The reaction investigation suggests acid-mediated cleavage of 1 followed by a retro-Michael addition, and a subsequent in situ intramolecular reductive cyclization through a modified Friedlander mechanism afforded 2-aryl quinolines (2) in good yields. The proposed mechanistic pathways were supported via experimental evidence and density functional theory studies. B3LYP/6-31+G(d) analysis indicated the involvement of trans-2-hydroxyaminochalcone as a key intermediate and its isomerization and cyclization, leading to unusual product formation.