Natural radioactivity distribution in geological matrices around Kaiga environment

Summary The activity and absorbed dose rate of the naturally occurring radionuclides, viz. ²³⁸U, ²³² Th and ⁴⁰K were determined in soil and rock samples collected around Kaiga site. The mean activity levels (Kaiga soil) of naturally occurring ²³² Th are comparable with that in worldwide soil, while concentrations of ²³⁸U and ⁴⁰K are lower than those in worldwide soil. The absorbed dose rate in outdoor air ranged 20-58 nGy ^. h^-1 with a mean of 33.3 nGy ^. h^-1, which is below the world average of 60 nGy ^. h^-1. The total effective dose rate in outdoor air for soils ranged 25.6-74.4 mSv ^. y^-1 with a mean of 43.0 mSv ^. y^-1. The estimated dose rate at Kaiga is comparable with that estimated at Kakrapar and Rawatbhata and much less than that estimated at coastal sites of India.     

Construction of 4D-QSAR Models for Use in the Design of Novel p38-MAPK Inhibitors

The p38-mitogen-activated protein kinase (p38-MAPK) plays a key role in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) release during the inflammatory process, emerging as an attractive target for new anti-inflammatory agents. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis [Hopfinger et al., J. Am. Chem. Soc., 119 (1997) 10509] was applied to a series of 33 (a training set of 28 and a test set of 5) pyridinyl-imidazole and pyrimidinyl-imidazole inhibitors of p38-MAPK, with IC50 ranging from 0.11 to 2100 nM [Liverton et al., J. Med. Chem., 42 (1999) 2180]. Five thousand conformations of each analogue were sampled from a molecular dynamics simulation (MDS) during 50 ps at a constant temperature of 303 K. Each conformation was placed in a 2 angstroms grid cell lattice for each of three trial alignments. 4D-QSAR models were constructed by genetic algorithm (GA) optimization and partial least squares (PLS) fitting, and evaluated by leave-one-out cross-validation technique. In the best models, with three to six terms, the adjusted cross-validated squared correlation coefficients, Q2adj, ranged from 0.67 to 0.85. Model D (Q2adj = 0.84) was identified as the most robust model from alignment 1, and it is representative of the other best models. This model encompasses new molecular regions as containing pharmacophore sites, such as the amino-benzyl moiety of pyrimidine analogs and the N1-substituent in the imidazole ring. These regions of the ligands should be further explored to identify better anti-inflammatory inhibitors of p38-MAPK.     

Intramolecular 1,3-dipolar cycloaddition of cyclo-1,3-diene-tethered nitrile oxides

Intramolecular 1,3-dipolar cycloaddition of cyclo-1,3-diene- and -1,3,5-triene-tethered nitrile oxides gave tricyclic isoxazolines as a single stereoisomer in most cases. The relative stereochemistry of tricycle-fused isoxazolines resulting from 1,3-dipolar cycloaddition of cyclo-1,3-diene-tethered nitrile oxides is cis-cis, whereas from cyclohepta-1,3,5-triene-tethered nitrile oxides the cis-trans isomer predominates.     

Kinetics of substitution of aquo ligands fromcis-diaquo-bis-(biguanide) cobalt(III) and chromium(III) ions by aspartic acid in ethanol—water mixtures

The kinetics of substitution of aqua ligands fromcis-diaqua-bis(biguanide)cobalt(III) and chromium(III) ions by aspartic acid in EtOH–H₂O media have been studied spectrophotometrically in the 30 to 45°C range. We propose the following rate law for the anation

The circular chemistry conceptual framework: A way forward to sustainability in industry 4.0

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Synthesis of Monosaccharide‐Derived Spirocyclic Cyclopropylamines and Their Evaluation as Glycosidase Inhibitors

The glucose‐, mannose‐, and galactose‐derived spirocyclic cyclopropylammonium chlorides 1a – 1d, 2a – 2d and 3a – 3d were prepared as potential glycosidase inhibitors. Cyclopropanation of the diazirine 5 with ethyl acrylate led in 71% yield to a 4 : 5 : 1 : 20 mixture of the ethyl cyclopropanecarboxylates 7a – 7d , while the Cu‐catalysed cycloaddition of ethyl diazoacetate to the exo‐glycal 6 afforded 7a – 7d (6 : 2 : 5 : 3) in 93–98% yield (Scheme 1). Saponification, Curtius degradation, and subsequent addition of BnOH or t‐BuOH led in 60–80% overall yield to the Z‐ or Boc‐carbamates 11a – 11d and 12a – 12d , respectively. Hydrogenolysis of 11a – 11d afforded 1a – 1d , while 12a – 12d was debenzylated to 13a – 13d prior to acidic cleavage of the N‐Boc group. The manno‐ and galacto‐isomers 2a – 2d and 3a – 3d , respectively, were similarly obtained in comparable yields (Schemes 2 and 4). Also prepared were the differentially protected manno‐configured esters 24a – 24d ; they are intermediates for the synthesis of analogous N‐acetylglucosamine‐derived cyclopropanes (Scheme 3). The cyclopropylammonium chlorides 1a – 1d, 2a – 2d and 3a – 3d are very weak inhibitors of several glycosidases (Tables 1 and 2). Traces of Pd compounds, however, generated upon catalytic debenzylation, proved to be strong inhibitors. PdCl is, indeed, a reversible, micromolar inhibitor for the β‐glucosidases from C. saccharolyticum and sweet almonds (non‐competitive), the β‐galactosidases from bovine liver and from E. coli (both non‐competitive), the α‐galactosidase from Aspergillus niger (competitive), and an irreversible inhibitor of the α‐glucosidase from yeast and the α‐galactosidase from coffee beans. The cyclopropylamines derived from 1a – 1d or 3a – 3d significantly enhance the inhibition of the β‐glucosidase from C. saccharolyticum by PdCl , lowering the K_i value from 40 μM (PdCl ) to 0.5 μM for a 1 : 1 mixture of PdCl and 1d . A similar effect is shown by cyclopropylamine, but not by several other amines.     

Kinetics and mechanism of the oxidation of thiosulphate by hexachloroplatinate(IV)

Summary Rate constants for the oxidation of thiosulphate by hexachloroplatinate(IV) have been measured. The kinetics of the oxidation of thiosulphate follow a second-order rate law, first order with respect to thiosulphate and first order with respect to platinum(IV). The influence of pH is small. The rates are found to depend on the nature and concentration of the cations and follow the order: Cs⁺>Rb⁺>K⁺>Na⁺>Li⁺. The activation parameters calculated from the temperature studies are: H=42.9 k J mol^–1 and S=–102 JK^–1 mol^–1. A mechanism of the reaction in terms of intermediate formation of free radicals followed by the formation of tetrathionate is postulated to explain the kinetic behaviour.     

Methyl rotational tunneling dynamics of p-xylene confined in a crystalline zeolite host

The methyl rotational tunneling spectrum of p-xylene confined in nanoporous zeolite crystals has been measured by inelastic neutron scattering (INS) and proton nuclear magnetic resonance (NMR), and analyzed to extract the rotational potential energy surfaces characteristic of the methyl groups in the host-guest complex. The number and relative intensities of the tunneling peaks observed by INS indicate the presence of methyl-methyl coupling interactions in addition to the methyl-zeolite interactions. The INS tunneling spectra from the crystals (space group P2(1)2(1)2(1) with four crystallographically inequivalent methyl rotors) are quantitatively interpreted as a combination of transitions involving two coupled methyl rotors as well as a transition involving single-particle tunneling of a third inequivalent rotor, in a manner consistent with the observed tunneling energies and relative intensities. Together, the crystal structure and the absence of additional peaks in the INS spectra suggest that the tunneling of the fourth inequivalent rotor is strongly hindered and inaccessible to INS measurements. This is verified by proton NMR measurements of the spin-lattice relaxation time which reveal the tunneling characteristics of the fourth inequivalent rotor.     

In vitro and in vivo investigations on the photodynamic activity of core-modified expanded porphyrin--ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin

The core modification of expanded porphyrins has been proved to have better photochemical properties, which are favorable for photodynamic therapy (PDT) applications. In this context, this study was aimed to investigate the in vitro and in vivo photodynamic activity of one such core-modified expanded porphyrin, namely, ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin. For the in vitro studies, human erythrocytes were used as a membrane semimodel system to investigate the partitioning ability and drug-uptake characteristics. The partition studies on the membrane semimodel system revealed that maximum partitioning occurs at 12 microgm/mL concentration, and from the drug-uptake studies it is observed that maximum amount of the sensitizer is bound to the erythrocyte membranes during a 45 min incubation period. Photohemolysis studies at different concentrations of the sensitizer and exposure time showed maximum damage at 5 microgm/mL and 30 min exposure time. In vivo studies were performed on 7,12-dimethylbenz(a)nthracene-induced superficial squamous cell carcinoma on mouse skin. The sensitizer at a concentration of 2.5% in 2.0% dimethyl sulfoxide was applied topically on the tumor spot. After 1 h incubation the tumor spot was exposed to laser irradiation from Nd-YAG laser at its second harmonic wavelength of 532 nm. The photodynamic efficacy was estimated by tumor volume measurements at regular intervals after the treatment. One month after PDT exposure a 3.9-fold decrease in the tumor volume was observed with respect to the tumor volume before treatment. The treatment efficacy was further confirmed by histological and fluorescence spectroscopic evaluations of the tissue biopsy sample from the treated area. The results of our study suggest that the ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin may find possible applications in the new modality of cancer treatment.