Positron annihilation lifetime studies of free volume in a polymer electrolyte PEO complexed with NH4I

Positron lifetime spectroscopy has been applied to study the temperature dependence of free-volume properties in a solvent-free polymer–salt complex polyethylene oxide (PEO) doped with ammonium iodide (NH₄I, with NH ≈ 0.076) in the temperature range of 298–353 K. The observed lifetime spectra were resolved into three components and the longest lifetime, τ₃, was associated with the pick-off annihilation of ortho-positronium (o-Ps) trapped by the free volume. The lifetime component, τ₃, and its intensity, I₃, both showed a significant variation with temperature, which followed a different course in the heating and cooling cycle. Changes in the temperature coefficient of τ₃ and I₃ were observed at T ≈ 328 K, the melting point of the sample. This behaviour is correlated to the temperature variation of the electrical conductivity. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36: 969–976, 1998     

Protein surface-assisted enhancement in the binding affinity of an inhibitor for recombinant human carbonic anhydrase-II

We elaborate on a novel strategy for enhancing the binding affinity of an active-site directed inhibitor by attaching a tether group, designed to interact with the surface-exposed histidine residue(s) of enzymes. In this approach, we have utilized the recombinant form of human carbonic anhydrase-II (hCA-II) as the enzyme source and benzenesulfonamide and its derivatives as inhibitors. The steady-state kinetic and the ligand binding data revealed that the attachment of iminodiacetate (IDA)-Cu(2+) to benzenesulfonamide (via a triethylene glycol spacer) enhanced its binding affinity for hCA-II by about 40-fold. No energetic contribution of either IDA or triethylene glycol spacer was found (at least in the ground state of the enzyme-inhibitor complex) when Cu(2+) was stripped off from the tether group-conjugated sulfonamide derivative. Arguments are presented that the overall strategy of enhancing the binding affinities of known inhibitors by attaching the IDA-Cu(2+) groups to interact with the surface-exposed histidine residues will find a general application in designing the isozyme-specific inhibitors as potential drugs.     

Two-prong inhibitors for human carbonic anhydrase II

The enzyme inhibitors are usually designed by taking into consideration the overall dimensions of the enzyme's active site pockets. This conventional approach often fails to produce desirable affinities of inhibitors for their cognate enzymes. To circumvent such constraints, we contemplated enhancing the binding affinities of inhibitors by attaching tether groups, which would interact with the surface exposed amino acid residues. This strategy has been tested for the inhibition of human carbonic anhydrase II. Benzenesulfonamide serves as a weak inhibitor for the enzyme, but when it is conjugated to iminodiacetate-Cu2+ (which interacts with the surface-exposed His residues) via a spacer group, its binding affinity is enhanced by about 2 orders of magnitude. This "two-prong" approach is expected to serve as a general strategy for converting weak inhibitors of enzymes into tight-binding inhibitors.     

Synthesis, characterisation and catalytic activities of manganese(III) complexes of pyridoxal-based ONNO donor tetradenatate ligands

Reaction of Mn^II(CH₃COO)₂ with dibasic tetradentate ligands, N,N′-ethylenebis(pyridoxylideneiminato) (H₂pydx-en, I), N,N′-propylenebis(pyridoxylideneiminato) (H₂pydx-1,3-pn, II) and 1-methyl-N,N′-ethylenebis(pyridoxylideneiminato) (H₂pydx-1,2-pn, III) followed by aerial oxidation in the presence of LiCl gives complexes [Mn^III(pydx-en)Cl(H₂O)] (1) [Mn^III(pydx-1,3-pn)Cl(CH₃OH)] (2) and [Mn^III(pydx-1,2-pn)Cl(H₂O)] (3), respectively. Crystal and molecular structures of [Mn(pydx-en)Cl(H₂O)] (1) and [Mn(pydx-1,3-pn)Cl(CH₃OH)] (2) confirm their octahedral geometry and the coordination of ligands through ONNO(2-) form. Reaction of manganese(II)-exchanged zeolite-Y with these ligands in refluxing methanol followed by aerial oxidation in the presence of NaCl leads to the formation of the corresponding zeolite-Y encapsulated complexes, abbreviated herein as [Mn^III(pydx-en)]-Y (4), [Mn^III(pydx-1,3-pn)]-Y (5) and [Mn^III(pydx-1,2-pn)]-Y (6). These encapsulated complexes are used as catalysts for the oxidation, by H₂O₂, of methyl phenyl sulfide, styrene and benzoin efficiently. Oxidation of methyl phenyl sulfide under the optimized reaction conditions gave ca. 86% conversion with two major products methyl phenyl sulfoxide and methyl phenyl sulfone in the ca. 70% and 30% selectivity, respectively. Oxidation of styrene catalyzed by these complexes gave at least five products namely styrene oxide, benzaldehyde, benzoic acid, 1-phenylethane-1,2-diol and phenylacetaldehyde with a maximum of 76.9% conversion of styrene by 4, 76.3% by 5 and 76.0% by 6 under optimized conditions. The selectivity of the obtained products followed the order: benzaldehyde > benzoic acid > styrene oxide > phenylacetaldehyde > 1-phenylethane-1,2-diol. Similarly, ca. 93% conversion of benzoin was obtained by these catalysts, where the selectivity of the products followed the order benzil > benzoic acid > benzaldehyde-dimethylacetal. Tests for the recyclability and heterogeneity of the reactions have also been carried. Neat complexes are equally active. However, the recycle ability of encapsulated complexes makes them better over neat ones.     

Trichosanthes dioica root possesses stimulant laxative activity in mice

Trichosanthes dioica Roxb. (Cucurbitaceae), named 'pointed gourd' in English, is a dioecious climber grown in India. This study was aimed at evaluating the laxative activity of the aqueous extract of T. dioica root (TDA) in Swiss albino mice. The laxative activity of TDA (100 and 200?mg?kg(-1) body weight per os) was evaluated by assessing the excretory bowel activities in naive (non-constipated) and in drug (loperamide)-induced constipation in mice. Further, the gastrointestinal transit was measured in both naive and in constipated mice. Castor oil (0.5?mL/mouse per os) was used as the reference. TDA significantly and dose-dependently increased all the excretory bowel activities and gastrointestinal transit in both naive and constipated mice. TDA at 200?mg?kg(-1) body weight was found to be the most active, causing diarrhoea in mice. Thus, T. dioica root demonstrated stimulant laxative activity in Swiss mice, validating its traditional usage in India.     

Cleavable cationic antibacterial amphiphiles: synthesis, mechanism of action, and cytotoxicities

The development of novel antimicrobial agents having high selectivity toward bacterial cells over mammalian cells is urgently required to curb the widespread emergence of infectious diseases caused by pathogenic bacteria. Toward this end, we have developed a set of cationic dimeric amphiphiles (bearing cleavable amide linkages between the headgroup and the hydrocarbon tail with different methylene spacers) that showed high antibacterial activity against human pathogenic bacteria (Escherichia coli and Staphylococcus aureus) and low cytotoxicity. The Minimum Inhibitory Concentrations (MIC) were found to be very low for the dimeric amphiphiles and were lower or comparable to the monomeric counterpart. In the case of dimeric amphiphiles, MIC was found to decrease with the increase in the spacer chain length (n = 2 to 6) and again to increase at higher spacer length (n > 6). It was found that the compound with six methylene spacers was the most active among all of the amphiphiles (MICs = 10-13 μM). By fluorescence spectroscopy, fluorescence microscopy, and field-emission scanning electron microscopy (FESEM), it was revealed that these cationic amphiphiles interact with the negatively charged bacterial cell membrane and disrupt the membrane integrity, thus killing the bacteria. All of the cationic amphiphiles showed low hemolytic activity (HC(50)) and high selectivity against both gram-positive and gram-negative bacteria. The most active amphiphile (n = 6) had a 10-13-fold higher HC(50) than did the MIC. Also, this amphiphile did not show any cytotoxicity against mammalian cells (HeLa cells) even at a concentration above the MIC (20 μM). The critical micellar concentration (CMC) values of gemini surfactants were found to be very low (CMC = 0.30-0.11 mM) and were 10-27 times smaller than the corresponding monomeric analogue (CMC = 2.9 mM). Chemical hydrolysis and thermogravimetric analysis (TGA) proved that these amphiphiles are quite stable under both acidic and thermal conditions. Collectively, these properties make the newly synthesized amphiphiles potentially superior disinfectants and antiseptics for various biomedical and biotechnological applications.     

Formation of fully pearlitic microstructure in medium carbon steel

Pearlitic microstructure can be obtained when austenite of eutectoid composition is slowly cooled from high temperature to below the Ae₃ temperature. It is also possible to induce such structure in hypo-eutectoid composition of austenite through proper heat treatment as well. However, in the current work, one hypo-eutectoid steel during very slow cooling only produced completely pearlitic microstructure which was not expected from a steel with such composition. The calculations carried out considering orthoequilibrium condition actually predicted the presence of about 37% ferrite in the microstructure. Further calculations considering different equilibrium modes and kinetics of transformation indicates that the composition and thermal condition of the steel under consideration was such that proeutectoid ferrite formation could not start before the composition reaches to the Negligible Partitioning Local Equilibrium phase boundary which further coincides with the area described by Hultgren extrapolation and thus, the steel completely transforms to pearlite even with hypo-eutectoid composition during very slow cooling.     

Equivalence of the train model of earthquake and boundary driven Edwards-Wilkinson interface

A discretized version of the Burridge-Knopoff train model with (non-linear friction force replaced by) random pinning is studied in one and two dimensions. A scale free distribution of avalanches and the Omori law type behaviour for after-shocks are obtained. The avalanche dynamics of this model becomes precisely similar (identical exponent values) to the Edwards-Wilkinson (EW) model of interface propagation. It also allows the complimentary observation of depinning velocity growth (with exponent value identical with that for EW model) in this train model and Omori law behaviour of after-shock (depinning) avalanches in the EW model.     

Photoimmunomodulation and melatonin

The seasons, and daily physical rhythms can have a profound effect on the physiology of the living organism, which includes immune status. The immune system can be influenced by a variety of signals and one of them is photic stimulus. Light may regulate the immunity through the neuroendocrine system leading to the most recent branch of research the “Photoimmunomodulation”. Mammals perceive visible light (400–700 nm) through some specialized photoreceptors located in retina like retinal ganglion cells (RGC). This photic signal is then delivered to the visual cortex from there to the suprachiasmatic nucleus (SCN) of the hypothalamic region. Melatonin – one of the universally accepted chronobiotic molecule secreted by the pineal gland is now emerging as one of the most effective immunostimulatory compound in rodents and as oncostatic molecule at least in human. Its synthesis decreases with light activation along with norepinephrine and acetylcholine. The changes in level of melatonin may lead to alterations (stimulatory/inhibitory) in immune system. The evidences for the presence of melatonin receptor subtypes on lymphoid tissues heralded the research area about mechanism of action for melatonin. Further, melatonin receptor subtypes-MT1 and MT2 was noted on pars tuberalis, SCN and on lymphatic tissues suggesting a direct action of melatonin in modulation of immunity by photoperiod as well. The nuclear receptors (ROR, RZR etc.) of melatonin are known for its free radical scavenging actions and might be indirectly controlling the immune function.     

Antiferromagnetic porous metal-organic framework containing mixed-valence [Mn(II)4Mn(III)2(μ4-O)2]10+ units with catecholase activity and selective gas adsorption

A multifunctional porous metal organic framework based on mixed-valence hexa-nuclear [Mn(III)(2)Mn(II)(4)O(2)(pyz)(2)(C(6)H(5)CH(2)COO)(10)] (pyz = pyrazine) units has been synthesized. The complex has been characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction analysis, and variable-temperature magnetic measurements. The structural analysis reveals that the bidentate pyz molecules connect each [Mn(6)] unit to its four [Mn(6)] neighbors through the peripheral Mn(II) centers, giving rise to a three-dimensional (3D) distorted diamond-like porous framework. Variable-temperature (2-300 K) magnetic susceptibility measurements show the presence of dominant antiferromagnetic interactions within the discrete [Mn(6)] cluster that have been fitted with a model containing three exchange constants developed for the complex (J(1) = -8.6 cm(-1), J(2) = -3.9 cm(-1), and J(3) = -100.0 cm(-1)). Using 3,5-di-tert-butyl catechol (3,5-DTBC) as the substrate, catecholase activity of the complex has been studied; the turn over number is determined to be of 2547 h(-1) in acetonitrile. This porous compound shows remarkable selectivity for adsorption of CO(2) over N(2) that may be correlated with the effect of window flexibility of the pore to the corresponding adsorbate molecules.