Adsorption isotherms for neutral organic compounds-A hierarchy in modelling: Part III

A simple three-state model permitting two different configurational states for the solvent, together with one for the organic adsorbate, is analysed to derive the adsorption isotherm. The implications of this model regarding pseudo-two-state and pseudo-Frumkin adsorption isotherms are indicated. A critique of the earlier theory of Bockris, Devanathan and Müller is presented in brief.

Adsorption isitherms for neutral organic compounds-A hierarchy in modelling: Part IV. Charge of maximum adsorption-Statistical mechanical basis

The charge at which adsorption of orgamc compounds attains a maximum ( \sigma MAX M) at an electrochenucal interface is analysed using several multi-state models in a hierarchical manner The analysis is based on statistical mechamcal results for the following models (A) two-state site parity, (B) two-state muhl-slte, and (C) three-state site parity The coulombic interactions due to permanent and reduced dipole effects (using mean field approximation), electrostatic field effects and specific substrate interactions have been taken into account. The simplest model in the hierarchy (two-state site parity) yields the exphcit dependence of ( \sigma MAX M) on the permanent dipole moment, polarizability of the solvent and the adsorbate, lattice spacing, effective coordination number, etc Other models in the baerarchy bring to hght the influence of the solvent structure and the role of substrate interactions, etc As a result of this approach, the "composition" of oM.x m terms of the fundamental molecular constants becomes clear. With a view to use these molecular results to maxamum advantage, the derived results for ( \sigma MAX M) have been converted into those involving experimentally observable parameters lake Co, C 1, E N, etc Wherever possible, some of the earlier phenomenologlcal relations reported for ( \sigma MAX M), notably by Parsons, Damaskm and Frumkln, and Trasattl, are shown to have a certain molecular basis, vlz a simple two-state sate panty model.As a corollary to the hxerarcbacal modelling, \sigma MAX M and the potential corresponding to at (Emax) are shown to be constants independent of 0max or Corg for all models The lmphcatlon of our analysis f o r OmMa x with respect to that predicted by the generalized surface layer equation (which postulates Om~ and Ema x varlaUon with 0) is discussed in detail Finally we discuss an passing o M. and the electrosorptlon valency an this context.

Adsorption isotherms for neutral organic compounds - A hierarchy in modelling: Part V. Models for the inner layer potential difference in the presence of dipolar adsorption

The relations for the inner layer potential &fference (E) in the presence of adsorbed orgamc molecules are derived for three hterarchlcal models, m terms of molecular constants like permanent &pole moments, polarlzablhtles, etc It is shown how the experimentally observed patterns of the E vs 0 plots (hnear m all ranges of $\sigma^M$, non-linear in one or both regions of o M, etc ) can be understood in a serm-quantltatlve manner from the simplest model in our hierarchy, viz the two-state site panty version Two-state multi-site and three-state (sxte panty) models are also analysed and the slope (3E/80),,M tabulated for these also The results for the Esm-Markov effect are denved for all the models and compared with the earlier result of Parsons. A comparison with the GSL phenomenologlcal equation is presented and its molecular basis, as well as the hmltatlons, is analysed. In partxcular, two-state multa-slte and three-state (site panty) models yield E-o M relations that are more general than the "umfied" GSL equation The posslblhty of vaewlng the compact layer as a "composite medium" with an "effective dlelectnc constant" and obtaimng novel phenomenological descnptions IS also indicated.

Catalytic transformation of aliphatic alcohols to corresponding esters in O2 under neutral conditions using visible-light irradiation

Selective oxidation of aliphatic alcohols under mild and base-free conditions is a challenging process for organic synthesis. Herein, we report a one-pot process for the direct oxidative esterification of aliphatic alcohols that is significantly enhanced by visible-light irradiation at ambient temperatures. The new methodology uses heterogenerous photocatalysts of gold–palladium alloy nanoparticles on a phosphate-modified hydrotalcite support and molecular oxygen as a benign oxidant. The alloy photocatalysts can absorb incident light, and the light-excited metal electrons on the surface of metal nanoparticles can activate the adsorbed reactant molecules. Tuning the light intensity and wavelength of the irradiation can remarkably change the reaction activity. Shorter wavelength light (<550 nm) drives the reaction more efficiently than light of longer wavelength (e.g., 620 nm), especially at low temperatures. The phosphate-exchanged hydrotalcite support provides sufficient basicity (and buffer) for the catalytic reactions; thus, the addition of base is not required. The photocatalysts are efficient and readily recyclable. The findings reveal the first example of using “green” oxidants and light energy to drive direct oxidative esterification of aliphatic alcohols under base-free, mild conditions.

Estimation of cosmological parameters from neutral hydrogen observations of the post-reionization epoch

The emission from neutral hydrogen (HI) clouds in the post-reionization era (z <= 6), too faint to be individually detected, is present as a diffuse background in all low frequency radio observations below 1420MHz. The angular and frequency fluctuations of this radiation (similar to 1 mK) are an important future probe of the large-scale structures in the Universe. We show that such observations are a very effective probe of the background cosmological model and the perturbed Universe. In our study we focus on the possibility of determining the redshift-space distortion parameter beta, coordinate distance r(nu), and its derivative with redshift r(nu)('). Using reasonable estimates for the observational uncertainties and configurations representative of the ongoing and upcoming radio interferometers, we predict parameter estimation at a precision comparable with supernova Ia observations and galaxy redshift surveys, across a wide range in redshift that is only partially accessed by other probes. Future HI observations of the post-reionization era present a new technique, complementing several existing ones, to probe the expansion history and to elucidate the nature of the dark energy.

A comparison of a blocking ELISA and a haemagglutination inhibition assay for the detection of antibodies to Avibacterium (Haemophilus) paragallinarum in sera from artificially infected chickens

The ability of blocking ELISAs and haemagglutination-inhibition (HI) tests to detect antibodies in sera from chickens challenged with either Avibacterium (Haemophilus) paragallinarum isolate Hp8 (serovar A) or H668 (serovar C) was compared. Serum samples were examined weekly over the 9 weeks following infection. The results showed that the positive rate of serovar A specific antibody in the B-ELISA remained at 100% from the second week to the ninth week. In chickens given the serovar C challenge, the highest positive rate of serovar C specific antibody in the B-ELISA appeared at the seventh week (60% positive) and was then followed by a rapid decrease. The B-ELISA gave significantly more positives at weeks 2, 3, 7, 8 and 9 post-infection for serovar A and at week 7 post-infection for serovar C. In qualitative terms, for both serovar A and serovar C infections, the HI tests gave a lower percentage of positive sera at all time points except at 9 weeks post-infection with serovar C. The highest positive rate for serovar A HI antibodies was 70% of sera at the fourth and fifth weeks post-infection. The highest rate of serovar C HI antibodies was 20% at the fifth and sixth weeks post-infection. The results have provided further evidence of the suitability of the serovar A and C B-ELISAs for the diagnosis of infectious coryza.

A Front end Switched Rectifier DC Source for Neutral Point Balancing of A NPC Three-Level Inverter for The Full Modulation Range

A switched DC voltage three level NPC is proposed in this paper to eliminate capacitor balancing problems in conventional three-level Neutral Point Clamped (NPC) inverter. The proposed configuration requires only one DC link with a voltage V-dc/2, where V-dc is the DC link voltage in a onventional NPC inverter. To get rated DC link voltage (V-dc), the voltage source is alternately onnected in parallel to one of the two series capacitors using two switches and two diodes with device voltage rating of V-dc/2. The frequency at which the voltage source is switched is independent and will not affect the operation of NPC inverter. The switched voltage source in this configuration balances the capacitors automatically. The proposed configuration can also be used as a conventional two level inverter in lower modulation range, thereby increases the reliability of the drive system. A space vector based PWM scheme is used to verify this proposed topology.

Alfven surface waves along a cylindrical plasma column surrounded by neutral gas

The dispersion characteristics of Alfven surface waves along a cylindrical plasma column insulated by a neutral gas are discussed. There is no qualitative change in the characteristic curves below the critical magnetic field, given by vA approximately=s, as compared to the propagation of surface waves along the plasma-plasma interface. For magnetic fields above this critical value, there exists a cut-off wave number kc, which depends upon the azimuthal wave number, the radius of the cylinder, the strength of the magnetic field above the critical value and the gas pressure, such that surface waves do not exist for k

Inhibition of mitochondrial oxidative phosphorylation by adriamycin

The antitumour antibiotic, adriamycin, inhibited oxidative phosphorylation in freshly prepared mitochondria from the heart, liver and kidney of the rat. It abolished respiratory control and stimulated ATPase activity. Sccinate oxidation by heart mitochondria was extremely sensitive to the drug when hexokinase was present in the reaction medium. The sensitive site has been identified to lie in the region between the succinate dehydrogenase flavoprotein and ubiquinone of the respiratory chain.

A hexokinase effect in the inhibition of oxidative phosphorylation in heart muscle mitochondria by Adriamycin

The inhibitory action of the anticancer antibiotic, Adriamycin, on succinate-dependent oxidative phosphorylation in heart mitochondria was markedly potentiated by the presence of hexokinase in the reaction medium. This 'hexokinase effect' was not observed in the oxidation of NAD+-linked substrates, or when liver or kidney mitochondria were used in place of heart mitochondria. These results offer a biochemical explanation for the extreme cardiac toxicity of the drug.

The role of catechol-O-methyltransferase (COMT) and the effects of COMT inhibition in brain and in cardiovascular and renal pathophysiology

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine (DA), noradrenaline (NA) and adrenaline, which are vital neurotransmitters and hormones that play important roles in the regulation of physiological processes. COMT enzyme has a functional Val158Met polymorphism in humans, which affects the subjects COMT activity. Increasing evidence suggests that this functional polymorphism may play a role in the etiology of various diseases from schizophrenia to cancers. The aim of this project was to provide novel biochemical information on the physiological and especially pathophysiological roles of COMT enzyme as well as the effects of COMT inhibition in the brain and in the cardiovascular and renal system. To assess the roles of COMT and COMT inhibition in pathophysiology, we used four different study designs. The possible beneficial effects of COMT inhibition were studied in double-transgenic rats (dTGRs) harbouring human angiotensinogen and renin genes. Due to angiotensin II (Ang II) overexpression, these animals exhibit severe hypetension, cardiovascular and renal end-organ damage and mortality of approximately 25-40% at the age of 7-weeks. The dTGRs and their Sprague-Dawley controls tissue samples were assessed with light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and high-pressure liquid chromatography (HPLC) to evaluate the tissue damages and the possible protective effects pharmacological intervention with COMT inhibitors. In a second study, the consequence of genetic and pharmacological COMT blockade in blood pressure regulation during normal and high-sodium was elucidated using COMT-deficient mice. The blood pressure and the heart rate were measured using direct radiotelemetric blood pressure surveillance. In a third study, the effects of acute and subchronic COMT inhibition during combined levodopa (L-DOPA) + dopa decarboxylase inhibitor treatment in homocysteine formation was evaluated. Finally, we assessed the COMT enzyme expression, activity and cellular localization in the CNS during inflammation-induced neurodegeneration using Western blotting, HPLC and various enzymatic assays. The effects of pharmacological COMT inhibition on neurodegeneration were also studied. The COMT inhibitor entacapone protected against the Ang II-induced perivascular inflammation, renal damage and cardiovascular mortality in dTGRs. COMT inhibitors reduced the albuminuria by 85% and prevented the cardiovascular mortality completely. Entacapone treatment was shown to ameliorate oxidative stress and inflammation. Furthermore, we established that the genetic and pharmacological COMT enzyme blockade protects against the blood pressure-elevating effects of high sodium intake in mice. These effects were mediated via enhanced renal dopaminergic tone and suggest an important role of COMT enzyme, especially in salt-sensitive hypertension. Entacapone also ameliorated the L-DOPA-induced hyperhomocysteinemia in rats. This is important, since decreased homocysteine levels may decrease the risk of cardiovascular diseases in Parkinson´s disease (PD) patients using L-DOPA. The Lipopolysaccharide (LPS)-induced inflammation and subsequent delayed dopaminergic neurodegeneration were accompanied by up-regulation of COMT expression and activity in microglial cells as well as in perivascular cells. Interestingly, similar perivascular up-regulation of COMT expression in inflamed renal tissue was previously noted in dTGRs. These results suggest that inflammation reactions may up-regulate COMT expression. Furthermore, this increased glial and perivascular COMT activity in the central nervous system (CNS) may decrease the bioavailability of L-DOPA and be related to the motor fluctuation noted during L-DOPA therapy in PD patients.

Trafficking and ethanol-induced inhibition of AMPA receptors

AMPA receptors are an important class of ionotropic glutamate receptors which participate in fast excitatory synaptic transmission in most brain areas. They have a pivotal role in adjustment of cell membrane excitability as their cell membrane expression levels is altered in brain physiology such as in learning and memory formation. AMPA receptor function and trafficking is regulated by several proteins, such as transmembrane AMPA receptor regulatory proteins (TARPs). NMDA-type glutamate receptors are important target molecules of ethanol. The role of AMPA receptors in the actions of ethanol has not been clarified as thoroughly. Furthermore, the regulation of AMPA receptor synthesis and their possible adaptation in neurons with altered inhibitory mechanisms are poorly understood. In this thesis work AMPA receptor pharmacology, trafficking and synaptic localization was studied using patch-clamp electrophysiology. Both native and recombinant AMPA receptors were studied. Hippocampal slices from transgenic Thy1alfa6 mice with altered inhibition were used to study adaptation of AMPA receptors. Ethanol was found to inhibit AMPA receptor function by increasing desensitization of the receptor, as the steady-state current was inhibited more than the peak current. Ethanol inhibition was reduced when cyclothiazide was used to block desensitization and when non-desensitizing mutant receptors were studied. Ethanol also increased the rate of desensitization, which was increased further by the coexpression of TARP-proteins. We found that the agonist binding capability is important for trafficking AMPA receptors from endoplasmic reticulum to the cell membrane. TARP rescues the surface expression of non-binding AMPA receptor mutants in HEK293 cells, but not in native neurons. Studies with Thy1alfa6 mice revealed that decreased inhibition decrease AMPA receptor mediated excitation keeping the neurotransmission in balance. Thy1alfa6 mice also had lower sensitivity to electroshock convulsions, presumably due to the decreased AMPA receptor function. The results suggest that during alcohol intoxication ethanol may inhibit AMPA receptors by increasing the rate and the extent of desensitization. TARPs appear to enhance ethanol inhibition. TARPs also participate in trafficking of AMPA receptors upon their synthesis in the cell. AMPA receptors mediate also long-term adaptation to altered neuronal excitability, which adds to their well-known role in synaptic plasticity.

Inhibition of H2O2 generation in rat liver mitochondria by radical quenchers and phenolic compounds

Generation of H2O2 by rat liver mitochondria with choline, glycerol 1-phosphate and proline as substrates has been shown by using high-concentration phosphate buffer. Rates obtained under these conditions were higher and more consistent as compared with the earlier reports with high-concentration mannitol/sucrose/Tris buffer. Sulphate ions could replace phosphate indicating a requirement for a high concentration of oxygen-containing anions. H2O2 generation was dependent on the presence of native mitochondria and substrate. Maximal rates with various substrates were found to be the same as with succinate. Values of Km and Vmax for H2O2 generation were considerably less than those obtained for respective dehydrogenase activities, measured by dye reduction. Scavengers of O2-. and OH. inhibited generation of H2O2. ATP, ADP, thyronine derivatives and a number of phenolic compounds also showed very potent inhibitory effects of H2O2 generation, whereas phenyl compound had no effect. Phenolic compounds did not have any effect on mitochondrial superoxide dismutase and choline dehydrogenase activities as well as on O2-. generation by the xanthine-xanthine oxidase system. Inhibition by phenolic compounds may have potential for regulation of the intracellular concentration of H2O2, that is not considered to have a "second messenger' function.

A conformational approach to the study of the dynamics of enzyme inhibition: studies on thermolysin

The preferred conformations of β-phenylpropionyl-Image -phenylalanine (β-PPP) and N-carbobenzoxy-L-phenylalanine (Cbz-Phe), two inhibitors of thermolysin, have been determined by computing potential energy using empirial potential energy functions. Of the 15 to 20 conformations that are favoured for each of these inhibitors only a few have the right conformation to reach the active site of the enzyme. The conformer of β-PPP that initiates binding with the enzyme is different from the bound one, while for Cbz-Phe the bound and initiating conformers are quite similar. Thus, β-PPP favours the ‘induced fit’ model while Cbz-Phe follows the ‘lock and key’ model of binding. The inhibitors differ in their alignment at the active site.