Mirroring Enzymes: The Role of H-Bonding In HQuin-BAM Catalyzed Asymmetric Aza-Henry Reactions: A DFT Study into the Reactivity, Mechanism, and Origins of Selectivity

The exact mechanistic understanding of various organocatalytic systems in asymmetric reactions such as Henry and aza-Henry transformations is important for developing and designing new synthetic organocatalysts. The focus of this dissertation will be on the use of density functional theory (DFT) for studying the asymmetric aza-Henry reaction. The first part of the thesis is a detailed mechanistic investigation of a poorly understood chiral bis(amidine) (BAM) Brønsted acid catalyzed aza-Henry reaction between nitromethane and N-Boc phenylaldimine. The catalyst, in addition to acting as a Brønsted base, serves to simultaneously activate both the electrophile and the nucleophile through dual H-bonding during C-C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the H-bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive charge-assisted H-bond, which in turn governed the relative orientation of substrate binding. Attracted by this well-defined mechanistic investigation, the other important aspect of my PhD research addressed a detailed theoretical analysis accounting for the observed selectivity in diastereoselective versions of this reaction. A detailed inspection of the stereodetermining C-C bond forming transition states for monoalkylated nitronate addition to a range of electronically different aldimines, revealed that the origins of stereoselectivity were controlled by a delicate balance of different factors such as steric, orbital interactions, and the extent of distortion in the catalyst and substrates. The structural analysis of different substituted transition states established an interesting dependency on matching the shape and size of the catalyst (host molecule) and substrates (guest molecules) upon binding, both being key factors governing selectivity, in essence, offering an analogy to positive cooperative binding effect of catalytic enzymes and substrates in Nature. In addition, both intra-molecular (intra-host) and inter-molecular (host-guest, guest-guest) stabilizing interactions play a key role to the high π-facial selectivity. The application of dispersion-corrected functionals (i.e., ωB97X-D and B3LYP-D3) was essential for accurately modeling these stabilizing interactions, indicating the importance of dispersion effects in enantioselectivity. As a brief prelude to more extensive future studies, the influence of a triflate counterion on both reactivity and selectivity in this reaction was also addressed.

Synthèse d’un inhibiteur de la rénine, l’aliskiren et développement de méthodes catalytiques d’alkylation asymétrique

Une nouvelle approche pour la synthèse de l’aliskiren, un puissant inhibiteur de la rénine pour le traitement de l’hypertension chez l’homme, a été développée. De cette approche, des étapes clés tels qu’une allylation avec un des catalyseurs de MacMillan, une cyclisation par métathèse (RCM) pour la préparation d’une lactone à neuf membres et une séquence de réactions d’aziridination diastéréosélective/réarrangement de cycle par une catalyse acide donnant un produit aminohydroxylé ont permis de compléter la synthèse de l’aliskiren en 11 étapes. Durant l’élaboration de la séquence de réactions pour la préparation de l’aliksiren, il a été noté que la lactone à neuf membres avait une facilité à se réarranger via des intermédiaires quinonoïdaux et les produits issus de cette tendance ont été analysés. De plus, une étude sur la réaction de RCM, donnant la lactone à neuf membres, a montré une dépendance envers la nature diastéréomérique du substrat de départ. Une méthodologie d’alpha-allylation asymétrique de cétones catalysée au palladium, tirant avantage d’un ligand chiral PHOX, a été explorée et utilisée en vue de la synthèse de l’aliskiren. De cette méthode, une étude pour la synthèse de produits alpha-allylcétones acycliques a été démontrée et un effet d’additif sur la sélectivité et la vitesse de réaction a été découvert. De plus, la production d’un intermédiaire avancé d’un produit d’intérêts a été accomplie et la nature de la contribution de l’additif a été investiguée. Les produits obtenus depuis la méthodologie d’allylation catalysée au palladium et la formation d’intermédiaire cationique des certains dérivés de la synthèse de l’aliskiren ont inspirés une nouvelle approche faisant appel à des techniques d’alkylation en catalyse acide pour la formation de produits diaryliques. Il a été trouvé que le catalyseur de chlorure d’or(III) et de triflate de bismuth(III) étaient particulièrement efficaces, démontrant une différence de cinétique pour la réactivité d’un mélange diastéréoisomériques d’alcools alpha-substitués de départ.

Liquid phase benzylation of o-xylene over pillared clays

Iron, aluminium and mixed iron aluminium pillared clays have been prepared by partial hydrolysis method and doped with IO% Mo, V and Cr. The samples have been characterised by XRD, FTIR and surface area and pore Volume measurements. The surface acid site distribution has been determined by temperature programmed desorption of ammonia. Vanadia incorporated systems show maximum acidity. Benzylation of o-xylene has been done as probe reaction to test catalytic activity. Benzyl chloride is a superior benzylating agent compared to benzyl alcohol in activity and selectivity. Cent percent selectivity towards monobenzylated product is obtained in all the cases. Fe pillared systems exhibit maximum activity. The catalytic activities of the systems can be correlated with the amount of strong add sites. The effects of various reaction variables on the reaction have been studied. Presence of moisture has a diminishing effect on the reaction rate.

A Study of Single Stage Semi‐Dry Anaerobic Digestion of Organic Fraction of Municipal Solid Waste

Solid waste generation is a natural consequence of human activity and is increasing along with population growth, urbanization and industrialization. Improper disposal of the huge amount of solid waste seriously affects the environment and contributes to climate change by the release of greenhouse gases. Practicing anaerobic digestion (AD) for the organic fraction of municipal solid waste (OFMSW) can reduce emissions to environment and thereby alleviate the environmental problems together with production of biogas, an energy source, and digestate, a soil amendment. The amenability of substrate for biogasification varies from substrate to substrate and different environmental and operating conditions such as pH, temperature, type and quality of substrate, mixing, retention time etc. Therefore, the purpose of this research work is to develop feasible semi-dry anaerobic digestion process for the treatment of OFMSW from Kerala, India for potential energy recovery and sustainable waste management. This study was carried out in three phases in order to reach the research purpose. In the first phase, batch study of anaerobic digestion of OFMSW was carried out for 100 days at 32°C (mesophilic digestion) for varying substrate concentrations. The aim of this study was to obtain the optimal conditions for biogas production using response surface methodology (RSM). The parameters studied were initial pH, substrate concentration and total organic carbon (TOC). The experimental results showed that the linear model terms of initial pH and substrate concentration and the quadratic model terms of the substrate concentration and TOC had significant individual effect (p < 0.05) on biogas yield. However, there was no interactive effect between these variables (p > 0.05). The optimum conditions for maximizing the biogas yield were a substrate concentration of 99 g/l, an initial pH of 6.5 and TOC of 20.32 g/l. AD of OFMSW with optimized substrate concentration of 99 g/l [Total Solid (TS)-10.5%] is a semi-dry digestion system .Under the optimized condition, the maximum biogas yield was 53.4 L/kg VS (volatile solid).. In the second phase, semi-dry anaerobic digestion of organic solid wastes was conducted for 45 days in a lab-scale batch experiment for substrate concentration of 100 g/l (TS-11.2%) for investigating the start-up performances under thermophilic condition (50°C). The performance of the reactor was evaluated by measuring the daily biogas production and calculating the degradation of total solids and the total volatile solids. The biogas yield at the end of the digestion was 52.9 L/kg VS for the substrate concentration of 100 g/l. About 66.7% of volatile solid degradation was obtained during the digestion. A first order model based on the availability of substrate as the limiting factor was used to perform the kinetic studies of batch anaerobic digestion system. The value of reaction rate constant, k, obtained was 0.0249 day-1. A laboratory bench scale reactor with a capacity of 36.8 litres was designed and fabricated to carry out the continuous anaerobic digestion of OFMSW in the third phase. The purpose of this study was to evaluate the performance of the digester at total solid concentration of 12% (semi-dry) under mesophlic condition (32°C). The digester was operated with different organic loading rates (OLRs) and constant retention time. The performance of the reactor was evaluated using parameters such as pH, volatile fatty acid (VFA), alkalinity, chemical oxygen demand (COD), TOC and ammonia-N as well as biogas yield. During the reactor’s start-up period, the process is stable and there is no inhibition occurred and the average biogas production was 14.7 L/day. The reactor was fed in continuous mode with different OLRs (3.1,4.2 and 5.65 kg VS/m3/d) at constant retention time of 30 days. The highest volatile solid degradation of 65.9%, with specific biogas production of 368 L/kg VS fed was achieved with OLR of 3.1 kg VS/m3/d. Modelling and simulation of anaerobic digestion of OFMSW in continuous operation is done using adapted Anaerobic Digestion Model No 1 (ADM1).The proposed model, which has 34 dynamic state variables, considers both biochemical and physicochemical processes and contains several inhibition factors including three gas components. The number of processes considered is 28. The model is implemented in Matlab® version 7.11.0.584(R2010b). The model based on adapted ADM1 was tested to simulate the behaviour of a bioreactor for the mesophilic anaerobic digestion of OFMSW at OLR of 3.1 kg VS/m3/d. ADM1 showed acceptable simulating results.

Effect of environmental conditions on the N uptake route of soil microorganisms and adaption of a method to determine amino acid oxidase in soil

Soil microorganisms have evolved two possible mechanisms for their uptake of organic N: the direct route and the mobilization-immobilization-turnover (MIT) route. In the direct route, simple organic molecules are taken up via various mechanisms directly into the cell. In the MIT route, the deamination occurs outside the cell and all N is mineralized to NH4+ before assimilation. A better understanding of the mechanisms controlling the different uptake routes of soil microorganisms under different environmental conditions is crucial for understanding mineralization processes of organic material in soil. For the first experiment we incubated soil samples from the long term trial in Bad Lauchstädt with corn residues with different C to N ratios and inorganic N for 21 days at 20 °C. Under the assumption that all added amino acids were taken up or mineralized, the direct uptake route was more important in soil amended with corn residues with a wide C to N ratio. After 21 days of incubation the direct uptake of added amino acids increased in the order addition of corn residue with a: “C to N ratio of 40 & (NH4)2SO4 and no addition (control)” (69% and 68%, respectively) < “C to N ratio of 20” (73%) < “C to N ratio of 40” (95%). In all treatments the proportion of the added amino acids that were mineralized increased with time, indicating that the MIT route became more important over time. To investigate the effects of soil depth on the N uptake route of soil microorganisms (experiment II), soil samples in two soil depths (0-5 cm; 30-40 cm) were incubated with corn residues with different C to N ratios and inorganic N for 21 days at 20 °C and 60% (WHC). The addition of corn residue resulted in a marked increase of protease activity in both depths due to the induction from the added substrate. Addition of corn residue with a wide C to N ratio resulted in a significantly greater part of the direct uptake (97% and 94%) than without the addition of residues (85% and 80%) or addition of residue with a small C to N ratio (90% and 84%) or inorganic N (91% and 79% in the surface soil and subsoil, respectively), suggesting that under conditions of sufficient mineralizable N (C to N ratio of 20) or increased concentrations of NH4+, the enzyme system involved in the direct uptake is slightly repressed. Substrate additions resulted in an initially significantly higher increase of the direct uptake in the surface soil than in the subsoil. As a large proportion of the organic N input into soil is in form of proteinaceous material, the deamination of amino acids is a key reaction of the MIT route. Therefore the enzyme amino acid oxidase contribute to the extracellular N mineralization in soil. The objective of experiment III was to adapt a method to determine amino acid oxidase in soil. The detection via synthetic fluorescent Lucifer Yellow derivatives of the amino acid lysine is possible in soil. However, it was not possible to find the substrate concentration at which the reaction rate is independent of substrate concentration and therefore we were not able to develop a valid soil enzyme assay.

Oxidation of silicon: further tests for the interfacial silicon emission model

The classical description of Si oxidation given by Deal and Grove has well-known limitations for thin oxides (below 200 Ã). Among the large number of alternative models published so far, the interfacial emission model has shown the greatest ability to fit the experimental oxidation curves. It relies on the assumption that during oxidation Si interstitials are emitted to the oxide to release strain and that the accumulation of these interstitials near the interface reduces the reaction rate there. The resulting set of differential equations makes it possible to model diverse oxidation experiments. In this paper, we have compared its predictions with two sets of experiments: (1) the pressure dependence for subatmospheric oxygen pressure and (2) the enhancement of the oxidation rate after annealing in inert atmosphere. The result is not satisfactory and raises serious doubts about the model’s correctness

A review of dissolved oxygen modelling techniques for lowland rivers

This review introduces the methods used to simulate the processes affecting dissolved oxygen (DO) in lowland rivers. The important processes are described and this provides a modelling framework to describe those processes in the context of a mass-balance model. The process equations that are introduced all require (reaction) rate parameters and a variety of common procedures for identifying those parameters are reviewed. This is important because there is a wide range of estimation techniques for many of the parameters. These different techniques elicit different estimates of the parameter value and so there is the potential for a significant uncertainty in the model's inputs and therefore in the output too. Finally, the data requirements for modelling DO in lowland rivers are summarised on the basis of modelling the processes described in this review using a mass-balance model. This is reviewed with regard to what data are available and from where they might be obtained. (C) 2003 Elsevier Science B.V. All rights reserved.

Electrochemical and sonoelectrochemical monitoring of indigo reduction by glucose

The reduction of indigo (dispersed in water) to leuco-indigo (dissolved in water) is an important industrial process and investigated here for the case of glucose as an environmentally benign reducing agent. In order to quantitatively follow the formation of leuco-indigo two approaches based on (i) rotating disk voltammetry and (ii) sonovoltammetry are developed. Leuco-indigo, once formed in alkaline solution, is readily monitored at a glassy carbon electrode in the mass transport limit employing hydrodynamic voltammetry. The presence of power ultrasound further improves the leuco-indigo determination due to additional agitation and homogenization effects. While inactive at room temperature, glucose readily reduces indigo in alkaline media at 65 degrees C. In the presence of excess glucose, a surface dissolution kinetics limited process is proposed following the rate law d eta(leuco-indigo)/dt = k x c(OH-) x S-indigo where eta(leuco-indigo) is the amount of leuco-indigo formed, k = 4.1 x 10(-9) m s(-1) (at 65 degrees C, assuming spherical particles of I gm diameter) is the heterogeneous dissolution rate constant,c(OH-) is the concentration of hydroxide, and Sindigo is the reactive surface area. The activation energy for this process in aqueous 0.2 M NaOH is E-A = 64 U mol(-1) consistent with a considerable temperature effects. The redox mediator 1,8-dihydroxyanthraquinone is shown to significantly enhance the reaction rate by catalysing the electron transfer between glucose and solid indigo particles. (c) 2006 Elsevier Ltd. All fights reserved.

In situ observation of lithium hydride hydrolysis by DRIFT spectroscopy

Polycrystalline LiH was studied in situ using diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy to investigate the effect water vapour has on the rate of production of the corrosion products, particularly LiOH. The reaction rate of the formation of surface LiOH was monitored by measurement of the hydroxyl (OH) band at 3676 cm(-1). The initial hydrolysis rate of LiH exposed to water vapour at 50% relative humidity was found to be almost two times faster than LiH exposed to water vapour at 2% relative humidity. The hydrolysis rate was shown to be initially very rapid followed by a much slower, almost linear rate. The change in hydrolysis rate was attributed to the formation of a coherent layer of LiOH on the LiH surface. Exposure to lower levels of water vapour appeared to result in the formation of a more coherent corrosion product, resulting in effective passivation of the surface to further attack from water. Crown Copyright (c) 2007 Published by Elsevier B.V. All rights reserved.

Synthesis of isomaltooligosaccharides and oligodextrans by the combined use of dextransucrase and dextranase

Batch syntheses of isomaltooligosaccharides (IMO) from sucrose, using the enzymes dextransucrase and dextranase were performed with the aim of understanding the reaction mechanism and the parameters which affect product characteristics and molecular size. Both activities described for dextransucrase (dextran formation and acceptor reaction) achieved synthesis whilst the hydrolytic activity of dextranase regulated the product molecular size and acceptor availability. Depending on the reaction conditions, the product oligosaccharide mixtures contained mainly sugars (up to 36%) with degrees of polymerization (DP) varying between 10 and 60 together with lower concentrations of both lower and higher molecular weight sugars. Alterations in substrate and dextranase concentrations (50-400 mg ml(-1) and 2.5-46 U ml(-1), respectively) affected the molecular weight of IMO, the reaction rate and the formation of leucrose. This permitted manipulation of the product characteristics. It was found that higher substrate and dextranase concentrations gave rise to products with lower molecular sizes and a dextransucrase:dextranase ratio of 1: 1 or 1:2 appeared to produce a polymer with a molecular weight which is desirable for prebiotic use. (C) 2004 Elsevier Inc. All rights reserved.

Surface science studies of strong metal-oxide interactions on model catalysts

The strong metal support interaction (SMSI) was first described in 1978 by Tauster [1-4]. The effect was observed as a severely negative effect on CO and H2 uptake on the catalyst after high temperature calcination under reducing conditions (heating above ~ 700 K) [1,2]. It also had a negative effect on the reaction rate for reactions, such as alkane hydrogenolysis [5,6]. It appeared that the effect occurred for catalysts comprised of reducible supports which were treated at elevated temperature in reducing conditions [2-4]. A classic support which has manifested this behaviour in many studies is TiO2. Over the years following the first discovery of SMSI it has been recognised that the effect is not always negative – for instance for the CO-H2 reaction for which it appears to have a positive effect [5,6]. Further it was noted that hydrogen reduction was not necessary to observe the effect of CO adsorption suppression, it also occurs by vacuum treatment [7], though it should be noted that vacuum treatment at elevated temperature is, in effect, a reducing environment.

Coupling aerosol surface and bulk chemistry with a kinetic double layer model (K2-SUB): oxidation of oleic acid by ozone

We present a kinetic double layer model coupling aerosol surface and bulk chemistry (K2-SUB) based on the PRA framework of gas-particle interactions (Poschl-Rudich-Ammann, 2007). K2-SUB is applied to a popular model system of atmospheric heterogeneous chemistry: the interaction of ozone with oleic acid. We show that our modelling approach allows de-convoluting surface and bulk processes, which has been a controversial topic and remains an important challenge for the understanding and description of atmospheric aerosol transformation. In particular, we demonstrate how a detailed treatment of adsorption and reaction at the surface can be coupled to a description of bulk reaction and transport that is consistent with traditional resistor model formulations. From literature data we have derived a consistent set of kinetic parameters that characterise mass transport and chemical reaction of ozone at the surface and in the bulk of oleic acid droplets. Due to the wide range of rate coefficients reported from different experimental studies, the exact proportions between surface and bulk reaction rates remain uncertain. Nevertheless, the model results suggest an important role of chemical reaction in the bulk and an approximate upper limit of similar to 10(-11) cm(2) s(-1) for the surface reaction rate coefficient. Sensitivity studies show that the surface accommodation coefficient of the gas-phase reactant has a strong non-linear influence on both surface and bulk chemical reactions. We suggest that K2-SUB may be used to design, interpret and analyse future experiments for better discrimination between surface and bulk processes in the oleic acid-ozone system as well as in other heterogeneous reaction systems of atmospheric relevance.

Properties of thick evaporated layers of PbTe

The changes in the optical transparency of PbTe monolayers induced by post-evaporation heat treatment are described. The monolayers are typically a few microns in thickness and heat treatment reduces the carrier density from about 1018 (n-type) per cm3 to 1017 per cm3 : the source material is 1019 (ptype) per cm3. The process seems to involve the diffusion of O2 at a reaction rate equivalent to an energy of 0.83 eV.

Determination of the degradation kinetics of anthocyanins in a model juice system using isothermal and non-isothermal methods

The effect of temperature on the degradation of blackcurrant anthocyanins in a model juice system was determined over a temperature range of 4–140 °C. The thermal degradation of anthocyanins followed pseudo first-order kinetics. From 4–100 °C an isothermal method was used to determine the kinetic parameters. In order to mimic the temperature profile in retort systems, a non-isothermal method was applied to determine the kinetic parameters in the model juice over the temperature range 110–140 °C. The results from both isothermal and non-isothermal methods fit well together, indicating that the non-isothermal procedure is a reliable mathematical method to determine the kinetics of anthocyanin degradation. The reaction rate constant (k) increased from 0.16 (±0.01) × 10−3 to 9.954 (±0.004) h−1 at 4 and 140 °C, respectively. The temperature dependence of the rate of anthocyanin degradation was modelled by an extension of the Arrhenius equation, which showed a linear increase in the activation energy with temperature.

Kinetics analysis and automated online screening of aminocarbonylation of aryl halides in flow

Temperature, pressure, gas stoichiometry, and residence time were varied to control the yield and product distribution of the palladium-catalyzed aminocarbonylation of aromatic bromides in both a silicon microreactor and a packed-bed tubular reactor. Automation of the system set points and product sampling enabled facile and repeatable reaction analysis with minimal operator supervision. It was observed that the reaction was divided into two temperature regimes. An automated system was used to screen steady-state conditions for offline analysis by gas chromatography to fit a reaction rate model. Additionally, a transient temperature ramp method utilizing online infrared analysis was used, leading to more rapid determination of the reaction activation energy of the lower temperature regimes. The entire reaction spanning both regimes was modeled in good agreement with the experimental data.