Studies in three phase gas-liquid-solid fluidised systems

The work is a logical continuation of research started at Aston some years ago when studies were conducted on fermentations in bubble columns. The present work highlights typical design and operating problems that could arise in such systems as waste water, chemical, biochemical and petroleum operations involving three-phase, gas-liquid-solid fluidisation; such systems are in increasing use. It is believed that this is one of few studies concerned with `true' three-phase, gas-liquid-solid fluidised systems, and that this work will contribute significantly to closing some of the gaps in knowledge in this area. The research work was mainly experimentally based and involved studies of the hydrodynamic parameters, phase holdups (gas and solid), particle mixing and segregation, and phase flow dynamics (flow regime and circulation patterns). The studies have focused particularly on the solid behaviour and the influence of properties of solids present on the above parameters in three-phase, gas-liquid-solid fluidised systems containing single particle components and those containing binary and ternary mixtures of particles. All particles were near spherical in shape and two particle sizes and total concentration levels were used. Experiments were carried out in two- and three-dimensional bubble columns. Quantitative results are presented in graphical form and are supported by qualitative results from visual studies which are also shown as schematic diagrams and in photographic form. Gas and solid holdup results are compared for air-water containing single, binary and ternary component particle mixtures. It should be noted that the criteria for selection of the materials used are very important if true three-phase fluidisation is to be achieved: this is very evident when comparing the results with those in the literature. The fluid flow and circulation patterns observed were assessed for validation of the generally accepted patterns, and the author believes that the present work provides more accurate insight into the modelling of liquid circulation in bubble columns. The characteristic bubbly flow at low gas velocity in a two-phase system is suppressed in the three-phase system. The degree of mixing within the system is found to be dependent on flow regime, liquid circulation and the ratio of solid phase physical properties. Evidence of strong `trade-off' of properties is shown; the overall solid holdup is believed to be a major parameter influencing the gas holdup structure.

Oxidation studies of a novel barrier polymer system

The thermal oxidation of two model compounds representing the aromatic polyamide, MXD6 (poly m-xylylene adipamide) have been investigated. The model compounds (having different chemical structures, viz, one corresponding to the aromatic part of the chain and the other to the aliphatic part), based on the structure of MXD6 were prepared and reactions with different concentrations of cobalt ions examined with the aim of identifying the role of the different structural components of MXD6 on the mechanism of oxidation. The study showed that cobalt, in the presence of sodium phosphite (which acts as an antioxidant for MXD6 and the model compounds), increases the oxidation of the model compounds. It is believed that the cobalt acts predominantly as a catalyst for the decomposition of hydroperoxides, formed during oxidation of the models in the melt phase, to free radical products and to a lesser extent as a catalyst for the initiation of the oxidation reaction by complex formation with the amide, which is more likely to take place in the solid phase. An oxidation cycle has been proposed consisting of two parts both of which will occur, to some extent under all conditions of oxidation (in the melt and in the solid phase), but their individual predominance must be determined by the prevailing oxygen pressure at the reaction site. The different aspects of this proposed mechanism were examined from extensive model compound studies, and the evidence based on the nature of product formation and the kinetics of these reactions. Main techniques used to compare the rates of oxidation and the study of kinetics included, oxygen absorption, FT-IR, UV and TGA. HPLC was used for product separation and identification.

Factors affecting human reliability in the chemical process industry

This research was concerned with identifying factors which may influence human reliability within chemical process plants - these factors are referred to as Performance Shaping Factors (PSFs). Following a period of familiarization within the industry, a number of case studies were undertaken covering a range of basic influencing factors. Plant records and site `lost time incident reports' were also used as supporting evidence for identifying and classifying PSFs. In parallel to the investigative research, the available literature appertaining to human reliability assessment and PSFs was considered in relation to the chemical process plan environment. As a direct result of this work, a PSF classification structure has been produced with an accompanying detailed listing. Phase two of the research considered the identification of important individual PSFs for specific situations. Based on the experience and data gained during phase one, it emerged that certain generic features of a task influenced PSF relevance. This led to the establishment of a finite set of generic task groups and response types. Similarly, certain PSFs influence some human errors more than others. The result was a set of error type key words, plus the identification and classification of error causes with their underlying error mechanisms. By linking all these aspects together, a comprehensive methodology has been forwarded as the basis of a computerized aid for system designers. To recapitulate, the major results of this research have been: One, the development of a comprehensive PSF listing specifically for the chemical process industries with a classification structure that facilitates future updates; and two, a model of identifying relevant SPFs and their order of priority. Future requirements are the evaluation of the PSF listing and the identification method. The latter must be considered both in terms of `useability' and its success as a design enhancer, in terms of an observable reduction in important human errors.

Chemical and physical methods of enhancing the percutaneous absorption of antimicrobial agents

Contrary to previously held beliefs, it is now known that bacteria exist not only on the surface of the skin but they are also distributed at varying depths beneath the skin surface. Hence, in order to sterilise the skin, antimicrobial agents are required to penetrate across the skin and eliminate the bacteria residing at all depths. Chlorhexidine is an antimicrobial agent with the widest use for skin sterilisation. However, due to its poor permeation rate across the skin, sterilisation of the skin cannot be achieved and, therefore, the remaining bacteria can act as a source of infection during an operation or insertion of catheters. The underlying theme of this study is to enhance the permeation of this antimicrobial agent in the skin by employing chemical (enhancers and supersaturated systems) or physical (iontophoresis) techniques. The hydrochloride salt of chlorhexidine (CHX), a poorly soluble salt, was used throughout this study. The effect of ionisation on in vitro permeation rate across the excised human epidennis was investigated using Franz-type diffusion cells. Saturated solutions of CHX were used as donor and the variable studied was vehicle pH. Permeation rate was increased with increasing vehicle pH. The pH effect was not related to the level of ionisation of the drug. The effect of donor vehicle was also studied using saturated solutions of CHX in 10% and 20% ethanol as the donor solutions. Permeation of CHX was enhanced by increasing the concentration of ethanol which could be due to the higher concentration of CHX in the donor phase and the effect of ethanol itself on the membrane. The interplay between drug diffusion and enhancer pretreatment of the epidennis was studied. Pretreatment of the membrane with 10% Azone/PG demonstrated the highest diffusion rate followed by 10% olcic acid/PG pretreatment compared to other pretreatment regimens (ethanol, dimethyl sulfoxide (DMSO), propylene glycol (PG), sodium dodecyl sulphate (SDS) and dodecyl trimethyl ammonium bromide (DT AB). Differential Scanning Calorimetry (DSC) was also employed to study the mode of action of these enhancers. The potential of supersaturated solutions in enhancing percutaneous absorption of CHX was investigated. Various anti-nucleating polymers were screened in order to establish the most effective agent. Polyvinylpyrrolidone (PVP, K30) was found to be a better candidate than its lower molecular weight counterpart (K25) and hydroxypropyl methyleellulose (HPMC). The permeation studies showed an increase in diffusion rate by increasing the degree of saturation. Iontophoresis is a physical means of transdemal drug delivery enhancement that causes an increased penetration of molecules into or through the skin by the application of an electric field. This technique was employed in conjunction with chemical enhancers to assess the effect on CHX permeation across the human epidermis. An improved transport of CHX, which was pH dependant was observed upon application of the current. Combined use of iontophoresis and chemical enhancers further increased the CHX transport indicating a synergistic effect. Pretreatment of the membrane with 10% Azone/PG demonstrated the greatest effect.

Chemical synthesis of DNA and RNA containing thio-substituted bases and their post-synthetic modifications

Modified oligonucleotides containing sulphur group have been useful tools for studies of carcinogenesis, protein or nucleic acid structures and functions, protein-nucleic acid interactions, and for antisense modulation of gene expression. One successful example has been the synthesis and study of oligodeoxynucleotides containing 6-thio-2'-deoxyguanine. 6-Thio-2-deoxyguanosine was first discovered as metabolic compound of 6- mercaptopurine (6-MP). Later, it was applied as drug to cure leukaemia. During the research of its toxicity, a method was developed to use the sulphur group as a versatile position for post-synthetic modification. The advantage of application of post-synthetic modification lies in its convenience. Synthesis of oligomers with normal sequences has become routine work in most laboratories. However, design and synthesis of a proper phosphoramidite monomer for a new modified nucleoside are always difficult tasks even for a skilful chemist. Thus an alternative method (post-synthetic method) has been invented to overcome the difficulties. This was achieved by incorporation of versatile nucleotides into oligomers which contain a leaving group, that is sufficiently stable to withstand the conditions of synthesis but can be substituted by nucleophiles after synthesis, to produce, a series of oligomers each containing a different modified base. In the current project, a phosphoramidite monomer with 6-thioguanine has been successfully synthesised and incorporated into RNA. A deprotection procedure, which is specific for RNA was designed for oligomers containing 6-thioguanosine. The results were validated by various methods (UV, HPLC, enzymatic digestion). Pioneer work in utilization of the versatile sulphur group for post-synthetic modification was also tested. Post-synthetic modification was also carried out on DNA with 6- deoxythioguanosine. Electrophilic reagents with various functional groups (alphatic, aromatic, fluorescent) and bi-functional groups have been attached with the oligomers.

Nuclear magnetic resonance studies of molecular interactions and structures

This thesis is concerned with the investigation, by nuclear magnetic resonance spectroscopy, of the molecular interactions occurring in mixtures of benzene and cyclohexane to which either chloroform or deutero-chloroform has been added. The effect of the added polar molecule on the liquid structure has been studied using spin-lattice relaxation time, 1H chemical shift, and nuclear Overhauser effect measurements. The main purpose of the work has been to validate a model for molecular interaction involving local ordering of benzene around chloroform. A chemical method for removing dissolved oxygen from samples has been developed to encompass a number of types of sample, including quantitative mixtures, and its supremacy over conventional deoxygenation technique is shown. A set of spectrometer conditions, the use of which produces the minimal variation in peak height in the steady state, is presented. To separate the general diluting effects of deutero-chloroform from its effects due to the production of local order a series of mixtures involving carbon tetrachloride, instead of deutero-chloroform, have been used as non-interacting references. The effect of molecular interaction is shown to be explainable using a solvation model, whilst an approach involving 1:1 complex formation is shown not to account for the observations. It is calculated that each solvation shell, based on deutero-chloroform, contains about twelve molecules of benzene or cyclohexane. The equations produced to account for the T1 variations have been adapted to account for the 1H chemical shift variations in the same system. The shift measurements are shown to substantiate the solvent cage model with a cage capacity of twelve molecules around each chloroform molecule. Nuclear Overhauser effect data have been analysed quantitatively in a manner consistent with the solvation model. The results show that discrete shells only exist when the mole fraction of deutero-chloroform is below about 0.08.

Studies of the effects of molecular encounters on N.M.R. spin-lattice relaxation times

This thesis is concerned with investigations of the effects of molecular encounters on nuclear magnetic resonance spin-lattice relaxation times, with particular reference to mesitylene in mixtures with cyclohexane and TMS. The purpose of the work was to establish the best theoretical description of T1 and assess whether a recently identified mechanism (buffeting), that influences n.m.r. chemical shifts, governs Tl also. A set of experimental conditions are presented that allow reliable measurements of Tl and the N. O. E. for 1H and 13C using both C. W. and F.T. n.m.r. spectroscopy. Literature data for benzene, cyclohexane and chlorobenzene diluted by CC14 and CS2 are used to show that the Hill theory affords the best estimation of their correlation times but appears to be mass dependent. Evaluation of the T1 of the mesitylene protons indicates that a combined Hill-Bloembergen-Purcell-Pound model gives an accurate estimation of T1; subsequently this was shown to be due to cancellation of errors in the calculated intra and intemolecular components. Three experimental methods for the separation of the intra and intermolecular relaxation times are described. The relaxation times of the 13C proton satellite of neat bezene, 1,4 dioxane and mesitylene were measured. Theoretical analyses of the data allow the calculation of Tl intra. Studies of intermolecular NOE's were found to afford a general method of separating observed T1's into their intra and intermolecular components. The aryl 1H and corresponding 13C T1 values and the NOE for the ring carbon of mesitylene in CC14 and C6H12-TMS have been used in combination to determine T1intra and T1inter. The Hill and B.P.P. models are shown to predict similarly inaccurate values for T1linter. A buffeting contribution to T1inter is proposed which when applied to the BPP model and to the Gutowsky-Woessner expression for T1inter gives an inaccuracy of 12% and 6% respectively with respect to theexperimentally based T1inter.

Studies of molecular interactions using physical techniques

The investigations described in this thesis concern the molecular interactions between polar solute molecules and various aromatic compounds in solution. Three different physical methods were employed. Nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine the nature and strength of the interactions and the geometry of the transient complexes formed. Cryoscopic studies were used to provide information on the stoichiometry of the complexes. Dielectric constant studies were conducted in an attempt to confirm and supplement the spectroscopic investigations. The systems studied were those between nitromethane, chloroform, acetonitrile (solutes) and various methyl substituted benzenes. In the n.m.r. work the dependence of the solute chemical shift upon the compositions of the solutions was determined. From this the equilibrium quotients (K) for the formation of each complex and the shift induced in the solute proton by the aromatic in the complex were evaluated. The thermodynamic parameters for the interactions were obtained from the determination of K at several temperatures. The stoichiometries of the complexes obtained from cryoscopic studies were found to agree with those deduced from spectroscopic investigations. For most systems it is suggested that only one type of complex, of 1:1 stiochiometry, predominates except that for the acetonitrile-benzene system a 1:2 complex is formed. Two sets of dielectric studies were conducted, the first to show that the nature of the interaction is dipole-induced dipole and the second to calculate K. The equilibrium quotients obtained from spectroscopic and dielectric studies are compared. Time-averaged geometries of the complexes are proposed. The orientation of solute, with respect to the aromatic for the 1:1 complexes, appears to be the one in which the solute lies symmetrically about the aromatic six-fold axis whereas for the 1:2 complex, a sandwich structure is proposed. It is suggested that the complexes are formed through a dipole-induced dipole interaction and steric factors play some part in the complex formation.

Stability studies on pencillin derivatives

Current analytical assay methods for ampicillin sodium and cloxacillin sodium are discussed and compared, High Performance Liquid Chromatography (H.P.L.C.) being chosen as the most accurate, specific and precise. New H.P.L.C. methods for the analysis of benzathine cloxacillin; benzathine penicillin V; procaine penicillin injection B.P.; benethamine penicillin injection; fortified B.P.C.; benzathine penicillin injection; benzathine penicillin injection, fortified B.P.C.; benzathine penicillin suspnsion; ampicillin syrups and penicillin syrups are described. Mechanical or chemical damage to column packings is often associated with H.P.L.C. analysis. One type, that of channel formation, is investigated. The high linear velocity of solvent and solvent pulsing during the pumping cycle were found to be the cause of this damage. The applicability of nonisotherrnal kinetic experiments to penicillin V preparations, including formulated paediatric syrups, is evaluated. A new type of nonisotherrnal analysis, based on slope estimation and using a 64K Random Access Memory (R.A.M.) microcomputer is described. The name of the program written for this analysis is NONISO. The distribution of active penicillin in granules for reconstitution into ampicillin and penicillin V syrups, and its effect on the stability of the reconstituted products, are investigated. Changing the diluent used to reconstitue the syrups was found to affect the stability of the product. Dissolution and stability of benzathine cloxacillin at pH2, pH6 and pH9 is described, with proposed dissolution mechanisms and kinetic analysis to support these mechanisms. Benzathine and cloxacillin were found to react in solution at pH9, producing an insoluble amide.

Studies of the stability and metabolism of tumour inhibitory tetrazinones

Temozolomide is an imidazotetrazinone with antineoplastic properties. It is structurally related to dacarbazine. Temozolomide was not metabolized in vitro by liver fractions. Chemical decomposition appears to play an important r^ole in its in vitro and in vivo disposition. In contrast, 3-methylbenzotriazinone, a structural analogue, was metabolized by hepatic microsomes to afford benzotriazinone and a hydrophilic metabolite. The cytotoxicity of temozolomide, dacarbazine, 5-[3-(hydroxy-methyl-3-methyl-triazen-1-yl]imidazole-5-carboxamide (HMMTIC) and 3-monomethyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) were investigated in TLX5 murine lymphoma cells. Unlike dacarbazine, which was not toxic, MTIC, HMMTIC and temozolomide were cytotoxic in the absence of microsomes. Decarbazine was only cytotoxic in the presence of microsomes. The formation of MTIC from dacarbazine, HMMTIC and temozolomide was determined by reversed phase high performance liquid chromatography in mixtures incubated under conditions identical to those described before. MTIC was generated chemically from temozolomide and HMMTIC metabolically from dacarbazine. Using [14C]temozolomide, it was found that, in mice, the major route of excretion of the drug is via the kidneys. An acidic metabolite (metabolite I) was found in the urine of mice which had received temozolomide but its identity has not been established. 1H NMR, UV and chemical analyses revealed that Metabolite I possesses an intact NNN linkage and the site of metabolism is at the N3 methyl group. A further acidic metabolite (metabolite II) was found in the urine of patients. Metabolite II was unambiguously identified as the 8-carboxylic acid derivative of temozolomide. In vitro cytotoxicity assay showed that ony metabolite II is cytotoxic but not metabolite I. Pharmacokinetic studies of temozolomide and MTIC in vivo were performed on mice bearing TLX5 tumour. Temozolomide was eliminated from the plasma monophasically with a t1/2 of 0.7hr. MTIC was identified as a product of decomposition. MTIC was eliminated rapidly with a t1/2 of 2min. Though temozolomide shares many biochemical and biological similarities with clinically used dacarbazine, the results obtained in this study show that it differs markedly in its pharmacokinetic properties from dacarbazine, as temozolomide produced relatively sustained plasma levels which were reflected by drug concentrations in the tumour.

Intermediate pyrolysis studies of aquatic biomass and potential applications in the BtVB-process

Aquatic biomass is seen as one of the major feedstocks to overcome difficulties associated with 1st generation biofuels, such as competition with food production, change of land use and further environmental issues. Although, this finding is widely accepted only little work has been carried out to investigate thermo-chemical conversion of algal specimen to produce biofuels, power and heat. This work aims at contributing fundamental knowledge for thermo-chemical processing of aquatic biomass via intermediate pyrolysis. Therefore, it was necessary to install and commission an analytical pyrolysis apparatus which facilitates intermediate pyrolysis process conditions as well as subsequent separation and detection of pyrolysates (Py- GC/MS). In addition, a methodology was established to analyse aquatic biomass under intermediate conditions by Thermo-Gravimetric Analysis (TGA). Several microalgae (e.g. Chlamydomonas reinhardtii, Chlorella vulgaris) and macroalgae specimen (e.g. Fucus vesiculosus) from main algal divisions and various natural habitats (fresh and saline water, temperate and polar climates) were chosen and their thermal degradation under intermediate pyrolysis conditions was studied. In addition, it was of interest to examine the contribution of biochemical constituents of algal biomass onto the chemical compounds contained in pyrolysates. Therefore, lipid and protein fractions were extracted from microalgae biomass and analysed separately. Furthermore, investigations of residual algal materials obtained by extraction of high valuable compounds (e.g. lipids, proteins, enzymes) were included to evaluate their potential for intermediate pyrolysis processing. On basis of these thermal degradation studies, possible applications of algal biomass and from there derived materials in the Bio-thermal Valorisation of Biomass-process (BtVB-process) are presented. It was of interest to evaluate the combination of the production of high valuable products and bioenergy generation derived by micro- and macro algal biomass.

Thermo-chemical behaviour and chemical product formation from Polar seaweeds during intermediate pyrolysis

Fundamental analytical pyrolysis studies of biomass from Polar seaweeds, which exhibit a different biomass composition than terrestrial and micro-algae biomass were performed via thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass-spectrometry (Py-GC/MS). The main reason for this study is the adaptation of these species to very harsh environments making them an interesting source for thermo-chemical processing for bioenergy generation and production of biochemicals via intermediate pyrolysis. Several macroalgal species from the Arctic region Kongsfjorden, Spitsbergen/Norway (Prasiola crispa, Monostroma arcticum, Polysiphonia arctica, Devaleraea ramentacea, Odonthalia dentata, Phycodrys rubens, Sphacelaria plumosa) and from the Antarctic peninsula, Potter Cove King George Island (Gigartina skottsbergii, Plocamium cartilagineum, Myriogramme manginii, Hymencladiopsis crustigena, Kallymenia antarctica) were investigated under intermediate pyrolysis conditions. TGA of the Polar seaweeds revealed three stages of degradation representing dehydration, devolatilization and decomposition of carbonaceous solids. The maximum degradation temperatures Prasiola crispa were observed within the range of 220-320 C and are lower than typically obtained by terrestrial biomass, due to divergent polysaccharide compositions. Biochar residues accounted for 33-46% and ash contents of 27-45% were obtained. Identification of volatile products by Py-GC/MS revealed a complexity of generated chemical compounds and significant differences between the species. A widespread occurrence of aromatics (toluene, styrene, phenol and 4-methylphenol), acids (acetic acid, benzoic acid alkyl ester derivatives, 2-propenoic acid esters and octadecanoic acid octyl esters) in pyrolysates was detected. Ubiquitous furan-derived products included furfural and 5-methyl-2-furaldehyde. As a pyran-derived compound maltol was obtained by one red algal species (P. rubens) and the monosaccharide d-allose was detected in pyrolysates in one green algal (P. crispa). Further unique chemicals detected were dianhydromannitol from brown algae and isosorbide from green algae biomass. In contrast, the anhydrosugar levoglucosan and the triterpene squalene was detected in a large number of pyrolysates analysed. © 2013 Elsevier B.V. All rights reserved.

In-situ X-ray studies of clean catalytic technologies

The rational design of new heterogeneous catalysts for clean chemical technologies can be accelerated by molecular level insight into surface chemical processes. In-situ methodologies, able to provide time-resolved and/or pressure dependent information on the evolution of reacting adsorbed layers over catalytically relevant surfaces, are therefore of especial interest. Here we discuss the application of in-situ XPS and in-situ, synchronous DRIFTS/MS/XAS methodologies to elucidate the active site in Pd-catalyzed, selective aerobic oxidation of allylic alcohols.

Kinetic modeling studies of heterogeneously catalyzed biodiesel synthesis reactions

The heterogeneously catalyzed transesterification reaction for the production of biodiesel from triglycerides was investigated for reaction mechanism and kinetic constants. Three elementary reaction mechanisms Eley-Rideal (ER), Langmuir-Hinshelwood-Hougen-Watson (LHHW), and Hattori with assumptions, such as quasi-steady-state conditions for the surface species and methanol adsorption, and surface reactions as the rate-determining steps were applied to predict the catalyst surface coverage and the bulk concentration using a multiscale simulation framework. The rate expression based on methanol adsorption as the rate limiting in LHHW elementary mechanism has been found to be statistically the most reliable representation of the experimental data using hydrotalcite catalyst with different formulations. © 2011 American Chemical Society.

In situ studies of structure-reactivity relations in biodiesel synthesis over nanocrystalline MgO

High temperature processing of solvothermally synthesised MgO nanoparticles promotes striking changes in their morphology, and surface chemical and electronic structure. As-prepared NanoMgO comprised ∼4 nm cubic periclase nanocrystals, interspersed within an amorphous Mg(OH)(OCH3) matrix. These crystallites appear predominantly (1 0 0) terminated, and the overall material exhibits carbonate and hydroxyl surface functionalities of predominantly weak/moderate base character. Heating promotes gradual crystallisation and growth of the MgO nanoparticles, and concomitant loss of Mg(OH)(OCH3). In situ DRIFTS confirms the residual precursor and surface carbonate begin to decompose above 300 °C, while in situ XPS shows these morphological changes are accompanied by the disappearance of surface hydroxyl/methoxide species and genesis of O- centres which enhance both the surface density and basicity of the resulting stepped and defective MgO nanocrystals. The catalytic performance in tributyrin transesterification with methanol is directly proportional to the density of strong surface base sites. © 2010 Elsevier B.V. All rights reserved.