OpenUCT :: Browsing by Author "Jackson, Graham Ellis"

Browsing by Author "Jackson, Graham Ellis"

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Open Access
The application of nuclear magnetic resonance in the structural elucidation of natural products
(1994) Nair, Margie May; Jackson, Graham Ellis
Multipulse Nuclear Magnetic Resonance (NMR) techniques were investigated via structural assignment of various natural products. The natural products chosen for investigation of 2D NMR spectroscopy as a structural tool were the opium alkaloids codeine and papaverine, the diterpenoid alkaloids delphinine and aconitine and the triterpenoid derivatives of cucurbitaceae. One dimensional NMR spectroscopy viz 1H, 13C and Distortionless Enhancement by Polarisation Transfer (DEPT) spectroscopy was initially applied to obtain a level of indication of the complexity of the structural problem solving. Various multipulse techniques were chosen depending on the sample quantity available, the sensitivity of the technique, the information provided and its applicabilty in the field of natural products. Both homonuclear scalar and dipolar correlation as well as short and long range heteronuclear correlation was investigated. The homonuclear Correlation Spectroscopy (COSY) experiment which revealed scalar 1H-1H scalar correlations was adequate for the structural assignment. The Heteronuclear Multiple Quantum Coherence (HMQC) experiment offered greater sensitivity on small sample quantities whilst the long range Heteronuclear Correlation (HETCOR) and Heteronuclear Multiple Bond Coherence (HMBC) experiments were essential for complete assignment of the quaternary groups. The stereochemical designation of some of the compounds was confirmed using the Rotating Frame Overhauser Enhancement Spectroscopy (ROESY) experiment which proved to be a more applicable pulse sequence for the natural products under investigation. The 1H and 13C assignments of these derivatives and the experimental approach used to obtain this data was compared to that present in the literature. The results indicate that apart from offering tremendous versatility depending on the special attributes of the compound, two dimensional NMR techniques are imperative for the unambiguous structural assignment of natural products.
Open Access
The application of physicochemical methods for the analysis of small and complex pharmaceutical drugs
(2003) Mabotha, Tebogo E; Ravenscroft, Neil; Jackson, Graham Ellis
The application of physicochemical methods for the analysis of small and complex pharmaceutical drugs was investigated. The methods were applied to small chiral molecules and further extended to analysis of complex glycoconjugate vaccines.
Open Access
Chemical speciation and spatial distribution of heavy metals and their adsorption onto sediments of the Berg River, Western Cape, South Africa
(2014) Benamer, Mustafa Alarabi; Jackson, Graham Ellis; Winter,Kevin
The Berg River, Western Cape, South Africa, is an example of a catchment region where human pressures and conservation of natural resources collide. The river receives effluents from two large settlements and several smaller adjacent villages, including that of industrial and extensive agricultural activity. The estuary is one of the largest in South Africa and rated as the third most important conservation zone in the country. In this study, the chemical speciation of heavy metals in the river sediment was determined in order to evaluate the extent of pollution. Chemical speciation using sequential chemical extraction of sediment samples was used to measure the mobility and bioavailability of cadmium (Cd), lead (Pb), arsenic (As), chromium (Cr), nickel (Ni), cobalt (Co), iron (Fe), copper (Cu), zinc (Zn) and manganese (Mn). The metals Cd and Zn were found to be the most mobile and bioavailable. The study also examined the vertical distribution of heavy metals in estuarine sediment cores to evaluate the extent of heavy metal contamination with time and the degree to which heavy metals are influenced by other sedimentological parameters such as grain size, sediment composition and organic matter. Three sediment cores, ranging from 160 to 240 em long, were collected using a mechanical vibrating corer. The vertical distribution of metals in the cores showed that the metal concentration was higher at the top and middle of the cores. Based on the enrichment factor (EF) and anthropogenic factor (AF) values, it is suggested that the sediments of the estuary are not polluted with Co, Mn, Cu, Ni, Zn and Fe but moderately to highly polluted with Pb, As, Cd and Cr. The data reported provide a useful baseline for establishing heavy metal concentrations in the estuary and will be an important consideration in future sediment quality studies. The spatial distribution of the metals was also studied to understand how location is linked to metal concentration. The average concentration of metals in the core sediment increased with increasing distance from the mouth of the river. The adsorption behaviour of the estuary sediment with micro-pollutants has a significant influence on the environmental quality of estuary waters. For this reason, the absorption of Pb, Cr, Cu, Ni, and Zn onto sediment was study. It was found that the sediments of the Berg River estuary have a low potential for absorption of Ni and Zn making these metals more mobile and bioavailable.
Open Access
Chemogenomic approaches to drug design : docking-based virtual screening of nematode GPCRs for potential anthelmintic agents
(2016) Masuka, Raban Wilfred; Jackson, Graham Ellis; Chibale, Kelly
Among common problems affecting human health and veterinary medicines, helmintic infections are major. The pathogens affect 550-750 Million people worldwide, and affect childhood growth, pregnancies, and development of the intellect. Helminths affects the well-being of animals as well including livestock and reduce the animal populations. However, the current anthelmintics are no longer as effective and some strains have developed resistance thus increasing the need for new anthelmintics. Unfortunately, not too much information is available detailing the physiology of helminths. The published genomic sequence of nematode Caenorrhabdtis elegans as well the primary sequence of the FLP18R1 G-Protein Coupled Receptor are available. GPCRs play a significant role as targets for therapeutics and are responsible for signal transduction in cells. Thus, nematode GPCRs offer an alternative target to design new anthelmintics. Unfortunately, very little information exists about these targets and there are no known x-ray or NMR structures. In this work, the 3D structure of nematode GPCR receptor (FLP18R1) was determined using homology modeling using the beta-2-adrenergic receptor as a template. The homology model developed had 24.87 % sequence identity with the template. Explicit membrane molecular dynamic simulations were used to optimize and refine the helices of the model over 100 ns. The homology model was of acceptable quality.
Open Access
Combined NMR and simulation study of carbohydrate linkage dynamics
(2000) Best, Robert; Naidoo, Kevin; Jackson, Graham Ellis
Biomaterials have recently gained significance as a result of environmental pressures and their increased viability through crop engineering. Starch harvested from maize crops is one example of a cheap and abundant biopolymer, which could substitute conventional polymers such as polyethylene as a material in manufacturing. Its practical application, however, will depend on understanding its physical behaviour, so that intelligent modifications can be made to enhance its properties. The most effective way of changing a polymer's properties is by modification at the chemical level, since ultimately it is this which determines the macroscopic features, such as viscosity, plasticity and tensile strength. Since the origin of these features is difficult to study experimentally, this thesis will tackle the problem by means of computer simulation of small carbohydrate fragments. In particular, the two principal types of carbohydra te linkage (namely 0: (1--+4) and 0: (1--+6)) will be examined in this thesis, since these are the chief elements of conformational flexibility in these molecules. The 0(1--+4) and 0:(1--+6) linkages are studied both separately in the maltose and isomaltose molecules respectively and together in panose and the resultant water structuring and dynamic behaviour are studied. Although the computational approach provides insights not available experimentally, it is nonetheless important to compare the results obtained with an experimental reference as a check on their validity. N!vlR T1 relaxation measurements, which give indirect information on the atomic scale dynamics, have been measured for each of the model fragments and compared with values calculated directly from simulation.
Open Access
Complexation of trivalent lanthanides by three diphosphonate ligands in the blood plasma
(1997) Zeevaart, Jan Rijn; Jackson, Graham Ellis; Jarvis, N V
It has been shown that ¹⁵³Sm complexed with the bone seeking ligand ethylene-diaminetetramethylene phosphonate (EDTMP) is effective in pain palliation therapy of bone cancer. Blood plasma models for this ligand with Sm(III) and Ho(III) have been successfully constructed explaining the differences between ¹⁵³SmEDTMP and ¹⁶⁶HoEDTMP. The latter isotope is preferred because of its more energetic β particle, thought to improve the therapeutic effect of the radiopharmaceutical. However, ¹⁶⁶HoEDTMP is not an effective pain palliation agent and consequently the search for a more effective bone cancer therapeutic radiopharmaceutical involving ¹⁶⁶Ho continues. A ligand is being sought which complexes Ho(III) with a formation constant high enough to survive competition from blood plasma ligands but not so high to prevent ¹⁶⁶Ho from being accessible to metastases. EDTMP is unsuitable as such a ligand because of its inability to compete with citrate for complexation of Ho(III). For this study three diphosphonate ligands applied in radiation imaging of bone or nonradiative treatment of osteoporosis were chosen. They are APD (1-hydroxy-3-aminopropylidene- diphosphonic acid), MDP (methylenediphosphonic acid) and HEDP (1- hydroxy-ethylene-diphosphonic acid). Formation constants for the complexation of Ca(II), Mg(II), Zn(II), Sm(III) and Ho(III) with all of these ligands were measured using potentiometry and polarography. The latter was used to complement potentiometry in systems where precipitates formed. The complexation of Cd(II) by HEDP was used to compare the two techniques and to show that the values found by either technique are comparable. NMR studies were attempted on some complexes in solution to investigate the role the of the hydroxy-group (APD and HEDP) in complexation. The program ECCLES was used together with the formation constants measured in this study to predict the speciation of Ho(III) and Sm(III) with these three ligands in blood plasma. The results gathered for Ho(III) and APD were used as an indication and in an application to an ethical committee before animal testing. A baboon test was carried out using ¹⁶⁶HoAPD, the most promising system. The resulting bone-uptake and side-effects found in the animal study confirmed the predictions made by ECCLES. It proved that ¹⁶⁶HoAPD would be ineffective as a therapeutic agent due to high liver uptake. Valuable information on how a future radiopharmaceutical should be designed was obtained in this study.
Open Access
Computer aided chemical speciation in designing metal-based potential anti-inflammatory agents
(2006) Odisitse, Sebusi; Jackson, Graham Ellis
The objective of this study was to develop copper based anti-inflammatory agents for the treatment of inflammation associated with Rheumatoid Arthritis. Four low molecular ligands, N,Nt-di(aminoethylene)-2,6-pyridine dicarbonylamine (PrDH), Bis-(N,N-dimethylethyl)-2,6-pyridinedicarboxamide (PrDM), N,N'-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (PrDPr) and 3,5-bis[(aminoethyl)ethanediamide]-4-oxahexacyclo-dodecane (PCUA) were designed and synthesised. The formation constants of these ligands with H+, Cu2+, Niz+, Znz+ and Caz+ were determined potentiometrically at 25°C and 0.15 mol dm-3 Na+Cr. The Cu(II) formed relatively more stable complexes than other three metal ions. The structures of the different Cu(II) species formed with these ligands were investigated using nuclear magnetic resonance(NMR), infrared (IR) spectroscopy, ultraviolet-visible (UV-visible) spectroscopy as well as molecular mechanics calculations. For the NMR spectroscopy, results showed that the central pyridyl nitrogen and amide nitrogen(s) as well as the terminal amino/pyridyl groups coordinate to the Cu(II) ion in solution. The IR results indicated that an amide nitrogen is coordinated to the Cu(II). The UV-visible study gave the smooth deconvoluted spectra of the individual species for the Cu(II)-PrDH, Cu(II)-PrDM and Cu(II)-PrDPr systems in support of the potentiometric results. The three studied ligands form tetragonally distorted octahedral MLH-l and MLH-z species with Cu(II). The molecular mechanics was used to calculate the internal strain energies of the different possible geometries of related complex species. A comparison of these energies was used to rationalize the different stabilities of these structures.
Open Access
A computer model of water-in-oil emulsion coagulation
(1996) Seymour, Lisa; Jackson, Graham Ellis
In this thesis, a stochastic computer model of water-in-oil emulsion coagulation, a two stage process of aggregation and coalescence, is presented. The theoretical basis of the model, including equations for the van der Waals, electrostatic and steric energy barriers between dissimilar droplets, is described. Many of these equations have been derived by the author. A chemical speciation study of the aqueous phase typically found in emulsion explosives is presented. A potentiometric investigation of the protonation equilibria of propionate, succinate and mono-methyl succinate in tetraethyl ammonium bromide, ammonium nitrate, sodium nitrate, potassium nitrate and calcium nitrate at 25°C and 3 mol/dm³ ionic strength was performed. Nuclear Magnetic Resonance titrations for succinate and propionate in varying concentrations of the same salts are also shown. A method of converting thermodynamic stability constants from one ionic strength to another using a modified form of the Pitzer equations is presented with a computer program which performs the conversion. A novel method of obtaining complexation constants from protonation constants in varying media is proposed. Using optical microscopy, creaming rates and laser particle sizing, the affects of changing surfactant concentration, salt concentration, pH and shearing time for emulsions of ammonium nitrate solution in heptane with CRILL 43 are shown. Equations are derived for converting creaming rate data to droplet size information and a computer program for converting Malvern light intensity data in the anomalous regime (typical of water-in-oil emulsions) to size distribution data is presented. The computer model is validated against experimental data from this work and the literature and is used to make stability predictions for systems for which no data exists. Further uses for the model are discussed.
Open Access
Computer modelling of the chemical speciation in seawater
(1990) Van der Meulen, Karen; Linder, Peter W; Jackson, Graham Ellis
The primary aim of this thesis is to establish a computer model of the chemical elements in seawater and to use this model to gain insight into the chemical processes controlling dissolution, precipitation, redox levels and coordinative interactions in surface seawater. In order to accomplish this task a relatively extensive database consisting of about 580 complexation equilibria arising from 32 inorganic and 10 organic components has been set up. Constants have been selected from critical compilations. Included in these equilibria are solubility products for the formation of potential solids, redox reactions and interactions with the atmospheric gases carbon dioxide and oxygen.
Open Access
Computer-aided chemical speciation in metal-based drug design
(2002) Nomkoko, Thembelani Edmund; Jackson, Graham Ellis
Formation constants of Cu²⁺, Ni²⁺, Zn²⁺, Ca²⁺ and Gd³⁺ with the polyamine(amide) ligands N,N' -bis(2-hydroxyiminopropionyl) propane-1,3-diamine (L² ) and (1, 15)- bis(N,N-dimethyl)-5, 11-dioxo-8-(N-benzyl)-l ,4,8, 12, 15-pentaazapentadecane (L³ ) as well as those of Gd³⁺ with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L 1 ) were investigated by glass electrode potentiometry at 25°C and an ionic strength (I) of 0.15 mol dm-³.
Open Access
Conformational and docking studies of Gonadotropin releasing hormone and its analogsby NMR spectroscopy and molecular modelling
(1999) Maliekal, James C; Jackson, Graham Ellis
Gonadotropin releasing hormone (GnRH) is a decapeptide with blocked amino and carboxy termini and plays a central role in reproduction. Mammalian GnRH has a positively charged Arg8 residue and binds to the mammalian receptor with high affinity. However, the neutral analog Cln8GnRH has very low affinity. The affinity is restored when the Gly6 is replaced by the achiral D-Trp6, or the Gly6 and Leu7 are modified to form a 6,7 y-lactarn. His5Trp7Tyr8GnRH also shows reasonably high affinity. A comprehensive conformational search was carried out using Nuclear Magnetic Resonance spectroscopy and Simulated annealing to identify the bio-active conformations and to explain the different binding affinities of these peptide analogs. The interproton distances and backbone torsion angles obtained from the NMR data were used to constrain the peptides during the simulated annealing. A large number of structures were generated for each peptide and their conformations analyzed. All live peptides showed some degree of ﬂexibility of conformation, mainly in the terminal domains. The four high affinity analogs all had similar backbones with a β type bend around the Glys residue and the two termini in proximity. The Arg8 in GnRH was involved in several hydrogen bonds that stabilized the folded conformation. In contrast, the inactive Gln8GnRH had a markedly different conformation, with the termini pointing away from each other. The lowest energy structures identified from the simulated annealing were used in subsequent receptor-ligand docking studies. All the high affinity analogs were found to fit neatly into the binding pocket. Arg8 of GnRH formed several H-bonds with residues on the receptor. However, Gln8GnRH showed a poor fit and considerable repulsion between ligand and receptor was evident. The Gln8 did not form H-bonds with the receptor. The calculated binding energies were consistent with the relative binding potencies observed for all ﬁve analogs studied.
Open Access
Copper and rheumatoid arthritis - an in vitro study of metal-protein interactions
(1998) Singh, Manooj; Jackson, Graham Ellis
Acute and Chronic inflammations in Rheumatoid Arthritis are characterized by, among other features, changes in the metabolism of copper. Previous studies have shown that administration of exogenous copper, and the in vivo manipulation of endogenous copper may provide new ways of coping with the problem of anti-inflammatory/anti-arthritic therapies. Computer models of blood plasma have attempted to rationalize the use of copper complexes in this regard. This thesis describes the design and commissioning of an ultrafiltration apparatus to study metal interactions with blood proteins. The results are compared with equilibrium dialysis. The systems studied using this technique includes, the binding of Cu(ll) to HSA and BSA, ternary Cu(ll)-HSA-amino acid systems, as well as competitive studies of the Cu(ll)-HSA system with Mg(ll), Ca(ll) and Zn(ll). The ultrafiltrate was analysed using HPLC and atomic absorption spectroscopy. Protein preparation was found to be important and the different methods used for protein purification were compared using gel electrophoresis and atomic absorption. Binding studies of chelating agents as well as several pharmaceuticals in human blood serum were carried out and compared with computer modelling studies.
Open Access
Copper chelating anti-inflammatory agents of pseudo-mimics of human serum albumin (HSA) : copper and rheumatoid arthiritis
(2006) Zvimba, John Ngoni; Jackson, Graham Ellis
The objective of the study was to develop copper based anti-inflammatory agents for alleviation of inflammation associated with RA.
Open Access
Design of novel copper(II) based anti-inflammatory drugs for the elevation associated with Rheumatoid Arthritis
(2009) Mhlambiso, Zizile; Jackson, Graham Ellis
It has been shown that copper complexes are able to alleviate inflammation associated with Rheumatoid Arthritis (RA). Serum copper levels are elevated in RA and it has been postulated that endogenous copper might have a protective function in chronic inflammatory conditions. In designing Cu(I1) anti-inflammatory drugs, one needs to know the stability constants of the ligand together with Cu(I1) and the competitive metal ions, Zn(I1) and Ca(I1) in blood plasma. For this purpose glass electrode potentiometry, infrared (lR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, UV/Visible spectroscopy as well as blood plasma modelling were used to explore the coordination chemistry of a newly designed ligand, PCUL (Bis-(3- aminoethy-2-aminomethylpyridine )-oxahexacyclo-dodecane). PCUL protonation and formation constants with Cu(I1) and Zn(I1) were investigated by potentiometric analysis at 2SoC and 0.ISmol/dm3 Na + (CI) The potentiometric analysis showed that CU(I1) formed far more stable complexes at physiological pH with PCUL than the in vivo competitor Zn(I1). In this study the IR spectroscopic analysis was used to determine the Cu(I1)-PCUL complexation sequence. The IR spectra show that the central amines are coordinated to the metal ion first. The small frequency shift between pH 4.02 to 6.91 proves that the pyridyl nitrogen atoms are also coordinated to CU(I1).
Open Access
Development of an antirheumatic drug
(1988) Voyi, Kuku Vinolia Vuyelwa; Jackson, Graham Ellis
The diamino-diamide ligands have been investigated in an attempt to develop an antirheumatic drug. The ligands N,N'-di-(2-dimethylamino)ethyloxamide and N,N'di-(2-diethylamino)ethyloxamide, were synthesised and characterised using the physical techniques, NMR, mass- and infrared spectrometry. The stability constants of the complexes of Mg, Ca, Zn and several first transition metal-ions with the ligands were determined potentiometrically. The solution conformation of the CuII complexes were determined using visible spectrophotometry. Finally the physico-chemical studies were carried out. Firstly by studying the interaction of the copper complex with albumin at the physiological pH 7.4 using visible spectrophotometry. Secondly by determining the superoxide dismutase activity of the ligand by reduction of nitrobluetetrazolium using visible spectrophotometry. Lastly the ligands and the carr, CuII, MgII and ZnII metalions were monitored in vitro using the computer blood plasma model.
Open Access
Development of copper based anti-inflammatory drugs: histodine derivatives
(2010) Mohajane, Mamohale; Jackson, Graham Ellis
Methyliminodiacetylhistidine dimethyl ester could not be synthesised. However the other two ligands, glycine and glycyl-L-histidine were purchased and used for this study. The equilibrium constants of the ligand (glycyl-L-histidine) and the ligand complexes with Cu(II), Ni(II) and Zn(II) were investigated with glass electrode potentiometry and isothermal titration calorimetry at 25Â±0.01oC at an ionic strength 0.15M with NaCl. Potentiometric studies show that glycyl-L-histidine has three dissociable protons, and the neutral form of the ligand forms around pH 6.60. Potentiometric results of copper(II) complexes with glycyl-L-histidine were compared to the potentiometric titration of the ligand with Ni(II) and Zn(II). Copper(II) complexes of glycyl-L-histidine were more stable than Ni(II) and Zn(II) complexes of glycyl-L-histidine. The potentiometric results for these systems were in good agreement with the literature results. From the potentiometric studies, the LH form of glycine was more stable than the LH form of glycyl-L-histidine by 1.19 log units. The second protonation of glycyl-Lhistidine is on the imidazole ring and hence there is so comparable protonation site for glycine. Instead the third protonation step of glycyl-L-histidine is comparable to the second protonation step of glycine. The ML form of Cu(II)-glycyl-L-histidine complexes was more stable than that of Cu(II)-glycine complexes by 1.07 log units. ML was the only common species for the two systems. The interaction between copper(II) and glycyl-L-histidine was also studied with isothermal titration calorimetry (ITC) from pH 5 to pH 8. This was compared to a simpler system of glycine. The change in speciation for this method was characterized by the N value. The speciation from ITC results followed that of potentiometric results. The ML species of Cu(II) and glycine formed in acidic solutions, and the ML2 formed in basic solutions. In this pH range, the ML species of Cu(II) and glycyl-L-histidine were the most predominant species in solution. The ITC results agreed with the potentiometric results. At pH 5 where ML was the most predominate species in both the Cu(II)-glycine system and the Cu(II)-glycyl-L-histidine v system (N 1) Log K of the glycyl-L-histidine system was greater than that of the glycine system. The structures of the complexes were predicted with ultraviolet-visible (UV-Vis) spectrophotometry. The visible spectra obtained for the different Cu(II)/Glycyl-Lhistidine species in solution were typical of Cu(II) complexes in a tetragonally distorted, octahedral environment. The molar extinction coefficients are also typical of Cu(II) complexes and reflect the distortion of the metal-ion environment. The sequence of protonation/deprotonation of the ligand was studied with 1H NMR spectroscopy. The first deprotonation of glycyl-L-histidine occurred at very acidic environments, and this was the deprotonation of the carboxylate proton. The second deprotonation occurred at one of the imidazole nitrogens and the last one occurred in highly basic environments. This was the deprotonation of the NH2 terminal. The structure of complexes of Cu(II) with glycyl-L-histidine were also studied by 1H NMR. Form 1H NMR results, the active binding sites for glycyl-L-histidine are the imidazole nitrogens, the amide nitrogen and the terminal NH2 group. The imidazole nitrogen involved in coordination first, followed by the amide nitrogen, followed by the terminal NH2 group The capacity with which the ligand can increase the low molecular weight Cu(II) complexes in blood plasma was studied using a computer model of blood plasma. At reasonable concentrations, the ligand was not able to mobilise endogenous copper. Most of the ligand existed as LH and LH2 in blood plasma. Moreover, glycyl-Lhistidine increased the low molecular weight complexes of Zn(II) more than of Cu(II).
Open Access
The development of creosote macroemulsions to be used for wood preservation
(1999) Nzimande, Aubrey Khethukuthula; Jackson, Graham Ellis; Louwrens, Herman B
Creosote treated timber "bleeds" profusely in hot weather and develops tarry, oily surfaces that are difficult to handle and pose a health hazard. The objective of this work is to investigate the possibility of improving the surface condition of the creosote treated timber. The possibility of using creosote macroemulsions for wood impregnation purposes was investigated. Creosote emulsions also present the possibility of improving other creosote characteristics such as penetration and distribution of creosote in wood during treatment. Creosote emulsions were successfully developed by identifying the suitable class of surfactants (anionic}, chemical type of surfactant (unsaturated fatty acids), and type of emulsion (water-in-oil). However, these emulsions could not improve the surface condition of the creosote treated timber. The penetration and distribution characteristics of both the creosote emulsion and unemulsified creosote were satisfactory. Both the creosote emulsion and the unemulsified creosote penetrated the sapwood completely but there was no penetration into the hardwood.
Open Access
Diamino diamide copper complexes as anti-arthritic agents
(1993) Voyé, Alexander; Linder, Peter W; Jackson, Graham Ellis
This thesis describes the investigation of a series of diamino diamide copper(II) complexes with respect to their potential as anti-inflammatory agents in the treatment of rheumatoid arthritis. Several physico-chemical techniques were employed in the investigation including glass electrode potentiometry, UV/VIS spectroscopy, molecular mechanics calculations, speciation modelling as well as X-ray crystallography. Animal experiments were also carried out.
Open Access
Dipeptides as potential anti-flammatory drugs for rheumatoid arthritis
(2013) Mohajane, Mamohale; Jackson, Graham Ellis
The H⁺ and Cu²⁺ equilibria of four glycine peptides (glycyl-glycine, glycyl-L-leucine, glycyl-L-phenylalanine and glycyl-L-histidine) and four sarcosine peptides (sarcosylglycine, sarcosyl-L-leucine, sarcosyl-L-phenylalanine and sarcosyl-L-histidine) have been studied using glass electrode potentiometry and isothermal titration calorimetry at 25 °C and an ionic strength 0.15 M (NaCl). The terminal amine of the sarcosine peptides is more basic than the glycine analogues. The methyl group on the terminal amine (for sarcosine peptides) does not affect the stability constants of the ML species, significantly. Log K for ML species for all the Cu(II)/peptides complexes ranged between 5.79 and 6.54, except for glycyl-L-histidine that showed log KML = 9.16. Heat accompanying the formation of ML for all the species ranged between -5.1 kcal mol⁻¹ and-6.6 kcal mol⁻¹, except for glycyl-L-histidine that showed ΔHML = -3.6 kcal.mol⁻¹. Structures for the different species in solution were postulated based on nuclear magnetic resonance and ultraviolet-visible spectrophotometry data. Molecular mechanics was used to investigate the possible structures. The minimum energy of the trans form of most the complexes was less than the cis form of the complexes.
Open Access
Effect of composition on empirical stability trends for oil-in-water emulsions
(1996) Wilson, Keith Neville; Jackson, Graham Ellis
Relative stabilities of paraffin oil-in-water emulsions were determined empirically as a function of increasing ionic strength, surfactant type or concentration, droplet size, pH and calcium(II) concentration. Stabilities were measured by droplet size changes, planar interface oil droplet coalescence times, creaming rates and photography. Stability trends between methods were compared. Conclusions were derived in terms of creaming and coagulation. The trends below were discussed in terms of theories of emulsion stability. 1. Increased surfactant concentrations stabilised the emulsions against creaming. Coalescence trends were complex: an optimal cetylpyridinium chloride concentration stabilised the emulsions. Beyond that concentration, stability was reduced. Because of its low HLB, increased sorbitan sesquioleate concentrations destabilised emulsions towards coalescence. 2. Smaller droplets stabilised all the emulsions despite the increased polydispersity. 3. Increased ionic strengths accelerated creaming. Coalescence was faster for cetylpyridinium chloride because of reduced droplet repulsion. Sodium dodecyl sulphate resisted coalescence at all ionic strengths due to the restabilisation predicted by the Stochastic model. 4. pH did not affect emulsions containing a pH-stable surfactant (sodium dodecyl sulphate). Emulsion stability was reduced with acid- or base-labile labile surfactants (sorbitan sesquioleate, cetylpyridinium chloride) due to reduced ability to lower the surface tension during emulsification, or hydrolysis. 5. Ca⁺² destabilised emulsions containing anionic surfadants (sodium dodecyl sulphate and laurate) by co-ordination, but had little effect on a cationic emulsifier (cetylpyridinium chloride) to which it did not co-ordinate. The destabilisation of anionic-based emulsions was due to the formation of oil-wettable solid salts and the removal of the o/w surfactant. 6. Low stabilities of sorbitan sesquioleate-based emulsions were attributed to Bancroft's rule and the low hydrophile-lipophile balance of sorbitan sesquioleate.