OpenUCT :: Browsing by Author "Bourne, Susan A"

Browsing by Author "Bourne, Susan A"

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Open Access
Aqueous Solution Equilibria and Spectral Features of Copper Complexes with Tripeptides Containing Glycine or Sarcosine and Leucine or Phenylalanine
(Multidisciplinary Digital Publishing Institute, 2022-01-10) Vicatos, Giselle M; Hammouda, Ahmed N; Alnajjar, Radwan; Bonomo, Raffaele P; Valora, Gabriele; Bourne, Susan A; Jackson, Graham E
Copper(II) complexes of glycyl-L-leucyl-L-histidine (GLH), sarcosyl-L-leucyl-L-histidine (Sar-LH), glycyl-L-phenylalanyl-L-histidine (GFH) and sarcosyl-L-phenylalanyl-L-histidine (Sar-FH) have potential anti-inflammatory activity, which can help to alleviate the symptoms associated with rheumatoid arthritis (RA). From pH 2–11, the MLH, ML, MLH_-1 and MLH_-2 species formed. The combination of species for each ligand was different, except at the physiological pH, where CuLH_-2 predominated for all ligands. The prevalence of this species was supported by EPR, ultraviolet-visible spectrophotometry, and mass spectrometry, which suggested a square planar CuN₄ coordination. All ligands have the same basicity for the amine and imidazole-N, but the methyl group of sarcosine decreased the stability of MLH and MLH_-2 by 0.1–0.34 and 0.46–0.48 log units, respectively. Phenylalanine increased the stability of MLH and MLH_-2 by 0.05–0.29 and 1.19–1.21 log units, respectively. For all ligands, ¹H NMR identified two coordination modes for MLH, where copper(II) coordinates via the amine-N and neighboring carbonyl-O, as well as via the imidazole-N and carboxyl-O. EPR spectroscopy identified the MLH, ML and MLH_-2 species for Cu-Sar-LH and suggested a CuN₂O₂ chromophore for ML. DFT calculations with water as a solvent confirmed the proposed coordination modes of each species at the B3LYP level combined with 6-31++G**.
Open Access
Beneficiation of selected pesticides and an antihyperlipidemic agent via cyclodextrin complexation and co-crystallization
(2016) Maurel, Vaughan Jean; Caira, Mino R; Bourne, Susan A
The applications of many bioactive molecules are limited by their undesirable physicochemical properties, such as poor aqueous solubility and low thermal stability. The agrochemicals methyl- 2,5-dichlorobenzoate (fungicide, DCB) and fenthion (insecticide), as well as the medicinal compound acipimox (lipid-lowering agent) were selected for study in this context. The cyclodextrin (CD) complexes γ-CD/DCB, 2,6-dimethylated-β-CD/DCB, β-CD/fenthion, permethylated α-CD/fenthion and permethylated β-CD/fenthion, were synthesised. 1H-NMR spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and hot stage microscopy (HSM) were used to assess their stoichiometries and thermal behaviours. The complexes 2,6-dimethylated-β-CD/DCB, permethylated α-CD/fenthion and permethylated β-CD/fenthion have 1:1 host-guest stoichiometries, while those for γ-CD/DCB and β-CD/fenthion are 3:4 and 2:1 respectively. Single crystal X-ray structures were elucidated to investigate the modes of DCB inclusion and crystal packing. All of the solid complexes displayed higher thermal stabilities than those of the untreated pesticides. Furthermore, the volatility of the insecticide fenthion (a liquid at 25 ᵒC) was significantly reduced by its transformation to a solid on CDcomplex formation. The solution-state behaviour of fenthion was qualitatively evaluated using UV-visible spectrophotometry and induced circular dichroism. Phase solubility profiles at 25 ᵒC were of type Bs for solubilisation of DCB by β-CD and (2-hydroxypropyl)-β-CD, and for solubilisation of fenthion by β-CD, the respective 1:1 association constants being 737 ± 108 M⁻¹, 412 ± 53 M⁻¹ and 789 ± 170 M⁻¹. For solubilisation of fenthion by (2-hydroxypropyl)-β-CD and randomlymethylated β-CD, AN- and AP-type behaviours were recorded respectively, with association constants 1863 ± 26 M⁻¹ and 3582 ± 106 M⁻¹ respectively. Eight multi-component crystalline systems (co-crystals and salts) of acipimox were isolated via its reaction with co-formers 4-aminobenzamide, 4-aminopyridine, benzamide, isonicotinamide, tranexamic acid and urea. NMR spectroscopy revealed 1:1 stoichiometries for all products. Their designation as salts or co-crystals was based on unequivocal evidence gleaned from single crystal X-ray structural studies, these assignments being confirmed by infrared spectroscopy. The melting points and decomposition temperatures of the products containing the coformers 4- aminobenzamide, 4-aminopyridine, isonicotinamide and tranexamic acid were significantly higher than those of untreated acipimox. Equilibrium aqueous solubilities of the multicomponent systems ranged from 0.31 to 2.77 times those of untreated acipimox.
Open Access
Carboxylate metallogels - an adventure in supramolecular chemistry
(2018) Zacharias, Savannah Clare; Bourne, Susan A; Ramon, Gaëlle
The field of supramolecular gels has attracted a great deal of attention as these versatile materials have been shown to be highly tunable and responsive to stimuli making them attractive for a multitude of potential applications such as drug delivery, energy and gas storage, and waste water treatment. Serendipity still plays a role in gel discovery. However, with the ever growing library of gels, design is becoming a greater possibility. Interactions involved in the formation of gels are closely related to those in the field of crystal engineering. There are two parts to this body of work. The first follows the exploration of factors that in uence carboxylate gel formation. The second is to examine the response of the iron(III)-carboxylate metallogels to external stimuli. For the gel formation, a range of small carboxylic acids (ligands), solvents, metal salts, and temperatures were used to investigate their respective roles. Systematic study showed that gels from ligands with carboxylate moieties in the ortho position passed the "inverted vial test" most consistently. Of the solvents used, only those with polarities between 4 and 7.2 resulted in gel formation. In general, the rate of gel formation increased with an increase in temperature. It was found that the nature of the counter ion in uences the outcome of gelation. Inorganic counter ions such as nitrate and halides resulted in gel formation, while organic counter ions such as acetylacetonate and oxalate did not. Characterisation was performed using thermal analysis, Fourier transform-infrared spectroscopy, microwave plasma atomic emission spectroscopy, scanning electron microscopy, and powder X-ray diffraction. It was found that the gels were ca. 95-99% solvent. The creation of xerogels, by oven or freeze drying, allowed for better characterisation. The response of the gel to stimuli was explored and they were shown to interact with their environment. Dyes bromocresol green and methyl orange were both sorbed, in different amounts, by the two carboxylate-iron(III) metallogels, Fe-5nite-DMF and Fe-tri-DMF. This was monitored using UV-visible spectrophotometry. Gas sorption experiments were performed using carbon dioxide, hydrogen, nitrogen, and water vapour. This was done in order to determine the response of selected xerogels to gas as well as to examine the effect of the drying method on pore size and gas sorption capability. In all cases, water vapour was adsorbed in the greatest quantity. A range of 184.54 cm³ (STP) g⁻¹ to 577.36 cm³ (STP) g⁻¹ at a relative pressure of 0.760 was seen. Separation of compounds with similar boiling points was attempted using Fe-phens-EtOH, Fe-tri-EtOH, and Fe-5nite-EtOH. The compounds, 2- and 3-methylpiperidine, disrupted the stabilising interactions within the gel and no separation took place. During the investigation into the role of an organic counter ion in gel formation, three novel crystal structures were obtained from iron(III) acetylacetonate and 2,6-pyridinedicarboxylic acid. The structures elucidated were found to be dependent on the temperature and length of time allowed for the reaction. Multiple factors in uence gel formation and with a better understanding of these, tunable materials for specific applications may be created.
Open Access
Characterisation and topological analysis of novel metal-organic frameworks
(2011) Davies, Kate; Bourne, Susan A; Oliver, Clive L
The investigation of complexes in the solid state has developed exponentially over the past few decades in terms of both crystal engineering and supramolecular chemistry. The preparation of new metal-organic frameworks and coordination polymers has been of particular interest due to the large variety of structural topologies as well as the varying functionalities they offer. A study of the preparation of new metal-organic frameworks from common starting materials was undertaken to increase the understanding of the preparative methods for these compounds.
Open Access
Chiral carboxylic acids and their effects on melting-point behaviour in co-crystals with isonicotinamide
(2008) Lemmerer, Andreas; Ba´thori, Nikoletta B; Bourne, Susan A
The crystal structures of co-crystals of two systems of chiral carboxylic acids, optically active and racemic 2-phenylpropionic acid and 2-phenylbutyric acid, with isonicotinamide are reported to investigate the effects of the chirality of the chiral carboxylic acids on the melting point of the co-crystal complexes. It was found that the racemic co-crystal has a higher melting point than the optically active co-crystal, which correlates with the denser packing arrangement inherent in centrosymmetric space groups.
Open Access
Complexation between cyclodextrins and phenylurea herbicides in solution and in the solid state
(2009) Smith, Vincent Joseph; Caira, Mino R; Bourne, Susan A
The author undertook the preparation of cyclodextrin inclusion complexes of four phenylurea herbicides (metobromuron, monolinuron, monuron and fenuron) using the kneading and co-precipitation methods in the solid state while also determining complex formation of the same phenylureas in solution with selected cyclodextrins. The kneading experiments were carried out first to determine whether the phenylureas would complex in the solid-state. The phenylureas were then subjected to complexation by means of co-precipitation under different conditions of crystallisation such as temperature and solvent medium in order to isolate more than one CD complex containing the same host and guest. The solution-state experiments were performed to see if the phenylurea complexes exist in solution and if so, to determine their nature.
Open Access
Computer simulation of nickel in blood-plasma following the in vitro investigations of complex formation chemistry with polyamine(amide) ligands
(Royal Society of Chemistry, 2004) Nomkoko, Edmund T; Jackson, Graham E; Nakani, Bandile S; Bourne, Susan A
In- and out-of-cell potentiometric techniques have been used to determine the formation constants for nickel(II) with 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (L1), N,N′-bis(2-hydroxyiminopropionyl)propane-1,3-diamine (L2) and 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (L3) at 25 °C and an ionic strength of 0.15 mol dm−3. Nickel(II) forms stable complexes with L1 and L2 where square-planar [NiLH−1] and [NiLH−2] species predominate under alkaline conditions. The square-planar coordination of nickel by L1 has been confirmed by a single-crystal X-ray structure, UV/Vis spectrometry and molecular mechanics calculations of the [NiL1H−1] complex. The introduction of a third amine group into L3 dramatically decreases the ligand's ability to complex Ni(II). This results from a change in structure of the complex which decreases the ability of the metal ion to promote the dissociation of the amide protons. Using a model of blood plasma, the high binding ability of L1 towards Ni(II) is calculated to decrease the mobilisation of Cu(II) in plasma by approximately 65%. [CuL1H−1] is currently under investigation as an anti-inflammatory agent.
Open Access
Crystal engineering of dynamic metal organic frameworks for applications in chromic sensing and capturing of small molecules
(2014) Mehlana, Gift; Bourne, Susan A; Ramon, Gaëlle
Crystal engineering of metal organic frameworks (MOFs) has developed rapidly over the years. This has been fuelled by useful properties endowed by these materials. MOFs present a unique platform to control chemical and physical properties through manipulation of the components that construct these materials. In this thesis a series of MOFs prepared from 3-(4-pyridyl)benzoate or 4-(4-pyridyl)benzoate with Co(ll), Zn(ll) and Ni(ll) are presented. Most materials were synthesised under solvothermal conditions. The link between the phenyl and pyridyl ring in the ligand allows for conformational change through varying the dihedral angles between these two parts. The carboxylate moiety can also rotate relative to the phenyl ring and its ability to assume different coordination modes under different environments is of utmost importance in achieving flexibility for the design. Structural elucidation of compounds was performed by single crystal X-ray diffraction. Topological analysis was performed on the networks formed by the compounds to have a better understanding of the network connectivity. Bulk material was characterised by thermal methods such as thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), variable temperature powder X-ray diffraction (PXRD) studies and by hot stage microscopy (HSM). Thermochromic and solvatochromic properties of the activated phases were investigated by spectroscopic techniques. Dynamic motion of the networks upon guest loss and absorption by activated phases were evaluated by single crystal X-ray diffraction studies using Pawley fitting methods. Standard kinetic models were used to analyse the kinetics of guest uptake from isothermal experiments. Non-isothermal experiments were conducted using the TGA and the activation energies were determined for guest desolvation using the Ozawa and Flynn method.
Open Access
Crystal engineering of novel organic-inorganic compounds of N- and O-donor dipyridyl ligands
(2006) Moitsheki, Lesego J; Bourne, Susan A; Nassimbeni, Luigi R
Crystal engineering based upon organic-inorganic compounds has made rapid progress in recent years. These compounds are known to combine the inherent advantages of both organic and inorganic substances. In this thesis, a range of metal compounds were investigated. These include compounds of actinides, lanthanides, transition and main group metals using dipyridyl ligands (4,4'-bipyridine-N,N'-dioxide (bpdo), 1,2-bis(4-pyridyl)ethane (BPE) and 1,2-di(4-pyridyl)ethylene (OPE) Compounds prepared were characterised by x-ray diffractometry. Thermal analysis (thermogravimetry (TG), differential scanning calorimetry (DSC) and hot stage microscopy (HSM)) was used to determine the thermal behaviour of these compounds. Microanalysis was used to confirm elemental composition.
Open Access
Development of dermally absorbed copper(ii) complexes as potential anti-inflammatory drugs
(2021) Vicatos, Giselle Marianthi; Jackson, Graham E; Bourne, Susan A
Rheumatoid arthritis (RA) is a debilitating disease affecting 5% of the world's population and there is no cure. Copper(II) complexes have been reported to have anti-inflammatory activity and alleviate the symptoms associated with the disease. The present study focuses on the design of new drugs that could be used to change the bioavailability of copper(II) and hence alleviate the inflammation. The tripeptides, glycyl-L-leucyl-L-histidine (GLH), sarcosyl-L-leucyl-Lhistidine (Sar-LH), glycyl-L-phenylalanyl-L-histidine (GFH) and sarcosyl-L-phenylalanyl-Lhistidine (Sar-FH) were designed to resemble the natural in vivo copper(II) transporter, human serum albumin, so that they could be selective for copper(II). The preferred route of administration is dermal absorption and so sarcosine was added to improve the lipophilicity of the drug. This administration method was chosen since it is both nonharmful and convenient for patients. The stability of the complexes was measured using glass electrode potentiometry and their solution structure studied using UV-Vis spectrophotometry, CW-EPR spectroscopy, 1H NMR, ESI-MS and molecular modelling calculations. The presence of sarcosine did not significantly affect the stability of the complexes. Several species were found to exist in solution depending on the pH, but at pH 7, the CuLH-2 species predominated for all four tripeptides. In this species, the ligand was found to coordinate to copper(II) via the terminal amine-N, the two amide-Ns and imidazole-N, in a square planar geometry. Using a computer model of blood plasma, all four ligands were found to mobilise copper(II), without disrupting the homeostasis of nickel(II), zinc(II) or calcium(II) in the order of GFH > Sar-FH > GLH > Sar-LH. GFH increased the low molecular mass copper(II) species by 40.7 times at 0.1 mM. The lipophilicity of the complexes was estimated by measuring their octanol/water partition coefficients. All the complexes were found to be hydrophilic with log Poct/aq ranging from -3 to -2. Dermal absorption was estimated using an artificial membrane and a Franz cell. Only a moderate increase in membrane permeability of copper(II) was found. The stability of the copper(II) complexes, their ability to mobilise copper(II) from endogenous sources and their improved dermal absorption, justifies further testing of this class of ligand as potential, dermally absorbable, anti-inflammatory drugs.
Open Access
Development of Pd(II)- and Pt(II)-based catalysts for polymerisation and oligomerisation of [alpha]-olefins
(2001) Ndlovu, Mazwi Eugene; Moss, John R; Bourne, Susan A
The polymers were investigated by DSC and TGA to determine their melting point endotherms and thermal stability. All polymers exhibited low thermal stabilities and low melting point endotherms.
Open Access
Halogen···Halogen interactions in host - guest systems
(2017) Amombo Noa, Francoise Mystere; Nassimbeni, Luigi R; Bourne, Susan A
For a few decades now, halogen bonds which are non-covalent interactions, have gained a lot of interest in the science community due to their applications in diverse research areas. Halogen bonding (XB) is an interaction that occurs between electron deficient halogen compounds and electron donors. This is an established non-covalent interaction in the solid and gaseous phase. In this thesis, the work presented deals with the investigation of halogen bond interactions in host-guest complexes utilising both experimental and theoretical techniques. Two host compounds, tetrakis-4-(bromophenyl)ethylene and its iodo-analogue were synthesised for the studies reported in Chapter 3, 4 and 5. Chapter 3, deals with the classification of halogen···halogen interactions using halogenated methanes as guest solvents. Here, the inclusion complexes can be classified into different types of halogen bonds depending on their geometry. Type I, which are of van der Waals in nature usually have X···X distances greater than the sum of their van der Waals radii. Type IIa and IIb are interactions which are considered to be attractive and their X···X distances are usually shorter than those of type I. The compounds obtained in Chapter 3 were used to study both the kinetics of desolvation and the kinetics of enclathration for the solid host-methyl iodide vapour reactions, to obtain their rate law and determine activation energies. In Chapter 4, the two hosts mentioned above were utilised to form inclusion compounds with a series of halogenated compounds for guest exchange reactions. The structures of the starting inclusion compounds were exposed to the vapours of the second incoming guests to form intermediate complexes and final compounds, which were used to analyse the halogen···halogen interactions in their structures. NMR spectroscopy was performed on selected crystals to monitor the guest exchange experiment and the rate law of each exchange reaction was established. Tetrakis-4-(bromophenyl)ethylene and its iodo-analogue were also used as host compounds in Chapter 5. Here, halogen···halogen interactions are also classified and two novel polymorphs of tetrakis-4-(iodophenyl)ethylene with 3-picoline (3PIC) are reported. Kinetics of enclathration by suspension was conducted on two of the bromohost inclusion compounds (with 3-bromopyridine and 3-picoline) at 25 °C and 35 °C. Competition between hydrogen and halogen bonding was performed in Chapter 6, using three similar but subtly different host compounds with halogenated substituted pyridines as guests. IR spectroscopy and Hirshfeld surface analysis were utilised for further characterisation of these inclusion compounds. The synthesis of halogenated Werner clathrates containing Cl-, Br- and I- in Chapter 7, was conducted with various guests of substituted pyridines. Compounds, which were derived from NiI₂ yielded ionic complexes, forming iodide anions. Iodine was added to these complexes to form tri-iodide anions. The Werner clathrates obtained with the 4-picoline (4PIC) could also be directly synthesised by the exposure of NiCl₂/NiBr₂ to the vapour of 4PIC. Kinetics of enclathration of these two solid-vapour reaction compounds were also analysed. All the structures in this study were elucidated using single crystal X-ray diffraction. Thermal analyses such as thermogravimetry (TG), hot stage microscopy (HSM) and differential scanning calorimetry (DSC) were used for the determination of the thermal behaviour of the new compounds. Variable temperature powder X-ray diffraction was also carried out for the characterisation of the new compounds.
Open Access
Inclusion compounds of multipedal hosts
(1997) Nash, Katherine Lindsay Gifford; Bourne, Susan A; Nassimbeni, Luigi R
The inclusion properties of three multipedal host compounds have been investigated. The host compounds : hexakis(3-hydroxy-3,3-diphenyl-2-propynyl)benzene (host 1), 1,2,3,5,6, 7-hexakis(3-hydroxy-3,3-diphenyl-2-propynyl)naphthalene (host 2), and tetra(3-hydroxy-3,3-diphenyl-2-propynyl)ethylene (host 3), are characterised by a planar electron-rich central region with bulky substituent groups attached to it. Each substituent contains a hydroxyl group capable of hydrogen bonding. These features enable the inclusion of small organic solvent molecules, with suitable functional groups, within the host framework. The crystal structures of selected inclusion compounds and the a-phases of hosts 1 and 3 are presented. The hydrogen bonding patterns and host-guest interactions are analysed. The packing motif of the host compounds and host conformation within each structure is also discussed. The thermal decomposition behaviour of these compounds was investigated using thermogravimetry and differential scanning calorimetry. The kinetics of desolvation for some of the inclusion compounds was determined using isothermal thermogravimetry. Rate laws describing the desolvation mechanisms are ascribed, and the activation energies determined.
Open Access
New crystalline forms of permethylated β-cyclodextrin
(Royal Society of Chemistry, 2004) Caira, Mino R; Bourne, Susan A; Mhlongo, Welcome T; Dean, Pamela M
Two new crystalline forms of permethylated β-cyclodextrin are reported that contain methylglucose residues exclusively in the 4C1 conformation, in contrast to the known monohydrate, in which a single methylglucose residue adopts the 1C4 conformation.
Open Access
Physicochemical studies of the inclusion of selected agrochemicals in cyclodextrins
(2011) Cruickshank, Dyanne Louise; Caira, Mino R; Bourne, Susan A
Pesticides frequently display adverse properties such as low aqueous solubility, low stability, and high toxicity that limit their applications and render them environmentally hazardous. The possibility of improving these physical properties was attempted by complexing four pesticides with native and derivatised cyclodextrins (CDs). The pesticides studied included: the phenylurea herbicide, cycluron; an organochlorine insecticide, endosulfan; an organophosphorus insecticide, fenitrothion; and the chloroacetanilide herbicide, acetochlor. A study of CD complexation with these pesticides in solution as well as in the solid state was undertaken. A further set of experiments was conducted, whereby the thermal stabilities of three isostructural inclusion complexes were evaluated using thermogravimetric analysis.
Open Access
Preformulation solid-state supramolecular beneficiation of selected active pharmaceutical ingredients and a novel drug candidate
(2018) Noonan, Terence James; Caira, Mino R; Bourne, Susan A
The aim from the outset of the project on which this thesis is based was to make use of contemporary methods in the field of supramolecular chemistry to improve the suboptimal physicochemical properties of selected compounds for use in the formulation of pharmaceutical products. The compounds selected were: Clevudine, an established drug that is currently in use for the treatment of chronic hepatitis B infections, 6-(3- (Methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-imidazo[1,2-b]pyridazine (MMV652103), a novel antimalarial drug candidate that displayed good in vitro potency against multidrug resistant and sensitive plasmodial strains and ()-α-lipoamide, a bioactive antioxidant that is currently in use for the clinical treatment of diabetic neuropathy and has other potential uses e.g. as an antiretroviral agent. The methods utilised in pursuit of novel solid-state forms of the compounds included a combination of crystal engineering and experimental screening for polymorphs, solvates/hydrates, cyclodextrin (CD) inclusion complexes, pharmaceutical salts and co-crystals. Screening involved grinding and co-precipitation methods. Characterisation of new forms involved thermal analytical methods including hot stage microscopy (HSM), differential thermal analysis (DTA), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and variable temperature powder X-ray diffraction (VTPXRD). In all cases where single-crystals of adequate quality and size were successfully prepared, the crystal structures were elucidated by single-crystal X-ray diffraction. Molecular conformations, inter- and intramolecular interactions and packing arrangements of crystals were characterised. Polymorphism of clevudine was addressed for the first time. Three polymorphs of clevudine were isolated and characterised in terms of crystal structures and thermal behaviour. The solubility and thermodynamic stability ranking of the three forms was established and schematic energy-temperature diagrams were constructed through the use of the thermal methods listed above, solvent-mediated transition experiments and by kinetic solubility experiments. Characterisation by infrared (IR) spectroscopy has made it possible to promptly and effortlessly identify each form. Multiple novel solid-state forms of the antimalarial drug candidate MMV652103 were produced including four polymorphs, a hydrate, five co-crystals and a salt. The solubility and thermodynamic stability ranking of the polymorphs was established through thermal analysis and kinetic solubility experiments. An amorphous form showed an improvement in dissolution rate, with a concentration 3-4 times that of the crystalline forms after one hour. The designation as co-crystals or salts was accomplished through the use of single crystal X-ray structural analysis and confirmed by IR spectroscopy. Stoichiometry was determined by 1 H - nuclear magnetic resonance (NMR) spectroscopy. A customised solubility experiment was carried out to compare the dissolution rates of the various multi-component forms of MMV652103 in an environment simulating the human duodenum. An enhancement of the dissolution rate was observed with a maximum concentration 4.7 times higher for the co-crystal than for the untreated active compound. Inclusion complexation of ()-α-lipoamide with native CDs (α-, β-, and γ-CD) was confirmed by comparison of putative PXRD traces with those of known isostructural series. Novel complexes were synthesised with the above mentioned native CDs as well as with three derivatised CDs (TRIMEA, DIMEB and TRIMEB). The crystal structures were characterised by single-crystal X-ray diffraction. Host-guest stoichiometries were determined by 1 H-NMR spectroscopy and validated by the ratio of mass loss through TGA. Water composition, melting points and thermal stability in terms of decomposition and guest loss temperatures of the complexes were determined by means of the appropriate thermal methods (DTA, TGA, DSC, HSM). Phase solubility experiments were carried out and showed solubility enhancements for the bioactive compound ranging from a 1.8 fold increase with α-CD to a 7.4 fold increase with randomly methylated β-CD.
Open Access
Progressive design and self-assembly of supramolecular architectures : based on metallamacrocyclic nickel(II) complexes with bipodal tetra-alkylaroylbis (thioureas)
(2004) Hallale, Oren; Bourne, Susan A; Koch, Klaus
Rationally designed bipodal3,3,3',3'-tetraalkyl-l,1'-benzoylbis(thioureas) are used as pre-programmed cheiating ligands to form metallamacrocyclic square planar nickel(ll) complexes via self-assembly. Metal : ligand stoichiometries of either 2:2 or 3:3 can be achieved by using meta- or para- substituted ligands. The metallamacrocyclic complexes are subsequently converted into octahedral adducts via the addition of monodentate nitrogen donor ligands. Metallamacrocycles are further employed as secondary building units in the self-assembly of I-dimensional double- or tripleconnected coordination polymers. The synthesis of these polymers is achieved with the use of exo-bidentate nitrogen donor ligands.
Open Access
Reactions of halogens with Pt(II) complexes of N-alkyl- and N,N-dialkyl-Nʹ -benzoylthioureas: oxidative addition and formation of an I₂ inclusion compound
(2005) Westra, Arjan N; Bourne, Susan A; Esterhuysen, Catharine; Koch, Klaus R
The treatment of cis-[PtII(L1a/b-S,O)2] complexes of N,N-diethyl- (HL1a) and N,N-di(n-butyl)-N'-benzoylthiourea (HL1b) with I2 or Br2 in chloroform, leads to rapid oxidative addition to yield several geometric isomers of [PtIV(L-S,O)2X2] (X = I, Br); the reactions can be monitored by 195Pt NMR and UV-visible spectrophotometry. The products cis-[PtIV(L1a-S,O)2I2] 6 and cis-[PtIV(L1a-S,O)2Br2] 7, which have been isolated and structurally characterized, are the first-reported crystal structures of complexes of Pt(IV) with this class of ligand. Molecules of 6 pack such that the I–Pt–I axes are essentially aligned, with unusually close nearest-neighbour iodide contacts (3.553(1) A˚ ). These short I···I intermolecular interactions lead to infinite chains of weakly connected molecules in crystals of the compound. No such interactions are evident in the corresponding crystals of 7. Reaction of the Pt(II) complex of N-propyl-N'-benzoylthiourea (H2L2a) cis-/trans-[PtII(H2L2a-S)2Br2] with Br2 also results in oxidative addition, to yield trans-PtIV(H2L2a-S)2Br4 9. By contrast, treatment of cis-/trans-[PtII(H2L2a-S)2I2] with I2 does not lead to an oxidative addition product, yielding instead an interesting iodine inclusion compound of PtII, trans-[PtII(H2L2a-S)2I2]·I2 8. In 8, short intermolecular I···I distances of 3.453(1) A˚ between I2 and coordinated iodide ions in trans-[PtII(H2L2a-S)2I2] molecules, result in infinite chains of weakly linked trans-[PtII(H2L2a-S)2I2] ···I2 groups in the lattice. However, the empirically estimated bond order of 0.75 for the included I2 molecules does not support the possible existence of discrete tetraiodide ions (I42−) in the lattice of compound 8.
Open Access
Structures and thermal analyses of Werner clathrates and coordination polymers
(2001) Kilkenny, Mairi; Nassimbeni, Luigi R; Caira, Mino R; Bourne, Susan A
The crystal structures of several organometallic host complexes and their inclusion compounds with small, polar, organic guests have been elucidated. These compounds form a diverse range of structure types, from hydrogen bonded networks of Werner-type inclusion compounds to one- and two- dimensional coordination polymers. Depending on the packing arrangement of the host molecules in the clathrate, the guest molecules (G) may become trapped in cages, stacked in one-dimensional channels or sandwiched between layers of host molecules. Examples of all three clathrate types can be found in the different inclusion compounds presented here. The crystal structures of several organometallic host complexes and their inclusion compounds with small, polar, organic guests have been elucidated. These compounds form a diverse range of structure types, from hydrogen bonded networks of Werner-type inclusion compounds to one- and two- dimensional coordination polymers. Depending on the packing arrangement of the host molecules in the clathrate, the guest molecules (G) may become trapped in cages, stacked in one-dimensional channels or sandwiched between layers of host molecules. Examples of all three clathrate types can be found in the different inclusion compounds presented here. The crystal structures of twelve Werner clathrates and four coordination polymers were solved using single crystal x-ray diffraction techniques. In addition, all compounds were characterised by thermal analysis techniques, including differential scanning calorimetry, thermogravimetry and hot-stage microscopy.
Open Access
Supramolecular modification of selected antitubercular drugs
(2010) Li, Jinjing; Caira, Mino R; Bourne, Susan A
The author's objective was to prepare new solid phases of the antitubercular drug isoxyl [specifically polymorphs, solvates, cyclodextrin (CD) inclusion complexes and cocrystals] and to isolate and characterise a range of solvated forms of the rifamycin antibioticsrifampicin and rifaximin.