Studies in South African marine molluscan chemistry
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
Studies on bioflocculants produced by three freshwater Actinomycetes (Streptomyces Sp.Gansen, Cellulomonas Sp,Bola and Brachybacterium Sp, UFH) isolated from Tyume river
- Authors: Oladele, Agunbiade M
- Date: 2011
- Subjects: Flocculation Streptomyces Gram-positive bacteria Actinobacteria
- Language: English
- Type: Thesis , Masters , Degree
- Identifier: http://hdl.handle.net/10353/6550 , vital:30552
- Description: Several bacteria were isolated from the bottom sediments of Tyume River and investigated for bioflocculant production potentials. Kaolin clay suspension (4 g/l) was used to measure the flocculating activity and three of the positive isolates were identified by 16S rRNA gene nucleotide sequence analyses and the sequences deposited in GenBank as Streptomyces sp Gansen (accession number HQ537129), Brachybacterium sp UFH (accession number HQ537131.), and Cellulomonas sp Bola (accession number HQ537132). Streptomyces sp Gansen exhibited its maximum flocculating activity using lactose (85% activity), peptone (76.3% activity), Ca2+ as sole sources of carbon, nitrogen and cations respectively, and at a neutral pH of 7.0, while, the bioflocculant produced by Brachybacterium sp UFH with glucose, urea and Ca2+ as carbon, nitrogen and cations sources yielded 82% and 97% flocculation activity respectively at a neutral pH. Also, glucose (73.2% activity), ammonium chloride (78.2% activity) and Ca2+ resulted in optimal production of bioflocculant by Cellulomonas sp Bola, also at a neutral pH. Chemical analysis confirmed that bioflocculant produced by Streptomyces Gansen is a polysaccharide while Brachybacterium sp UFH and Cellulomonas sp Bola produces a glycoprotein compound. This freshwater actinomycetes appears to have a tremendous potential as sou rces of new bioflocculants.
- Full Text:
- Date Issued: 2011
- Authors: Oladele, Agunbiade M
- Date: 2011
- Subjects: Flocculation Streptomyces Gram-positive bacteria Actinobacteria
- Language: English
- Type: Thesis , Masters , Degree
- Identifier: http://hdl.handle.net/10353/6550 , vital:30552
- Description: Several bacteria were isolated from the bottom sediments of Tyume River and investigated for bioflocculant production potentials. Kaolin clay suspension (4 g/l) was used to measure the flocculating activity and three of the positive isolates were identified by 16S rRNA gene nucleotide sequence analyses and the sequences deposited in GenBank as Streptomyces sp Gansen (accession number HQ537129), Brachybacterium sp UFH (accession number HQ537131.), and Cellulomonas sp Bola (accession number HQ537132). Streptomyces sp Gansen exhibited its maximum flocculating activity using lactose (85% activity), peptone (76.3% activity), Ca2+ as sole sources of carbon, nitrogen and cations respectively, and at a neutral pH of 7.0, while, the bioflocculant produced by Brachybacterium sp UFH with glucose, urea and Ca2+ as carbon, nitrogen and cations sources yielded 82% and 97% flocculation activity respectively at a neutral pH. Also, glucose (73.2% activity), ammonium chloride (78.2% activity) and Ca2+ resulted in optimal production of bioflocculant by Cellulomonas sp Bola, also at a neutral pH. Chemical analysis confirmed that bioflocculant produced by Streptomyces Gansen is a polysaccharide while Brachybacterium sp UFH and Cellulomonas sp Bola produces a glycoprotein compound. This freshwater actinomycetes appears to have a tremendous potential as sou rces of new bioflocculants.
- Full Text:
- Date Issued: 2011
Study of protein complexes via homology modeling, applied to cysteine proteases and their protein inhibitors:
- Tastan Bishop, Özlem, Kroon, Matthys
- Authors: Tastan Bishop, Özlem , Kroon, Matthys
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148070 , vital:38707 , DOI: 10.1007/s00894-011-0990-y
- Description: This paper develops and evaluates large-scale calculation of 3D structures of protein complexes by homology modeling as a promising new approach for protein docking. The complexes investigated were papain-like cysteine proteases and their protein inhibitors, which play numerous roles in human and parasitic metabolisms. The structural modeling was performed in two parts. For the first part (evaluation set), nine crystal structure complexes were selected, 1325 homology models of known complexes were rebuilt by various templates including hybrids, allowing an analysis of the factors influencing the accuracy of the models. The important considerations for modeling the interface were protease coverage and inhibitor sequence identity. In the second part (study set), the findings of the evaluation set were used to select appropriate templates to model novel cysteine protease-inhibitor complexes from human and malaria parasites Plasmodium falciparum and Plasmodium vivax. The energy scores, considering the evaluation set, indicate that the models are of high accuracy.
- Full Text:
- Date Issued: 2011
- Authors: Tastan Bishop, Özlem , Kroon, Matthys
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148070 , vital:38707 , DOI: 10.1007/s00894-011-0990-y
- Description: This paper develops and evaluates large-scale calculation of 3D structures of protein complexes by homology modeling as a promising new approach for protein docking. The complexes investigated were papain-like cysteine proteases and their protein inhibitors, which play numerous roles in human and parasitic metabolisms. The structural modeling was performed in two parts. For the first part (evaluation set), nine crystal structure complexes were selected, 1325 homology models of known complexes were rebuilt by various templates including hybrids, allowing an analysis of the factors influencing the accuracy of the models. The important considerations for modeling the interface were protease coverage and inhibitor sequence identity. In the second part (study set), the findings of the evaluation set were used to select appropriate templates to model novel cysteine protease-inhibitor complexes from human and malaria parasites Plasmodium falciparum and Plasmodium vivax. The energy scores, considering the evaluation set, indicate that the models are of high accuracy.
- Full Text:
- Date Issued: 2011
Study South Africa
- International Education Association of South Africa (IEASA), Jooste, Nico
- Authors: International Education Association of South Africa (IEASA) , Jooste, Nico
- Date: 2011
- Subjects: Education, Higher -- South Africa , Universities and colleges -- South Africa , Technical Institutes -- South Africa , Vocational guidance -- South Africa
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/64952 , vital:28639 , ISBN 9780620512244
- Description: [Extract from article by Ms Merle Hodges]: Over the past year there have been numerous conferences dealing with one general topic. How is it possible for higher education, globally, to produce the same quality in its graduates, research and community outreach when the financial resources entering into the system are radically declining? The conclusion is overwhelmingly despondent. ‘Universities have to do more with less, academics and academic research will increasingly be pressurised by lower salaries internally and career temptations from the corporate world – the impact of which is the greater commodification of universities, and the inevitable decline in academic freedom.’ This global negativity is predicated on inter–related factors. The first, the long tail of the economic recession, is continuing to bite all sectors and higher education is no exception. Secondly, higher education is a little like marketing – when the pressure is on government, sectors like higher education are de–prioritised. In light of this, the position of internationalisation in higher education might seem to fade into the background. Interestingly, the inverse is true. While the zeitgeist of higher education generally appears dismal, the prospects of internationalisation appear rosy in comparison. I believe this is true because of two overlapping issues. Firstly, students are not going to give up on university because of a lingering economic downturn. What they are doing, however, is deciding to travel and study at destinations that would have been perceived as implausible a few years ago. Venezuela, Chile, South Korea and South Africa are all drawing US students more than ever before. This is partly because, I sense, the quality of qualifications is achieving parity across the globe; and also, because students who are prepared to travel realise that cultural specificity – the ability to learn new and unique aspects of a different culture while gaining the same core ingredients of a degree – sets it apart from the degree gained locally. A one semester course in Russian anthropology might appear entirely redundant when applying for a job. However, the very interconnectedness of global business means not only that the course is never a waste of time, but that it might mean the difference between landing a contract and failing to do so. The international student has the benefit of developing in ways that traditional (home-grown) higher education may not yet fully understand. Secondly, development in South Africa at least, has an additional meaning. Our universities are not only focused on developing graduates for multicultural or global competitiveness. Over the past five or so years our universities have been focused on development of the country itself. As an emerging power, the impetus has been on creating universities that address the fundamental needs of the people. Poverty, HIV, sustainability and innovative solutions to global problems are the very sap of South African universities in the 21st Century. How to create a sustainable environment, how to preserve marine and wildlife, how to create jobs, reduce poverty, and maximise innovation – these are the concerns that are preoccupying the minds of the country’s best academics. , 11th Edition
- Full Text:
- Date Issued: 2011
- Authors: International Education Association of South Africa (IEASA) , Jooste, Nico
- Date: 2011
- Subjects: Education, Higher -- South Africa , Universities and colleges -- South Africa , Technical Institutes -- South Africa , Vocational guidance -- South Africa
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/64952 , vital:28639 , ISBN 9780620512244
- Description: [Extract from article by Ms Merle Hodges]: Over the past year there have been numerous conferences dealing with one general topic. How is it possible for higher education, globally, to produce the same quality in its graduates, research and community outreach when the financial resources entering into the system are radically declining? The conclusion is overwhelmingly despondent. ‘Universities have to do more with less, academics and academic research will increasingly be pressurised by lower salaries internally and career temptations from the corporate world – the impact of which is the greater commodification of universities, and the inevitable decline in academic freedom.’ This global negativity is predicated on inter–related factors. The first, the long tail of the economic recession, is continuing to bite all sectors and higher education is no exception. Secondly, higher education is a little like marketing – when the pressure is on government, sectors like higher education are de–prioritised. In light of this, the position of internationalisation in higher education might seem to fade into the background. Interestingly, the inverse is true. While the zeitgeist of higher education generally appears dismal, the prospects of internationalisation appear rosy in comparison. I believe this is true because of two overlapping issues. Firstly, students are not going to give up on university because of a lingering economic downturn. What they are doing, however, is deciding to travel and study at destinations that would have been perceived as implausible a few years ago. Venezuela, Chile, South Korea and South Africa are all drawing US students more than ever before. This is partly because, I sense, the quality of qualifications is achieving parity across the globe; and also, because students who are prepared to travel realise that cultural specificity – the ability to learn new and unique aspects of a different culture while gaining the same core ingredients of a degree – sets it apart from the degree gained locally. A one semester course in Russian anthropology might appear entirely redundant when applying for a job. However, the very interconnectedness of global business means not only that the course is never a waste of time, but that it might mean the difference between landing a contract and failing to do so. The international student has the benefit of developing in ways that traditional (home-grown) higher education may not yet fully understand. Secondly, development in South Africa at least, has an additional meaning. Our universities are not only focused on developing graduates for multicultural or global competitiveness. Over the past five or so years our universities have been focused on development of the country itself. As an emerging power, the impetus has been on creating universities that address the fundamental needs of the people. Poverty, HIV, sustainability and innovative solutions to global problems are the very sap of South African universities in the 21st Century. How to create a sustainable environment, how to preserve marine and wildlife, how to create jobs, reduce poverty, and maximise innovation – these are the concerns that are preoccupying the minds of the country’s best academics. , 11th Edition
- Full Text:
- Date Issued: 2011
Surface properties and electrocatalytic applications of metallophthalocyanines confined on electrode surfaces
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
Survival analysis of SMMEs in Botswana
- Authors: Mannathoko, Bame Joshua
- Date: 2011
- Subjects: Small business -- Botswana , Sex discrimination against women -- Botswana , Finance -- Botswana
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:8984 , http://hdl.handle.net/10948/1531 , Small business -- Botswana , Sex discrimination against women -- Botswana , Finance -- Botswana
- Description: This study investigates the factors influencing survival of micro enterprises funded by the Department of Youth in Botswana. Data drawn from 271 business ventures established between the years 2005 and 2009 was analysed by using the Cox proportional hazards model (CPHM), a survival analysis technique. Results from the analysis suggest that businesses operated by younger owners endure a higher risk of failure in comparison to businesses owned by older entrepreneurs while firm size at start-up was also a significant determinant of survival. As a component of human capital, a personal contribution to the start-up capital and prior employment experience were also found to be significant predictors of business survival. Regarding gender of the business owner, the claim that female operated businesses face a higher probability of failure when compared to businesses run by males was not supported by the study results. The amount of funding from the DOY at start-up was found not to have any influence on the survival or failure outcomes for the business projects. Based on these findings, certain policy implications can be deduced. This study recommends that policy makers focus more on human capital requirements of beneficiaries of government business development initiatives as well as entrepreneur contribution to start-up capital in order to increase the success rate of the business ventures. In addition, the capacity to perform continuous monitoring and mentoring of government funded businesses ventures, particularly SMMEs, should be increased within the relevant departments or alternatively outsourcing of the requisite skills should be considered. Lastly, recommendation to replicate this research, at a larger scale in future is proposed.
- Full Text:
- Date Issued: 2011
- Authors: Mannathoko, Bame Joshua
- Date: 2011
- Subjects: Small business -- Botswana , Sex discrimination against women -- Botswana , Finance -- Botswana
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: vital:8984 , http://hdl.handle.net/10948/1531 , Small business -- Botswana , Sex discrimination against women -- Botswana , Finance -- Botswana
- Description: This study investigates the factors influencing survival of micro enterprises funded by the Department of Youth in Botswana. Data drawn from 271 business ventures established between the years 2005 and 2009 was analysed by using the Cox proportional hazards model (CPHM), a survival analysis technique. Results from the analysis suggest that businesses operated by younger owners endure a higher risk of failure in comparison to businesses owned by older entrepreneurs while firm size at start-up was also a significant determinant of survival. As a component of human capital, a personal contribution to the start-up capital and prior employment experience were also found to be significant predictors of business survival. Regarding gender of the business owner, the claim that female operated businesses face a higher probability of failure when compared to businesses run by males was not supported by the study results. The amount of funding from the DOY at start-up was found not to have any influence on the survival or failure outcomes for the business projects. Based on these findings, certain policy implications can be deduced. This study recommends that policy makers focus more on human capital requirements of beneficiaries of government business development initiatives as well as entrepreneur contribution to start-up capital in order to increase the success rate of the business ventures. In addition, the capacity to perform continuous monitoring and mentoring of government funded businesses ventures, particularly SMMEs, should be increased within the relevant departments or alternatively outsourcing of the requisite skills should be considered. Lastly, recommendation to replicate this research, at a larger scale in future is proposed.
- Full Text:
- Date Issued: 2011
Syntheses and electrochemical characterization of new water soluble octaarylthiosubstituted manganese phthalocyanines
- Booysen, Irvin N, Matemadombo, Fungisai, Durmus, Mahmut, Nyokong, Tebello
- Authors: Booysen, Irvin N , Matemadombo, Fungisai , Durmus, Mahmut , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247614 , vital:51600 , xlink:href="https://doi.org/10.1016/j.dyepig.2010.09.012"
- Description: This paper reports on the synthesis and characterization of new manganese phthalocyanine (MnPc) complexes: 2,3-octakis-[(2-mercaptopyridine) phthalocyaninato] acetato manganese (III) (1) and its quaternized (hence water soluble) derivative: 2,3-octakis-{[(N-methyl-2-mercaptopyridine) phthalocyaninato] acetato manganese (III)} sulphate (2). The complexes were used to form self assembled monolayers (SAMs). Voltammetry proved that both of the SAMs are well packed, strongly passivating and act as selective and efficient barriers to ion permeability. Furthermore, surface coverage studies confirmed that the MPc macrocycles adsorb onto the gold electrode as monolayers. Both MPc SAMs were successfully used as electrochemical sensors of nitrite.
- Full Text:
- Date Issued: 2011
- Authors: Booysen, Irvin N , Matemadombo, Fungisai , Durmus, Mahmut , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247614 , vital:51600 , xlink:href="https://doi.org/10.1016/j.dyepig.2010.09.012"
- Description: This paper reports on the synthesis and characterization of new manganese phthalocyanine (MnPc) complexes: 2,3-octakis-[(2-mercaptopyridine) phthalocyaninato] acetato manganese (III) (1) and its quaternized (hence water soluble) derivative: 2,3-octakis-{[(N-methyl-2-mercaptopyridine) phthalocyaninato] acetato manganese (III)} sulphate (2). The complexes were used to form self assembled monolayers (SAMs). Voltammetry proved that both of the SAMs are well packed, strongly passivating and act as selective and efficient barriers to ion permeability. Furthermore, surface coverage studies confirmed that the MPc macrocycles adsorb onto the gold electrode as monolayers. Both MPc SAMs were successfully used as electrochemical sensors of nitrite.
- Full Text:
- Date Issued: 2011
Syntheses, electrochemical and spectroelectrochemical properties of novel ball-type and mononuclear Co (II) phthalocyanines substituted at the peripheral and non-peripheral positions with binaphthol groups
- Canlıca, Mevlüde, Booysen, Irvin Noel, Nyokong, Tebello
- Authors: Canlıca, Mevlüde , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247837 , vital:51622 , xlink:href="https://doi.org/10.1016/j.poly.2010.11.017"
- Description: Mononuclear cobalt phthalocyanine (CoPc) substituted at the non-peripheral 8 and peripheral positions 9 with 1,1′-binaphthyl-8,8′-diol and ball-type dinuclear Co2Pc2 substituted at the non-peripheral 10 and peripheral 11 positions with the same substituent are reported. The complexes with 1,1′-binaphthol-bridges were prepared from the corresponding phthalonitriles 4–7. The effects of the position of substituent on spectral, electrochemical and spectroelectrochemical properties of these complexes were also explored. The mononuclear complexes 8 and 9 exhibited one metal reduction, one ring reduction and one ring oxidation. The redox properties of the ball-type complexes 10 and 11 exhibited two reduction processes assigned to [(CoIPc−2)2]2−/[(CoIPc−3)2]4− (I), (CoIIPc−2)2/[(CoIPc−2)2]2− (II) and one oxidation process assigned to [(CoIIIPc−2)2]2+/CoIIPc−2)2 (III). The ball-type complexes are much easier to oxidize and more difficult to reduce than the corresponding monomers 8 and 9.
- Full Text:
- Date Issued: 2011
- Authors: Canlıca, Mevlüde , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247837 , vital:51622 , xlink:href="https://doi.org/10.1016/j.poly.2010.11.017"
- Description: Mononuclear cobalt phthalocyanine (CoPc) substituted at the non-peripheral 8 and peripheral positions 9 with 1,1′-binaphthyl-8,8′-diol and ball-type dinuclear Co2Pc2 substituted at the non-peripheral 10 and peripheral 11 positions with the same substituent are reported. The complexes with 1,1′-binaphthol-bridges were prepared from the corresponding phthalonitriles 4–7. The effects of the position of substituent on spectral, electrochemical and spectroelectrochemical properties of these complexes were also explored. The mononuclear complexes 8 and 9 exhibited one metal reduction, one ring reduction and one ring oxidation. The redox properties of the ball-type complexes 10 and 11 exhibited two reduction processes assigned to [(CoIPc−2)2]2−/[(CoIPc−3)2]4− (I), (CoIIPc−2)2/[(CoIPc−2)2]2− (II) and one oxidation process assigned to [(CoIIIPc−2)2]2+/CoIIPc−2)2 (III). The ball-type complexes are much easier to oxidize and more difficult to reduce than the corresponding monomers 8 and 9.
- Full Text:
- Date Issued: 2011
Synthesis and electrocatalytic behavior of cobalt (II)-tris (benzyl-mercapto)-monoaminophthalocyanine–single walled carbon nanotube nanorods
- Mugadza, Tawanda, Nyokong, Tebello
- Authors: Mugadza, Tawanda , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247882 , vital:51626 , xlink:href="https://doi.org/10.1016/j.electacta.2010.11.016"
- Description: In this paper we report on synthesis and electrocatalytic behavior of cobalt (II)-tris(benzyl-mercapto)-monoaminophthalocyanine–single walled carbon nanotube nanorods towards the oxidation of amitrole. SWCNTs that were terminally functionalized with carboxylic acid groups were chemically linked to cobalt (II)-tris(benzyl-mercapto) monoaminophthalocyanine (CoMAPc) via an amide bond to form nanorods. UV–vis, FTIR, TEM, Raman and XRD spectroscopies were used in characterization of the nanorods (CoMAPc–SWCNT-linked), while cyclic voltammetry and chronoamperometry were used during the characterization of amitrole on the modified glassy carbon electrode. The linear dynamic range for the amitrole was from 1.0 × 10−6 M to 1.2 × 10−4 M, with a sensitivity of 6.76 A mol−1 L cm−2. The estimated limit of detection for amitrole was 0.10 μM, using the 3δ criterion. The catalytic rate constant was found to be 1.09 × 105 M−1 s−1.
- Full Text:
- Date Issued: 2011
- Authors: Mugadza, Tawanda , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247882 , vital:51626 , xlink:href="https://doi.org/10.1016/j.electacta.2010.11.016"
- Description: In this paper we report on synthesis and electrocatalytic behavior of cobalt (II)-tris(benzyl-mercapto)-monoaminophthalocyanine–single walled carbon nanotube nanorods towards the oxidation of amitrole. SWCNTs that were terminally functionalized with carboxylic acid groups were chemically linked to cobalt (II)-tris(benzyl-mercapto) monoaminophthalocyanine (CoMAPc) via an amide bond to form nanorods. UV–vis, FTIR, TEM, Raman and XRD spectroscopies were used in characterization of the nanorods (CoMAPc–SWCNT-linked), while cyclic voltammetry and chronoamperometry were used during the characterization of amitrole on the modified glassy carbon electrode. The linear dynamic range for the amitrole was from 1.0 × 10−6 M to 1.2 × 10−4 M, with a sensitivity of 6.76 A mol−1 L cm−2. The estimated limit of detection for amitrole was 0.10 μM, using the 3δ criterion. The catalytic rate constant was found to be 1.09 × 105 M−1 s−1.
- Full Text:
- Date Issued: 2011
Synthesis and electrochemical behavior of novel peripherally and non-peripherally substituted ball-type cobalt phthalocyanine complexes
- Canlıca, Mevlüde, Booysen, Irvin Noel, Nyokong, Tebello
- Authors: Canlıca, Mevlüde , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247848 , vital:51623 , xlink:href="https://doi.org/10.1016/j.poly.2010.11.028"
- Description: The syntheses of new ball-type Co(II) phthalocyanines containing 4,4′-(9H-fluorene-9,9-diyl)diphenol substituents at non-peripheral (complex 6) and peripheral (complex 7) positions are presented. These complexes were characterized by UV–Vis, FT-IR, mass spectroscopy and electrochemical methods. Both complexes exhibit metal and ring based redox processes, typical of cobalt phthalocyanine complexes. For 6, the metal based reduction was observed at −0.46 V followed by a ring based reduction at −1.40 V. The metal oxidation for 6 was observed at +0.16 V and the ring based oxidation at +1.05 V. For 7, reductions are easier but the oxidations are more difficult. The metal based reduction for 7 was observed at −0.38 V followed by a ring based reduction at −1.03 V. The metal oxidation for 7 was observed at +0.20 V and the ring based oxidation at +1.35 V.
- Full Text:
- Date Issued: 2011
- Authors: Canlıca, Mevlüde , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247848 , vital:51623 , xlink:href="https://doi.org/10.1016/j.poly.2010.11.028"
- Description: The syntheses of new ball-type Co(II) phthalocyanines containing 4,4′-(9H-fluorene-9,9-diyl)diphenol substituents at non-peripheral (complex 6) and peripheral (complex 7) positions are presented. These complexes were characterized by UV–Vis, FT-IR, mass spectroscopy and electrochemical methods. Both complexes exhibit metal and ring based redox processes, typical of cobalt phthalocyanine complexes. For 6, the metal based reduction was observed at −0.46 V followed by a ring based reduction at −1.40 V. The metal oxidation for 6 was observed at +0.16 V and the ring based oxidation at +1.05 V. For 7, reductions are easier but the oxidations are more difficult. The metal based reduction for 7 was observed at −0.38 V followed by a ring based reduction at −1.03 V. The metal oxidation for 7 was observed at +0.20 V and the ring based oxidation at +1.35 V.
- Full Text:
- Date Issued: 2011
Synthesis and electrochemical properties of new tetra substituted cobalt phthalocyanine complexes, and their application in electrode modification for the electrocatalysis of l-cysteine
- Erdoğmuş, Ali, Booysen, Irvin Noel, Nyokong, Tebello
- Authors: Erdoğmuş, Ali , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247893 , vital:51627 , xlink:href="https://doi.org/10.1016/j.synthmet.2010.11.028"
- Description: This study investigates the synthesis and characterization new peripherally (β) tetra-substituted 4-(2-mercaptoquinoline phthalocyaninato) Co(II) (CoPcSHQn, 3), and 4-(2-phenoxy-4-trifluoromethylpyridine phthalocyaninato) Co(II) (CoPcOHPy, 4). These complexes were characterized by elemental analysis, IR, mass and electronic spectroscopies and electrochemical methods. Both complexes show well resolved redox peaks attributed to both ring and metal based processes. Spectroelectrochemistry was used to confirm the assignments of the redox processes. For CoPcSHQn (3): CoIPc−2/CoIPc−3 (E1/2 = −1.25 V, I), CoIIPc−2/CoIPc−2 (E1/2 = −0.57 V, II), CoIIIPc−2/CoIIPc−2 (E1/2 = +0.45 V, IV) and an irreversible process at Ep = +1.05 V vs Ag|AgCl for CoIIIPc−1/CoIIIPc−2 (V). Redox couple III at E1/2 = −0.15 V was ascribed to aggregation. In the case of CoPcOHPy (4): CoIPc−2/CoIPc−3 (E1/2 = −1.13 V, I), CoIIPc−2/CoIPc−2 (E1/2 = −0.45 V, II), CoIIIPc−2/CoIIPc−2 at E1/2 = +0.21 V (IV), and CoIIIPc−1/CoIIIPc−2 (E1/2 = +1.01 V vs Ag|AgCl, V). Again III is associated with the aggregated species. Both complexes were electrodeposited on a glassy carbon electrode (GCE). For complex 3 self-assembled monolayers was also formed. The modified (CoPc-GCE) electrodes electrocatalytically detected L-cysteine at Ep = 0.62 V (3-GCE) and 0.59 V (4-GCE) vs Ag|AgCl.
- Full Text:
- Date Issued: 2011
- Authors: Erdoğmuş, Ali , Booysen, Irvin Noel , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247893 , vital:51627 , xlink:href="https://doi.org/10.1016/j.synthmet.2010.11.028"
- Description: This study investigates the synthesis and characterization new peripherally (β) tetra-substituted 4-(2-mercaptoquinoline phthalocyaninato) Co(II) (CoPcSHQn, 3), and 4-(2-phenoxy-4-trifluoromethylpyridine phthalocyaninato) Co(II) (CoPcOHPy, 4). These complexes were characterized by elemental analysis, IR, mass and electronic spectroscopies and electrochemical methods. Both complexes show well resolved redox peaks attributed to both ring and metal based processes. Spectroelectrochemistry was used to confirm the assignments of the redox processes. For CoPcSHQn (3): CoIPc−2/CoIPc−3 (E1/2 = −1.25 V, I), CoIIPc−2/CoIPc−2 (E1/2 = −0.57 V, II), CoIIIPc−2/CoIIPc−2 (E1/2 = +0.45 V, IV) and an irreversible process at Ep = +1.05 V vs Ag|AgCl for CoIIIPc−1/CoIIIPc−2 (V). Redox couple III at E1/2 = −0.15 V was ascribed to aggregation. In the case of CoPcOHPy (4): CoIPc−2/CoIPc−3 (E1/2 = −1.13 V, I), CoIIPc−2/CoIPc−2 (E1/2 = −0.45 V, II), CoIIIPc−2/CoIIPc−2 at E1/2 = +0.21 V (IV), and CoIIIPc−1/CoIIIPc−2 (E1/2 = +1.01 V vs Ag|AgCl, V). Again III is associated with the aggregated species. Both complexes were electrodeposited on a glassy carbon electrode (GCE). For complex 3 self-assembled monolayers was also formed. The modified (CoPc-GCE) electrodes electrocatalytically detected L-cysteine at Ep = 0.62 V (3-GCE) and 0.59 V (4-GCE) vs Ag|AgCl.
- Full Text:
- Date Issued: 2011
Synthesis and evaluation of novel HIV-1 enzyme inhibitors
- Olomola, Temitope Oloruntoba
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
Synthesis and evaluation of phosphonated N-heteroarylcarboxamides as DOXP-reductoisomerase (DXR) inhibitors
- Bodill, Taryn, Conibear, Anne C, Blatch, Gregory L, Lobb, Kevin A, Kaye, Perry T
- Authors: Bodill, Taryn , Conibear, Anne C , Blatch, Gregory L , Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448939 , vital:74772 , xlink:href="https://doi.org/10.1016/j.bmc.2010.11.062"
- Description: The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design.
- Full Text:
- Date Issued: 2011
- Authors: Bodill, Taryn , Conibear, Anne C , Blatch, Gregory L , Lobb, Kevin A , Kaye, Perry T
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448939 , vital:74772 , xlink:href="https://doi.org/10.1016/j.bmc.2010.11.062"
- Description: The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design.
- Full Text:
- Date Issued: 2011
Synthesis and photophysical behaviour of tantalum and titanium phthalocyanines in the presence of gold nanoparticles
- Chauke, Vongani P, Arslanoglu, Yasin, Nyokong, Tebello
- Authors: Chauke, Vongani P , Arslanoglu, Yasin , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247545 , vital:51593 , xlink:href="https://doi.org/10.1016/j.jphotochem.2011.04.020"
- Description: We report on the synthesis of 2,(3)- (peripheral) and 1,(4)- (non-peripheral) (2-mercaptopyridine)phthalocyanine complexes of titanium (IV) oxide (5 and 6 respectively), and tantalum (III) hydroxide (7, peripheral only), their photochemical and photophysical parameters and the photocatalytic oxidation of cyclohexene in the presence of gold nanoparticles (AuNPs). The singlet oxygen quantum yield values increased in the presence of AuNPs, for complexes 5 and 6. The percentage conversion values for cyclohexene using 5, 6 and 7 were 27%, 20% and 14%, respectively. These values increased considerably in the presence of AuNPs, except complex for 7. The products obtained include cyclohexene oxide, 2-cyclohexen-1-ol, 2-cyclohexene-1-one and 1,2-cyclohexanediol. Low values of singlet oxygen quantum yields favour the formation of 1,2-cyclohexanediol.
- Full Text:
- Date Issued: 2011
- Authors: Chauke, Vongani P , Arslanoglu, Yasin , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247545 , vital:51593 , xlink:href="https://doi.org/10.1016/j.jphotochem.2011.04.020"
- Description: We report on the synthesis of 2,(3)- (peripheral) and 1,(4)- (non-peripheral) (2-mercaptopyridine)phthalocyanine complexes of titanium (IV) oxide (5 and 6 respectively), and tantalum (III) hydroxide (7, peripheral only), their photochemical and photophysical parameters and the photocatalytic oxidation of cyclohexene in the presence of gold nanoparticles (AuNPs). The singlet oxygen quantum yield values increased in the presence of AuNPs, for complexes 5 and 6. The percentage conversion values for cyclohexene using 5, 6 and 7 were 27%, 20% and 14%, respectively. These values increased considerably in the presence of AuNPs, except complex for 7. The products obtained include cyclohexene oxide, 2-cyclohexen-1-ol, 2-cyclohexene-1-one and 1,2-cyclohexanediol. Low values of singlet oxygen quantum yields favour the formation of 1,2-cyclohexanediol.
- Full Text:
- Date Issued: 2011
Synthesis and photophysical properties of a novel zinc photosensitizer and its gold nanoparticle conjugate
- Moeno, Sharon, Antunes, Edith M, Nyokong, Tebello
- Authors: Moeno, Sharon , Antunes, Edith M , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247100 , vital:51546 , xlink:href="https://doi.org/10.1016/j.jphotochem.2011.07.007"
- Description: The peripherally tetra substituted zinc phthalocyanine with 1,6-hexanedithiol as substituent (THdTZnPc, 3) was synthesized and is reported for the first time in this work. The potential of this zinc complex as a suitable photosensitizer for use in photodynamic therapy was determined through the investigation of the photophysical and photochemical properties. In this work complex 3 is attached to gold nanoparticles through the terminal thiol groups of the phthalocyanine resulting in a 3-AuNP conjugate whose photophysicochemical properties are investigated. Fluorescence lifetimes were determined using time correlated single photon counting and they show an increase in the abundance of the monomeric species (τ2) for the Pc in the 3-AuNP conjugate: ∼1 and 0.71 (with respective lifetimes 2.69 ns and 2.86 ns) compared to the free complex 3 with abundances of 0.12 and 0.13 (with respective lifetimes 3.36 ns and 3.28 ns) in DMSO and DMF, respectively.
- Full Text:
- Date Issued: 2011
- Authors: Moeno, Sharon , Antunes, Edith M , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247100 , vital:51546 , xlink:href="https://doi.org/10.1016/j.jphotochem.2011.07.007"
- Description: The peripherally tetra substituted zinc phthalocyanine with 1,6-hexanedithiol as substituent (THdTZnPc, 3) was synthesized and is reported for the first time in this work. The potential of this zinc complex as a suitable photosensitizer for use in photodynamic therapy was determined through the investigation of the photophysical and photochemical properties. In this work complex 3 is attached to gold nanoparticles through the terminal thiol groups of the phthalocyanine resulting in a 3-AuNP conjugate whose photophysicochemical properties are investigated. Fluorescence lifetimes were determined using time correlated single photon counting and they show an increase in the abundance of the monomeric species (τ2) for the Pc in the 3-AuNP conjugate: ∼1 and 0.71 (with respective lifetimes 2.69 ns and 2.86 ns) compared to the free complex 3 with abundances of 0.12 and 0.13 (with respective lifetimes 3.36 ns and 3.28 ns) in DMSO and DMF, respectively.
- Full Text:
- Date Issued: 2011
Synthesis and photophysical studies of CdTe quantum dot-monosubstituted zinc phthalocyanine conjugates
- D'Souza, Sarah, Antunes, Edith M, Nyokong, Tebello
- Authors: D'Souza, Sarah , Antunes, Edith M , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247825 , vital:51621 , xlink:href="https://doi.org/10.1016/j.ica.2010.12.027"
- Description: The linkage of unsymmetrically monosubstituted 4-aminophenoxy zinc phthalocyanine (ZnAPPc, 5) to CdTe quantum dots capped with mercaptopropionic acid (MPA), L-cysteine (L-cys) or thioglycolic acid (TGA) has been achieved using the coupling agents ethyl-N(3-dimethylaminopropyl) carbodiimide and N-hydroxy succinimide, which facilitate formation of an amide bond to form the QD–ZnAPPc-linked conjugate. The formation of the amide bond was confirmed using Raman and IR spectroscopies. Atomic force microscopy (AFM) and UV–Vis spectroscopy were used further to characterise the conjugate. Förster resonance energy transfer (FRET) resulted in stimulated emission of ZnAPPc in both the linked (QD–ZnAPPc-linked) and mixed (QD:ZnAPPc-mixed) conjugates. The linked L-cys and TGA QDs conjugates (QD–ZnAPPc-linked) gave the largest FRET efficiencies hence showing the advantages of covalent linking. Fluorescence quantum yields of QDs were decreased in QD:ZnAPPc-mixed and QD:ZnAPPc-linked.
- Full Text:
- Date Issued: 2011
- Authors: D'Souza, Sarah , Antunes, Edith M , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/247825 , vital:51621 , xlink:href="https://doi.org/10.1016/j.ica.2010.12.027"
- Description: The linkage of unsymmetrically monosubstituted 4-aminophenoxy zinc phthalocyanine (ZnAPPc, 5) to CdTe quantum dots capped with mercaptopropionic acid (MPA), L-cysteine (L-cys) or thioglycolic acid (TGA) has been achieved using the coupling agents ethyl-N(3-dimethylaminopropyl) carbodiimide and N-hydroxy succinimide, which facilitate formation of an amide bond to form the QD–ZnAPPc-linked conjugate. The formation of the amide bond was confirmed using Raman and IR spectroscopies. Atomic force microscopy (AFM) and UV–Vis spectroscopy were used further to characterise the conjugate. Förster resonance energy transfer (FRET) resulted in stimulated emission of ZnAPPc in both the linked (QD–ZnAPPc-linked) and mixed (QD:ZnAPPc-mixed) conjugates. The linked L-cys and TGA QDs conjugates (QD–ZnAPPc-linked) gave the largest FRET efficiencies hence showing the advantages of covalent linking. Fluorescence quantum yields of QDs were decreased in QD:ZnAPPc-mixed and QD:ZnAPPc-linked.
- Full Text:
- Date Issued: 2011
Synthesis and photophysical studies of monocarboxy phthalocyanines containing quaternizable groups
- Arslanoğlu, Yasin, Nyokong, Tebello
- Authors: Arslanoğlu, Yasin , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/246992 , vital:51535 , xlink:href="https://doi.org/10.1016/j.poly.2011.08.009"
- Description: This work reports on the synthesis and photophysical properties of novel unsymmetrically substituted monocarboxy magnesium (MgPc, 3), aluminum (ClAlPc, 4) and unmetallated (H2Pc, 5) phthalocyanines. Magnesium phthalocyanine (3) was converted into water soluble quaternized derivative (QMgPc, 6) by reaction with methyl iodide. The synthesized phthalocyanines were characterized by IR, UV–Vis, NMR, mass spectrometry and elemental analyses. Photophysical and photochemical studies were carried out in order to determine the potential of the complexes as photosensitizers for use in photodynamic therapy. Triplet quantum yields ranged from 0.37 to 0.40 and triplet lifetimes from 110 to 140 μs in DMSO.
- Full Text:
- Date Issued: 2011
- Authors: Arslanoğlu, Yasin , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/246992 , vital:51535 , xlink:href="https://doi.org/10.1016/j.poly.2011.08.009"
- Description: This work reports on the synthesis and photophysical properties of novel unsymmetrically substituted monocarboxy magnesium (MgPc, 3), aluminum (ClAlPc, 4) and unmetallated (H2Pc, 5) phthalocyanines. Magnesium phthalocyanine (3) was converted into water soluble quaternized derivative (QMgPc, 6) by reaction with methyl iodide. The synthesized phthalocyanines were characterized by IR, UV–Vis, NMR, mass spectrometry and elemental analyses. Photophysical and photochemical studies were carried out in order to determine the potential of the complexes as photosensitizers for use in photodynamic therapy. Triplet quantum yields ranged from 0.37 to 0.40 and triplet lifetimes from 110 to 140 μs in DMSO.
- Full Text:
- Date Issued: 2011
Synthesis and photophysical studies of phthalocyanine–gold nanoparticle conjugates
- Nombona, Nolwazi, Antunes, Edith M, Litwinski, Christian, Nyokong, Tebello
- Authors: Nombona, Nolwazi , Antunes, Edith M , Litwinski, Christian , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/248438 , vital:51686 , xlink:href="https://doi.org/10.1039/C1DT11151E"
- Description: This work reports on the synthesis, characterization and photophysical studies of phthalocyanine–gold nanoparticle conjugates. The phthalocyanine complexes are: tris-(5-trifluoromethyl-2-mercaptopyridine)-2-(carboxy)phthalocyanine (3), 2,9,17,23-tetrakis-[(1, 6-hexanedithiol) phthalocyaninato]zinc(II) (8) and [8,15,22-tris-(naptho)-2(amidoethanethiol) phthalocyanato] zinc(II)(10). The gold nanoparticles were characterized using transmission electron microscopy, X-ray diffraction, atomic force microscopy and UV-vis spectroscopy where the size was confirmed to be ∼5 nm. The phthalocyanine Au nanoparticle conjugates showed lower fluorescence quantum yield values with similar fluorescence lifetimes compared to the free phthalocyanines. The Au nanoparticle conjugates of 3 and 10 also showed higher triplet quantum yields of 0.69 to 0.71, respectively. A lower triplet quantum yield was obtained for the conjugate compared to free phthalocyanine for complex 8. The triplet lifetimes ranged from 70 to 92 μs for the conjugates and from 110 to 304 μs for unbound Pc complexes.
- Full Text:
- Date Issued: 2011
- Authors: Nombona, Nolwazi , Antunes, Edith M , Litwinski, Christian , Nyokong, Tebello
- Date: 2011
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/248438 , vital:51686 , xlink:href="https://doi.org/10.1039/C1DT11151E"
- Description: This work reports on the synthesis, characterization and photophysical studies of phthalocyanine–gold nanoparticle conjugates. The phthalocyanine complexes are: tris-(5-trifluoromethyl-2-mercaptopyridine)-2-(carboxy)phthalocyanine (3), 2,9,17,23-tetrakis-[(1, 6-hexanedithiol) phthalocyaninato]zinc(II) (8) and [8,15,22-tris-(naptho)-2(amidoethanethiol) phthalocyanato] zinc(II)(10). The gold nanoparticles were characterized using transmission electron microscopy, X-ray diffraction, atomic force microscopy and UV-vis spectroscopy where the size was confirmed to be ∼5 nm. The phthalocyanine Au nanoparticle conjugates showed lower fluorescence quantum yield values with similar fluorescence lifetimes compared to the free phthalocyanines. The Au nanoparticle conjugates of 3 and 10 also showed higher triplet quantum yields of 0.69 to 0.71, respectively. A lower triplet quantum yield was obtained for the conjugate compared to free phthalocyanine for complex 8. The triplet lifetimes ranged from 70 to 92 μs for the conjugates and from 110 to 304 μs for unbound Pc complexes.
- Full Text:
- Date Issued: 2011
Synthesis of bromochloromethane using phase transfer catalysis
- Authors: Brooks, Lancelot L
- Date: 2011
- Subjects: Chemistry, Analytic , Fire extinguishing agents , Chemical systems , Physical science
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10382 , http://hdl.handle.net/10948/d1008162 , Chemistry, Analytic , Fire extinguishing agents , Chemical systems , Physical science
- Description: The synthesis of bromochloromethane (BCM) in a batch reactor, using phase transfer catalysis, was investigated. During the synthetic procedure, sodium bromide (100.0g, 0.97mol) along with an excess amount of dichloromethane (265.0g, 3.12 mol) was charged to a reactor containing benzyl triethylammonium chloride (13 mmol), dissolved in 50 ml of water. The bench scale reactions were all carried out in a Parr 4520 bench top pressure reactor coupled to a Parr 4841 temperature controller. The method produced a 50.0 percent yield of the product BCM after a reaction time of 12 to 13 hours. The main objective for this investigation was to optimize the abovementioned reaction with respect to yield and reactor throughput. Quantitative analysis of BCM was performed on a Focus Gas Chromatograph, fitted with a flame ionization detector, and a BP20 column (30m × 0,32mm ID × 0,25 mm). Delta software, version 5.0, was applied for data collection and processing. The injector and detector port were set at 250°C and 280°C, respectively. The oven temperature was set and held at 40°C for a period of 2 minutes, then gradually increased at a rate of 10°C/min to 130°C, with the final hold time set for 1 minute. An analytical method for the quantitative analysis of BCM was developed, optimized and validated. Validation of the analytical method commenced over a period of three days, and focussed the following validation parameters: Accuracy, precision, and ruggedness. Statistical evaluation of the results obtained for precision showed that the error between individual injections is less than 2 percent for each component. However, ANOVA analysis showed a significant difference between the mean response factors obtained in the three day period (p-value < 0.05). Thus we could conclude that the response factors had to be determined on each day before quantitatively analyzing samples. The accuracy of the analytical method was assessed by using the percent recovery method. Results obtained showed that a mean percent recovery of 100.18 percent was obtained for BCM, with the absolute bias = 0.0004, and the percent bias = 0.18 percent. Hence the 95 confidence intervals for the percent recovery and percent bias are given by: (Lz, Uz) = (100.56 percent percent 102.15 percent), 13 (LPB, UPB) = (0.56 percent, 2.15 percent), respectively. Since the 95 percent confidence interval for the percent recovery contains 100, or equivalently, the 95 percent confidence interval for percent bias contains 0, the assay method is considered accurate and validated for BCM. In the same manner the accuracy and percent recovery for DCM and DBM was evaluated. The method was found to be accurate and validated for DBM, however, slightly biased in determining the recovered amount of DCM. With the analytical method validated, the batch production process could be evaluated. A total of six process variables, namely reaction time, water amount, temperature, volume of the two phases, stirring rate, and catalyst concentration, were selected for the study. The effects of the individual variables were determined in the classical manner, by varying only the one of interest while keeping all others constant. The experimental data generated was fit to a quadratic response surface model. The profile plots that were obtained from this model allowed a visual representation of the effect of the six variables. The experimental results obtained showed that the reaction follows pseudo zero-order kinetics and that the rate of the reaction is directly proportional to the concentration of the catalyst. The reaction obeys the Arrhenius equation, and the relatively high activation energy of 87kJ.mol -1 signifies that the rate constant is strongly dependent on the temperature of the reaction. The results also showed that the formation of BCM is favoured by an increase in the reaction temperature, catalyst concentration, and a high organic: aqueous phase ratio. Thus the synthesis of BCM using phase transfer catalyst could be optimised, to obtain a 100 percent yield BCM, by increasing both the reaction temperature to 105°C, and the concentration of the phase transfer catalyst -benzyl triethylammonium chloride - to 5.36 mol percent. The reaction time was also reduced to 6 hours.
- Full Text:
- Date Issued: 2011
- Authors: Brooks, Lancelot L
- Date: 2011
- Subjects: Chemistry, Analytic , Fire extinguishing agents , Chemical systems , Physical science
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10382 , http://hdl.handle.net/10948/d1008162 , Chemistry, Analytic , Fire extinguishing agents , Chemical systems , Physical science
- Description: The synthesis of bromochloromethane (BCM) in a batch reactor, using phase transfer catalysis, was investigated. During the synthetic procedure, sodium bromide (100.0g, 0.97mol) along with an excess amount of dichloromethane (265.0g, 3.12 mol) was charged to a reactor containing benzyl triethylammonium chloride (13 mmol), dissolved in 50 ml of water. The bench scale reactions were all carried out in a Parr 4520 bench top pressure reactor coupled to a Parr 4841 temperature controller. The method produced a 50.0 percent yield of the product BCM after a reaction time of 12 to 13 hours. The main objective for this investigation was to optimize the abovementioned reaction with respect to yield and reactor throughput. Quantitative analysis of BCM was performed on a Focus Gas Chromatograph, fitted with a flame ionization detector, and a BP20 column (30m × 0,32mm ID × 0,25 mm). Delta software, version 5.0, was applied for data collection and processing. The injector and detector port were set at 250°C and 280°C, respectively. The oven temperature was set and held at 40°C for a period of 2 minutes, then gradually increased at a rate of 10°C/min to 130°C, with the final hold time set for 1 minute. An analytical method for the quantitative analysis of BCM was developed, optimized and validated. Validation of the analytical method commenced over a period of three days, and focussed the following validation parameters: Accuracy, precision, and ruggedness. Statistical evaluation of the results obtained for precision showed that the error between individual injections is less than 2 percent for each component. However, ANOVA analysis showed a significant difference between the mean response factors obtained in the three day period (p-value < 0.05). Thus we could conclude that the response factors had to be determined on each day before quantitatively analyzing samples. The accuracy of the analytical method was assessed by using the percent recovery method. Results obtained showed that a mean percent recovery of 100.18 percent was obtained for BCM, with the absolute bias = 0.0004, and the percent bias = 0.18 percent. Hence the 95 confidence intervals for the percent recovery and percent bias are given by: (Lz, Uz) = (100.56 percent percent 102.15 percent), 13 (LPB, UPB) = (0.56 percent, 2.15 percent), respectively. Since the 95 percent confidence interval for the percent recovery contains 100, or equivalently, the 95 percent confidence interval for percent bias contains 0, the assay method is considered accurate and validated for BCM. In the same manner the accuracy and percent recovery for DCM and DBM was evaluated. The method was found to be accurate and validated for DBM, however, slightly biased in determining the recovered amount of DCM. With the analytical method validated, the batch production process could be evaluated. A total of six process variables, namely reaction time, water amount, temperature, volume of the two phases, stirring rate, and catalyst concentration, were selected for the study. The effects of the individual variables were determined in the classical manner, by varying only the one of interest while keeping all others constant. The experimental data generated was fit to a quadratic response surface model. The profile plots that were obtained from this model allowed a visual representation of the effect of the six variables. The experimental results obtained showed that the reaction follows pseudo zero-order kinetics and that the rate of the reaction is directly proportional to the concentration of the catalyst. The reaction obeys the Arrhenius equation, and the relatively high activation energy of 87kJ.mol -1 signifies that the rate constant is strongly dependent on the temperature of the reaction. The results also showed that the formation of BCM is favoured by an increase in the reaction temperature, catalyst concentration, and a high organic: aqueous phase ratio. Thus the synthesis of BCM using phase transfer catalyst could be optimised, to obtain a 100 percent yield BCM, by increasing both the reaction temperature to 105°C, and the concentration of the phase transfer catalyst -benzyl triethylammonium chloride - to 5.36 mol percent. The reaction time was also reduced to 6 hours.
- Full Text:
- Date Issued: 2011
Synthesis of novel inhibitors of 1-Deoxy-D-xylulose-5-phosphate reductoisomerase as potential anti-malarial lead compounds
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011