Design and positioning of controls : the old and the new industrial approaches
- Authors: Dirkse van Schalkwyk, C J
- Date: 2001
- Language: English
- Type: Article
- Identifier: vital:6750 , http://hdl.handle.net/10962/d1009330
- Description: While copious amounts of research exist with regard to positioning of controls, very little research covers the design shape of the controls. This paper demonstrates the importance of control positioning and design within industrial settings. Furthermore it aims to highlight the changes in industries with regard to control design and positioning. This paper is a review paper and thus much is based on findings by other authors. However, the changes in the industrial practices referred to by the author are from knowledge gained while visiting numerous industries in South Africa.
- Full Text:
- Date Issued: 2001
- Authors: Dirkse van Schalkwyk, C J
- Date: 2001
- Language: English
- Type: Article
- Identifier: vital:6750 , http://hdl.handle.net/10962/d1009330
- Description: While copious amounts of research exist with regard to positioning of controls, very little research covers the design shape of the controls. This paper demonstrates the importance of control positioning and design within industrial settings. Furthermore it aims to highlight the changes in industries with regard to control design and positioning. This paper is a review paper and thus much is based on findings by other authors. However, the changes in the industrial practices referred to by the author are from knowledge gained while visiting numerous industries in South Africa.
- Full Text:
- Date Issued: 2001
Familiar claims : representations of same-gendered families in South African mainstream news media
- Authors: Morison, Tracy , Reddy, Vasu
- Date: 2013
- Language: English
- Type: Book chapter
- Identifier: vital:6211 , http://hdl.handle.net/10962/d1003062
- Description: From the Introduction: There has been significant reform of South African legislation pertaining to same-gendered families. The Constitution supports the rights of gay men and lesbians to establish life partnerships or, more recently, to enter into civil unions, to adopt children, keep custody of their own children in divorce proceedings, and to undertake co-parenting of their created families. Despite—or maybe because of—these developments, public debate on these issues is as lively and vociferous as it has ever been. At the time of writing this chapter, for instance, a veteran journalist published a column in a national newspaper in which he denounced same-gendered family “arrangements” as “neither the norm nor ultimately desirable” (Mulholland, 2013). Children in same-gendered families must be informed of this, he claimed. His argument was unsupported, save for unsubstantiated claims regarding the unnaturalness of same-gendered families, which defy “the natural order of things”, and the vehement refusal that “same-sex matrimony is the same as that of heterosexuals” (Mulholland, 2013). Mulholland’s column, which met with outrage by various activists and academics, demonstrates some of the ideas that circulate in public discussion of same-gendered families: concerns regarding the differences between homosexual and heterosexual families and the effects that these ‘differences’ might have on children living in ‘alternative’ families. In this chapter, we examine the public discussion, focusing on South African print media as a key site where debate has occurred. Recognising that the discussion of LGBTI issues in South Africa has increased in visibility over time, focusing on stories about coming out, rights, transgressions, stigma, discrimination and violence, this chapter concentrates on the public discussion in local print media that centre on ‘alternative’ family arrangements that are in contrast to a traditional heterosexual nuclear family. Drawing on a selection of print media reportage, we examine the social and public discourses that underpin and resist normative meanings associated with ‘the family’ as a social unit and, specifically, how same-gendered families (often rendered invisible and pathologised) are constructed within this material. , C. Lubbe & J. Marnell (Eds.) 2013. Home affairs: rethinking lesbian, gay, bisexual & transgender families in contemporary South Africa. A copy of the book can be obtained from: http://www.jacana.co.za
- Full Text:
- Date Issued: 2013
- Authors: Morison, Tracy , Reddy, Vasu
- Date: 2013
- Language: English
- Type: Book chapter
- Identifier: vital:6211 , http://hdl.handle.net/10962/d1003062
- Description: From the Introduction: There has been significant reform of South African legislation pertaining to same-gendered families. The Constitution supports the rights of gay men and lesbians to establish life partnerships or, more recently, to enter into civil unions, to adopt children, keep custody of their own children in divorce proceedings, and to undertake co-parenting of their created families. Despite—or maybe because of—these developments, public debate on these issues is as lively and vociferous as it has ever been. At the time of writing this chapter, for instance, a veteran journalist published a column in a national newspaper in which he denounced same-gendered family “arrangements” as “neither the norm nor ultimately desirable” (Mulholland, 2013). Children in same-gendered families must be informed of this, he claimed. His argument was unsupported, save for unsubstantiated claims regarding the unnaturalness of same-gendered families, which defy “the natural order of things”, and the vehement refusal that “same-sex matrimony is the same as that of heterosexuals” (Mulholland, 2013). Mulholland’s column, which met with outrage by various activists and academics, demonstrates some of the ideas that circulate in public discussion of same-gendered families: concerns regarding the differences between homosexual and heterosexual families and the effects that these ‘differences’ might have on children living in ‘alternative’ families. In this chapter, we examine the public discussion, focusing on South African print media as a key site where debate has occurred. Recognising that the discussion of LGBTI issues in South Africa has increased in visibility over time, focusing on stories about coming out, rights, transgressions, stigma, discrimination and violence, this chapter concentrates on the public discussion in local print media that centre on ‘alternative’ family arrangements that are in contrast to a traditional heterosexual nuclear family. Drawing on a selection of print media reportage, we examine the social and public discourses that underpin and resist normative meanings associated with ‘the family’ as a social unit and, specifically, how same-gendered families (often rendered invisible and pathologised) are constructed within this material. , C. Lubbe & J. Marnell (Eds.) 2013. Home affairs: rethinking lesbian, gay, bisexual & transgender families in contemporary South Africa. A copy of the book can be obtained from: http://www.jacana.co.za
- Full Text:
- Date Issued: 2013
Agreement and coordination in XiTsonga, SeSotho and IsiXhosa: an optimality theoretic perspective
- Authors: Mitchley, Hazel
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3423 , vital:20491
- Description: This thesis provides a unified Optimality Theoretic analysis of subject-verb agreement with coordinated preverbal subjects in three Southern Bantu languages: Xitsonga (S53), Sesotho (S33), and isiXhosa (S41). This analysis is then used to formulate a typology of agreement resolution strategies and the contexts which trigger them. Although some accounts in the Bantu literature suggest that agreement with coordinate structures is avoided by speakers (e.g. Schadeberg 1992, Voeltz 1971) especially when conjuncts are from different noun classes, I show that there is ample evidence to the contrary, and that the subject marker used is dependent on several factors, including (i) the [-HUMAN] specification on the conjuncts, (ii) whether the conjuncts are singular or plural, (iii) whether or not the conjuncts both carry the same noun class feature, and (iv) the order of the conjuncts. This thesis shows that there are various agreement resolution strategies which can beused: 1) agreement with the [+HUMAN] feature on the conjuncts, 2) agreement with the[-HUMAN] feature on the conjuncts, 3) agreement with the noun class feature on both conjuncts, 4) agreement with the noun class feature on the conjunct closest to the verb, and 5) agreement with the noun class feature on the conjunct furthest from the verb. Not all of these strategies are used by all languages, nor are these strategies interchangeable in the languages which do use them – instead, multiple factors conspire to trigger the use of a specific agreement strategy within a specific agreement featural context. I show that these effects can be captured using Optimality Theory (Prince and Smolensky 2004). The analysis makes use of seven constraints: RES#, MAX[+H], MAX[-H], DEP[-H], MAXNC, DEPNC, and AGREECLOSEST. The hierarchical ranking of these constraints not only accounts for the confinement of particular strategies to specific agreement featural contexts within a language, but also accounts for the cross-linguistic differences in the use of these strategies. I end off by examining the typological implications which follow from the OT analysis provided in this thesis.
- Full Text:
- Date Issued: 2016
- Authors: Mitchley, Hazel
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3423 , vital:20491
- Description: This thesis provides a unified Optimality Theoretic analysis of subject-verb agreement with coordinated preverbal subjects in three Southern Bantu languages: Xitsonga (S53), Sesotho (S33), and isiXhosa (S41). This analysis is then used to formulate a typology of agreement resolution strategies and the contexts which trigger them. Although some accounts in the Bantu literature suggest that agreement with coordinate structures is avoided by speakers (e.g. Schadeberg 1992, Voeltz 1971) especially when conjuncts are from different noun classes, I show that there is ample evidence to the contrary, and that the subject marker used is dependent on several factors, including (i) the [-HUMAN] specification on the conjuncts, (ii) whether the conjuncts are singular or plural, (iii) whether or not the conjuncts both carry the same noun class feature, and (iv) the order of the conjuncts. This thesis shows that there are various agreement resolution strategies which can beused: 1) agreement with the [+HUMAN] feature on the conjuncts, 2) agreement with the[-HUMAN] feature on the conjuncts, 3) agreement with the noun class feature on both conjuncts, 4) agreement with the noun class feature on the conjunct closest to the verb, and 5) agreement with the noun class feature on the conjunct furthest from the verb. Not all of these strategies are used by all languages, nor are these strategies interchangeable in the languages which do use them – instead, multiple factors conspire to trigger the use of a specific agreement strategy within a specific agreement featural context. I show that these effects can be captured using Optimality Theory (Prince and Smolensky 2004). The analysis makes use of seven constraints: RES#, MAX[+H], MAX[-H], DEP[-H], MAXNC, DEPNC, and AGREECLOSEST. The hierarchical ranking of these constraints not only accounts for the confinement of particular strategies to specific agreement featural contexts within a language, but also accounts for the cross-linguistic differences in the use of these strategies. I end off by examining the typological implications which follow from the OT analysis provided in this thesis.
- Full Text:
- Date Issued: 2016
Synthesis and characterisation of lanthanide complexes with nitrogen- and oxygen-donor ligands
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
Waste management in the pharmaceutical industry : an evaluation report of Dr Reddy's Laboratories
- Authors: Letsitsi, Ezekiel Tebogo
- Date: 2013
- Subjects: Pharmaceutical industry -- Waste disposal -- Case studies Hazardous wastes -- Management -- South Africa Hazardous wastes -- Management -- Law and legislation -- South Africa , Dr Reddy's Laboratories
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:718 , http://hdl.handle.net/10962/d1001872
- Description: The pharmaceutical industry must worry about managing pharmaceutical waste as it poses a health risk to human beings and its presence in the environment can also contribute to loss of biodiversity. Ngwuluka, Ochekpe, and Odumosu (2011: 11259) state that “Pharmaceuticals, though used to treat and manage diseases, are poisons, which justify the growing concerns about their presence in the environment.” Various forms of pharmaceutical waste exist, Ngwuluka et al. (2011) identified the following forms of pharmaceutical waste: Expired dosage forms, non-reworkable formulations, spilled pharmaceuticals, rejected active pharmaceutical ingredients, expired active pharmaceutical ingredients, and wastewater resulting from the water used for process operations during manufacturing and could come from the water used to clean equipment, pipes and floors, and would contain amongst other materials, chemicals and active pharmaceutical ingredients (APIs). A review on the pharmaceutical industry and the progress they have made in environmental management by generating health, safety and environmental programs, preventing pollution, waste minimization, recycling and reusing materials, investing in projects and facilities to ensure environmental sustainability have been established (Berry & Rondinelli, 2000). Dr. Reddy’s Laboratories is an Indian based pharmaceutical company which imports, markets and sells medicines in South Africa. Dr. Reddy’s has plans to set up a manufacturing plant in South Africa. The purpose of this study is to research waste management practices at Dr. Reddy’s plant in India and to draw parallels between India’s and South Africa’s waste legislation. This is to enable Dr. Reddy’s to review all aspects of its waste management systems, in order to revise where necessary and to improve the overall achievement of its waste management objectives in order to become a more sustainable organisation and to meet South African Waste legislation before setting up a plant in South Africa. 3 ii. Objective of the Evaluation Report The purpose of this research is to evaluate and analyse the development and implementation of a waste management system in a pharmaceutical company, specifically Dr. Reddy’s Laboratories. This is primarily to enable the company to review and analyse all aspects of waste management pertaining to pharmaceutical manufacturing and to revise or improve where necessary to ensure adherence to waste regulations as outlined by government. The following research goals have been also been identified: To identify and describe waste management practices at Dr. Reddy’s Laboratories, on the inherent assumption by the researcher that the company has a successful waste management strategy that would need to be reviewed to identify areas of improvement before expanding manufacturing facilities into South Africa. To evaluate, assess and compare similarities and/or differences between the identified South African Legislation for Waste Management with those identified during research conducted at Dr. Reddy’s iii. Importance of the Research Conducted Waste Management is important in that it not only removes from the environment, substances that can be harmful to humans and animals but it also enables an organisation to be more sustainable. According to Seadon (2010: i) “Integrated waste management is considered from a systems’ approach, with a particular emphasis on advancing sustainability”. The study will provide guidance to senior management, shop floor managers and employees who work in Dr. Reddy’s manufacturing plants as well as overall employees at Dr. Reddy’s on how to successfully implement a Waste Management programme to enhance sustainability at the organisation and realise the benefits to the organisation of being more sustainable. Weybrecht (2010) identified the following benefits that companies could gain by adopting sustainable waste management practices: reduced costs, resource preservation, keeping up with legislation, enhanced reputation, business differentiation from competitors, and attraction and retention of quality employees, and customer need satisfaction amongst many other benefits. This research needs to address the gap in analysing waste management practices (with more emphasis on waste treatment, waste minimisation, re-use, recycling and disposal), and implementation and understanding of waste management in the pharmaceutical industry as prior research was done mostly in other chemical industries and not to a large scale in the pharmaceutical industry. South African Waste Legislation, Indian Waste Legislation (as Dr. Reddy’s is based in India), as well as International Pharmaceutical Waste Management Guidelines, and International Pharmaceutical Good Manufacturing Practices provide a framework and benchmark of leading pharmaceutical waste management practices that can guide Dr. Reddy’s Laboratories’ leadership into integrating their waste management practices into their plans of setting up a manufacturing plant in South Africa. 5. Research Methodology This is evaluation research in the form of a case study and the data collection method employed is the conduction of a survey through questionnaires. The evaluation research also involves a document analysis of the organisation’s 2011 and 2012 annual reports, Dr. Reddy’s 2010 Sustainability Report as well as literature compiled by the organisation’s Corporate Communications Division. The research would also include review of existing literature on waste management. v. Structure of Dissertation This dissertation consists of three sections. Section 1: The Evaluation Report The section introduces the research area, provides the objectives of the research, provides contextual background information and describes the rationale for conducting the research. This section further describes Dr. Reddy’s waste management practice as outlined in relevant company documentation; it is also intended to highlight the specific waste management processes that were followed in the formulation and implementation of the waste management strategy. This section further describes the sample and presents the results of the survey, where the results are collated and reviewed in the context of the criteria set in the South African Waste Legislation, Indian Waste Legislation, as well as in International Pharmaceutical Waste Management Guidelines, and International Pharmaceutical Good Manufacturing Practices. The overall findings of this case study suggest that although management at Dr. Reddy’s are satisfied with waste management practices and results achieved at it manufacturing plant, there is however dissatisfaction amongst employees who believe the organisation has not successfully disseminated information and sufficiently trained them on waste management policies, processes and practices. There is therefore a desire amongst employees to be trained and to see the company improve on its waste management processes, this desire is a very important attribute as it indicates that employees at Dr. Reddy understand and are committed to the importance of waste management. Future research should be conducted to measure the legal impact of non-compliance to legislation governing waste management in the pharmaceutical company. Section 2: Literature Review The objective of the literature review is to provide a critical assessment and evaluation of previous research in the field of waste management in general as prior research was done mostly in other industries and not to a large scale in the pharmaceutical industry. The literature review evaluates the key elements of an effective waste management strategy implementation and is followed by a review of literature pertaining to the description of Pharmaceutical waste. Section 3: Research Methodology This section presents a description of how the work in this research was conducted. It presents the research process followed in compiling this case study, represented by the aims and objectives, research methodology and design, data collection techniques and data analysis.
- Full Text:
- Date Issued: 2013
- Authors: Letsitsi, Ezekiel Tebogo
- Date: 2013
- Subjects: Pharmaceutical industry -- Waste disposal -- Case studies Hazardous wastes -- Management -- South Africa Hazardous wastes -- Management -- Law and legislation -- South Africa , Dr Reddy's Laboratories
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: vital:718 , http://hdl.handle.net/10962/d1001872
- Description: The pharmaceutical industry must worry about managing pharmaceutical waste as it poses a health risk to human beings and its presence in the environment can also contribute to loss of biodiversity. Ngwuluka, Ochekpe, and Odumosu (2011: 11259) state that “Pharmaceuticals, though used to treat and manage diseases, are poisons, which justify the growing concerns about their presence in the environment.” Various forms of pharmaceutical waste exist, Ngwuluka et al. (2011) identified the following forms of pharmaceutical waste: Expired dosage forms, non-reworkable formulations, spilled pharmaceuticals, rejected active pharmaceutical ingredients, expired active pharmaceutical ingredients, and wastewater resulting from the water used for process operations during manufacturing and could come from the water used to clean equipment, pipes and floors, and would contain amongst other materials, chemicals and active pharmaceutical ingredients (APIs). A review on the pharmaceutical industry and the progress they have made in environmental management by generating health, safety and environmental programs, preventing pollution, waste minimization, recycling and reusing materials, investing in projects and facilities to ensure environmental sustainability have been established (Berry & Rondinelli, 2000). Dr. Reddy’s Laboratories is an Indian based pharmaceutical company which imports, markets and sells medicines in South Africa. Dr. Reddy’s has plans to set up a manufacturing plant in South Africa. The purpose of this study is to research waste management practices at Dr. Reddy’s plant in India and to draw parallels between India’s and South Africa’s waste legislation. This is to enable Dr. Reddy’s to review all aspects of its waste management systems, in order to revise where necessary and to improve the overall achievement of its waste management objectives in order to become a more sustainable organisation and to meet South African Waste legislation before setting up a plant in South Africa. 3 ii. Objective of the Evaluation Report The purpose of this research is to evaluate and analyse the development and implementation of a waste management system in a pharmaceutical company, specifically Dr. Reddy’s Laboratories. This is primarily to enable the company to review and analyse all aspects of waste management pertaining to pharmaceutical manufacturing and to revise or improve where necessary to ensure adherence to waste regulations as outlined by government. The following research goals have been also been identified: To identify and describe waste management practices at Dr. Reddy’s Laboratories, on the inherent assumption by the researcher that the company has a successful waste management strategy that would need to be reviewed to identify areas of improvement before expanding manufacturing facilities into South Africa. To evaluate, assess and compare similarities and/or differences between the identified South African Legislation for Waste Management with those identified during research conducted at Dr. Reddy’s iii. Importance of the Research Conducted Waste Management is important in that it not only removes from the environment, substances that can be harmful to humans and animals but it also enables an organisation to be more sustainable. According to Seadon (2010: i) “Integrated waste management is considered from a systems’ approach, with a particular emphasis on advancing sustainability”. The study will provide guidance to senior management, shop floor managers and employees who work in Dr. Reddy’s manufacturing plants as well as overall employees at Dr. Reddy’s on how to successfully implement a Waste Management programme to enhance sustainability at the organisation and realise the benefits to the organisation of being more sustainable. Weybrecht (2010) identified the following benefits that companies could gain by adopting sustainable waste management practices: reduced costs, resource preservation, keeping up with legislation, enhanced reputation, business differentiation from competitors, and attraction and retention of quality employees, and customer need satisfaction amongst many other benefits. This research needs to address the gap in analysing waste management practices (with more emphasis on waste treatment, waste minimisation, re-use, recycling and disposal), and implementation and understanding of waste management in the pharmaceutical industry as prior research was done mostly in other chemical industries and not to a large scale in the pharmaceutical industry. South African Waste Legislation, Indian Waste Legislation (as Dr. Reddy’s is based in India), as well as International Pharmaceutical Waste Management Guidelines, and International Pharmaceutical Good Manufacturing Practices provide a framework and benchmark of leading pharmaceutical waste management practices that can guide Dr. Reddy’s Laboratories’ leadership into integrating their waste management practices into their plans of setting up a manufacturing plant in South Africa. 5. Research Methodology This is evaluation research in the form of a case study and the data collection method employed is the conduction of a survey through questionnaires. The evaluation research also involves a document analysis of the organisation’s 2011 and 2012 annual reports, Dr. Reddy’s 2010 Sustainability Report as well as literature compiled by the organisation’s Corporate Communications Division. The research would also include review of existing literature on waste management. v. Structure of Dissertation This dissertation consists of three sections. Section 1: The Evaluation Report The section introduces the research area, provides the objectives of the research, provides contextual background information and describes the rationale for conducting the research. This section further describes Dr. Reddy’s waste management practice as outlined in relevant company documentation; it is also intended to highlight the specific waste management processes that were followed in the formulation and implementation of the waste management strategy. This section further describes the sample and presents the results of the survey, where the results are collated and reviewed in the context of the criteria set in the South African Waste Legislation, Indian Waste Legislation, as well as in International Pharmaceutical Waste Management Guidelines, and International Pharmaceutical Good Manufacturing Practices. The overall findings of this case study suggest that although management at Dr. Reddy’s are satisfied with waste management practices and results achieved at it manufacturing plant, there is however dissatisfaction amongst employees who believe the organisation has not successfully disseminated information and sufficiently trained them on waste management policies, processes and practices. There is therefore a desire amongst employees to be trained and to see the company improve on its waste management processes, this desire is a very important attribute as it indicates that employees at Dr. Reddy understand and are committed to the importance of waste management. Future research should be conducted to measure the legal impact of non-compliance to legislation governing waste management in the pharmaceutical company. Section 2: Literature Review The objective of the literature review is to provide a critical assessment and evaluation of previous research in the field of waste management in general as prior research was done mostly in other industries and not to a large scale in the pharmaceutical industry. The literature review evaluates the key elements of an effective waste management strategy implementation and is followed by a review of literature pertaining to the description of Pharmaceutical waste. Section 3: Research Methodology This section presents a description of how the work in this research was conducted. It presents the research process followed in compiling this case study, represented by the aims and objectives, research methodology and design, data collection techniques and data analysis.
- Full Text:
- Date Issued: 2013
Design, Optimization, Manufacture and Characterization of Efavirenz-Loaded Flaxseed Oil Nanoemulsions
- Mazonde, Priveledge, Khamanga, Sandile M, Walker, Roderick B
- Authors: Mazonde, Priveledge , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183183 , vital:43919 , xlink:href="https://doi.org/10.3390/pharmaceutics12090797"
- Description: The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
- Full Text:
- Date Issued: 2020
- Authors: Mazonde, Priveledge , Khamanga, Sandile M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183183 , vital:43919 , xlink:href="https://doi.org/10.3390/pharmaceutics12090797"
- Description: The formation, manufacture and characterization of low energy water-in-oil (w/o) nanoemulsions prepared using cold pressed flaxseed oil containing efavirenz was investigated. Pseudo-ternary phase diagrams were constructed to identify the nanoemulsion region(s). Other potential lipid-based drug delivery phases containing flaxseed oil with 1:1 m/m surfactant mixture of Tween® 80, Span® 20 and different amounts of ethanol were tested to characterize the impact of surfactant mixture on emulsion formation. Flaxseed oil was used as the oil phase as efavirenz exhibited high solubility in the vehicle when compared to other vegetable oils tested. Optimization of surfactant mixtures was undertaken using design of experiments, specifically a D-optimal design with the flaxseed oil content set at 10% m/m. Two solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, physical and chemical stability. Metastable nanoemulsions containing 10% m/m flaxseed oil were successfully manufactured and significant isotropic gel (semisolid) and o/w emulsions were observed during phase behavior studies. Droplet sizes ranged between 156 and 225 nm, zeta potential between −24 and −41 mV and all formulations were found to be monodisperse with polydispersity indices ≤ 0.487.
- Full Text:
- Date Issued: 2020
Benzoyl isothiocyanates derived ligands as potential HIV-1 protease inhibitors and their reactions with gold ions
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
Petrographic and geochemical characterisation of the hangingwall and the footwall rocks (the Dipeta and R.A.T. stratigraphic units) to the Kinsevere and Nambulwa copper ore deposits of the Lufilian Arc, southern Democratic Republic of Congo
- Authors: Nkulu, Robert Kankomba
- Date: 2020
- Subjects: Petrogenesis -- Congo (Democratic Republic) , Analytical geochemistry -- Congo (Democratic Republic) , Copper ores -- Congo (Democratic Republic) , Ore deposits -- Congo (Democratic Republic) , Katangan Sequence , Geological mapping -- Congo (Democratic Republic) , Central African Copperbelt (Congo and Zambia) , Lufilian Arc , Neoproterozoic Katangan R.A.T. (Roches Argilo Talqueuse) Subgroup , Dipeta Subgroup
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/142772 , vital:38115
- Description: The Kinsevere and Nambulwa copper deposits in the Democratic Republic of Congo (D.R.C.) are set in the eastern side of the Neoproterozoic Katanga Supergroup, forming the Lufilian Arc, resulting from a cratonic collision between the Congo and the Kalahari Cratons (ca.620-570_Ma). The Katanga Supergroup was deposited in an extensional rift setting with a sedimentary thickness succession ranging between 7 to 10 km, sub-divided into: − the Roan, the Nguba and the Kundelungu Groups. The stratigraphic column of the Roan Group consists of the R.A.T. (Roche Argilo Talqueuse), the Mines, the Dipeta and the Mwashya Subgroups. Three major deformation phases have been described characterised by complex multiphase tectonics related to a curved superposition of folded, thrust and sheared blocks. The rocks of the R.A.T., Mines and Dipeta Subgroups are recognised as blocks that occur within a stratiform to discordant and diapiritic megabreccia. The blocks were rafted upward with salt tectonics, resulting in the juxtaposition with the hangingwall and the footwall terranes. Therefore, in that context it has been found that the Dipeta may appear overlying the R.A.T. Subgroup through the unconformity decollement surface of heterogeneous breccia. The petrographic observations made of the R.A.T. and Dipeta samples indicates in both units the presence of detrital quartz and feldspar that have been altered and replaced by sericite and muscovite minerals. Gypsum is intimately associated with magnesite, showing an evaporitic environment domain, while magnesite is common as alteration phase both in the R.A.T. and Dipeta Subgroups. Pyrophyllite has been observed in the Dipeta, resulting from reaction of silica with the Kaolinite at low temperature. Accessory detrital minerals include zircon, as well as xenotime intergrown with altered Fe-Ti-oxide hematite, forming complex textures with disseminated Ti-oxides both in R.A.T. and Dipeta units. Major and trace element geochemistry indicates that the Dipeta is more dolomitic and magnesite while the R.A.T. is clay-rich. The Ti2O value of Dipeta and R.A.T samples is relatively low, ranging between 0.36 and 0.69 wt.% respectively, which suggest highly evolved felsic material in the protolith. This is consistent with interpretation based on the Al2O3/TiO2 ratio, which ranges between 18 and 23 for the R.A.T. and Dipeta respectively, indicating an intermediate to felsic granitoids as the protolith of R.A.T. and Dipeta siltstones. The Ti/Zr ratio of R.A.T. and Dipeta samples of less than 10, while, the higher La/Sc ratio of between 2.6 and 5.5 (for the R.A.T. and Dipeta respectively) indicate that both the R.A.T. and Dipeta are active continental and passive margin tectonic setting. Based on the geochemical variation with depth across the R.A.T. and Dipeta and their contact zone, a geochemical fingerprinting suggests that the ratio TiO2/Al2O3 appears to be useful and could be considered as a stratigraphic geochemical maker able to discriminate the R.A.T. and the Dipeta Subgroups during the geological mapping.
- Full Text:
- Date Issued: 2020
- Authors: Nkulu, Robert Kankomba
- Date: 2020
- Subjects: Petrogenesis -- Congo (Democratic Republic) , Analytical geochemistry -- Congo (Democratic Republic) , Copper ores -- Congo (Democratic Republic) , Ore deposits -- Congo (Democratic Republic) , Katangan Sequence , Geological mapping -- Congo (Democratic Republic) , Central African Copperbelt (Congo and Zambia) , Lufilian Arc , Neoproterozoic Katangan R.A.T. (Roches Argilo Talqueuse) Subgroup , Dipeta Subgroup
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/142772 , vital:38115
- Description: The Kinsevere and Nambulwa copper deposits in the Democratic Republic of Congo (D.R.C.) are set in the eastern side of the Neoproterozoic Katanga Supergroup, forming the Lufilian Arc, resulting from a cratonic collision between the Congo and the Kalahari Cratons (ca.620-570_Ma). The Katanga Supergroup was deposited in an extensional rift setting with a sedimentary thickness succession ranging between 7 to 10 km, sub-divided into: − the Roan, the Nguba and the Kundelungu Groups. The stratigraphic column of the Roan Group consists of the R.A.T. (Roche Argilo Talqueuse), the Mines, the Dipeta and the Mwashya Subgroups. Three major deformation phases have been described characterised by complex multiphase tectonics related to a curved superposition of folded, thrust and sheared blocks. The rocks of the R.A.T., Mines and Dipeta Subgroups are recognised as blocks that occur within a stratiform to discordant and diapiritic megabreccia. The blocks were rafted upward with salt tectonics, resulting in the juxtaposition with the hangingwall and the footwall terranes. Therefore, in that context it has been found that the Dipeta may appear overlying the R.A.T. Subgroup through the unconformity decollement surface of heterogeneous breccia. The petrographic observations made of the R.A.T. and Dipeta samples indicates in both units the presence of detrital quartz and feldspar that have been altered and replaced by sericite and muscovite minerals. Gypsum is intimately associated with magnesite, showing an evaporitic environment domain, while magnesite is common as alteration phase both in the R.A.T. and Dipeta Subgroups. Pyrophyllite has been observed in the Dipeta, resulting from reaction of silica with the Kaolinite at low temperature. Accessory detrital minerals include zircon, as well as xenotime intergrown with altered Fe-Ti-oxide hematite, forming complex textures with disseminated Ti-oxides both in R.A.T. and Dipeta units. Major and trace element geochemistry indicates that the Dipeta is more dolomitic and magnesite while the R.A.T. is clay-rich. The Ti2O value of Dipeta and R.A.T samples is relatively low, ranging between 0.36 and 0.69 wt.% respectively, which suggest highly evolved felsic material in the protolith. This is consistent with interpretation based on the Al2O3/TiO2 ratio, which ranges between 18 and 23 for the R.A.T. and Dipeta respectively, indicating an intermediate to felsic granitoids as the protolith of R.A.T. and Dipeta siltstones. The Ti/Zr ratio of R.A.T. and Dipeta samples of less than 10, while, the higher La/Sc ratio of between 2.6 and 5.5 (for the R.A.T. and Dipeta respectively) indicate that both the R.A.T. and Dipeta are active continental and passive margin tectonic setting. Based on the geochemical variation with depth across the R.A.T. and Dipeta and their contact zone, a geochemical fingerprinting suggests that the ratio TiO2/Al2O3 appears to be useful and could be considered as a stratigraphic geochemical maker able to discriminate the R.A.T. and the Dipeta Subgroups during the geological mapping.
- Full Text:
- Date Issued: 2020
Synthesis, characterization and evaluation of photophysical and electrochemical properties of ruthenium(II) complexes for dye-sensitized solar cells
- Authors: Adjogri, Shadrack John
- Date: 2018
- Subjects: Ruthenium Ruthenium compounds
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10353/17828 , vital:41363
- Description: Eight series of thirty (30) novel heteroleptic ruthenium(II) complexes were designed, synthesized and spectroscopically characterized, with the following general molecular formulae as [Ru(bdmpmar)(H2dcbpy)(NCS)]+, [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2,+, [Ru(bdmpmar)(vpbpp)(H2dcbpy)]2+,[Ru(H2dcbpy)2(N^)(NCS)]+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2], [Ru(H2dcbpy)(N^)(NCS)3]– and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ where bdmpmar is a tridentate ligand of N,N-bis(3, 5-dimethylpyrazol-1-yl-methyl) aromatic organic compound (such aromatic organic compounds(Ar) are anthranilic acid, 4-methoxy-2-nitroaniline, aniline, toluidine, cyclohexylamine and anisidine), vpdiinp represents a monodentate ligand of 11-(4-vinylphenyl)diindeno[1,2-b:2’,1’-e]pyridine, vpbpp represents a monodentate ligand of 4-(4-vinylphenyl)-2.6-bis(phenyl)pyridine and vptpy represents a tridentate ligand of 4’-(4-vinyl)-2,2’:6’,2’’-terpyridine. Meanwhile, N^ represents any of the monodentate ligands of either vpdiinp or vpbpp and (N^^^) represents any of the monodentate ligands either of vpdiinp or vpbpp or NCS as disclosed in series VIII. The complexes were characterized by conductivity measurement, solubility, melting point, UV-Vis, PL, FTIR (ATR), NMR, Cyclic and square wave voltammetry. Nine chelating ligands, comprising of six (6) tripodal chelating ligands, two (2) vinyl monodentate ligands and one (1) vinyl tridentate ligand, were used for the synthesis of ruthenium(II) complexes ATR-FTIR spectra of all the ruthenium(II) complexes measured as solid samples, exhibited fine resolution IR bands in region between 3473-3438 cm-1 of carboxylic group in H2dcbpy. The bands in the range 3040-2950 cm-1 were ascribed to C-H bond stretching for the CH3 groups. The coordination of NCS group in the sphere of ruthenium(II) complexes related to series I, IV, VI VII and one compound of series VIII was investigated by ATR-FTIR spectroscopy. Bands in the range of 2116-2106 cm-1 and 777-770 cm-1 are ascribed to the respective N=C and the C=S bond stretching vibration which confirms the N-coordination of the SCN group. For all the complexes, the stretching vibration of Ru-N bonding was between 466 and 411 cm-1 due to coordination of the nitrogen atoms of the ligands to ruthenium central metal atom. The introduction of the two vinyl monodentate ligands (vpdiinp and vpbpp) in the coordination sphere of [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2+, [Ru(bdmpmar) (vpbpp)(H2dcbpy)]2+, [Ru(H2dcbpy)2(N^)(NCS)]+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2], [Ru(H2dcbpy)(N^)(NCS)3]– and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ respectively, all related to series II, III, IV, V, VI, VII and two compounds of series VIII ruthenium(II) complexes, has been studied using the 1H and 13C NMR spectroscopy techniques. The 1H NMR spectra of series II-VII and the two compounds of series VIII of the ruthenium(II) complexes show multiplets in the aromatic region above 6 ppm due to the presence of either vpdiinp or vpbpp ligand, situated in different magnetic environment. However, no splitting pattern was observed in series I and part of VIII complexes possibly due to the absence vinyl monodentate subunits (vpdiinp and vpbpp) in series I and one of compound in series VIII ruthenium(II) complexes show no signals of complex splitting patterns. Carbon-13 NMR spectra data of series I to VIII ruthenium(II) complexes show most resonance signals range in the aromatic region of (δ 116.54-199.63ppm) corresponding to the molecular formulation of ruthenium(II) complexes incorporating 4,4-dicarboxy-2,2’-bipyridine, bdmpmar, vptpy, vpdiinp or vpbpp and NCS ligands respectively, depending on the intrinsic ligand variations. Carbon-13 NMR spectra data of series I, IV, VI VII and one compound in VIII show resonance peaks within the range 130-135 ppm are ascribed to NCS ligand confirming the presence of N-coordinated thiocyanate. Cyclic voltammograms of series I-IV and VI-VIII complexes display ruthenium-based oxidative peaks and the pyridines ligand-based reductive peaks. The redox behavior of complexes 4-12, 14-16, 18-20, 24-26 and 30 is dominated by the Ru(II)/R(III) redox couple in region (E1/2 between 0.53 and 1.18) and the pyridines ligand-based redox couples in the region between (E1/2 between −0.25 and −1.45). The photophysical property studies of the Ru(II) complexes are determined through the acquisitions of the absorption spectra, which tends to have profound effect on the short circuit current of DSSC. The absorption maxima were tuned by the introduction and variation of six (6) tripodal chelating ligands, two (2) vinyl monodentate ligands and one (1) vinyl tridentate ligand. From the studies, the results show that series IV, V, VI, VII and VIII complexes of molecular formula [Ru(H2dcbpy)2(N^)(NCS)]2+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2]2+, [Ru(H2dcbpy)(N^)(NCS)3]2+ and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ respectively, have higher and multiple local absorption maxima near-IR region than the complexes of series I, II and III of molecular [Ru(bdmpmar)(H2dcbpy)(NCS)]2,+, [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2,+, [Ru(bdmpmar)(vpbpp)(H2dcbpy)]2,+respectively.
- Full Text:
- Date Issued: 2018
- Authors: Adjogri, Shadrack John
- Date: 2018
- Subjects: Ruthenium Ruthenium compounds
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10353/17828 , vital:41363
- Description: Eight series of thirty (30) novel heteroleptic ruthenium(II) complexes were designed, synthesized and spectroscopically characterized, with the following general molecular formulae as [Ru(bdmpmar)(H2dcbpy)(NCS)]+, [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2,+, [Ru(bdmpmar)(vpbpp)(H2dcbpy)]2+,[Ru(H2dcbpy)2(N^)(NCS)]+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2], [Ru(H2dcbpy)(N^)(NCS)3]– and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ where bdmpmar is a tridentate ligand of N,N-bis(3, 5-dimethylpyrazol-1-yl-methyl) aromatic organic compound (such aromatic organic compounds(Ar) are anthranilic acid, 4-methoxy-2-nitroaniline, aniline, toluidine, cyclohexylamine and anisidine), vpdiinp represents a monodentate ligand of 11-(4-vinylphenyl)diindeno[1,2-b:2’,1’-e]pyridine, vpbpp represents a monodentate ligand of 4-(4-vinylphenyl)-2.6-bis(phenyl)pyridine and vptpy represents a tridentate ligand of 4’-(4-vinyl)-2,2’:6’,2’’-terpyridine. Meanwhile, N^ represents any of the monodentate ligands of either vpdiinp or vpbpp and (N^^^) represents any of the monodentate ligands either of vpdiinp or vpbpp or NCS as disclosed in series VIII. The complexes were characterized by conductivity measurement, solubility, melting point, UV-Vis, PL, FTIR (ATR), NMR, Cyclic and square wave voltammetry. Nine chelating ligands, comprising of six (6) tripodal chelating ligands, two (2) vinyl monodentate ligands and one (1) vinyl tridentate ligand, were used for the synthesis of ruthenium(II) complexes ATR-FTIR spectra of all the ruthenium(II) complexes measured as solid samples, exhibited fine resolution IR bands in region between 3473-3438 cm-1 of carboxylic group in H2dcbpy. The bands in the range 3040-2950 cm-1 were ascribed to C-H bond stretching for the CH3 groups. The coordination of NCS group in the sphere of ruthenium(II) complexes related to series I, IV, VI VII and one compound of series VIII was investigated by ATR-FTIR spectroscopy. Bands in the range of 2116-2106 cm-1 and 777-770 cm-1 are ascribed to the respective N=C and the C=S bond stretching vibration which confirms the N-coordination of the SCN group. For all the complexes, the stretching vibration of Ru-N bonding was between 466 and 411 cm-1 due to coordination of the nitrogen atoms of the ligands to ruthenium central metal atom. The introduction of the two vinyl monodentate ligands (vpdiinp and vpbpp) in the coordination sphere of [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2+, [Ru(bdmpmar) (vpbpp)(H2dcbpy)]2+, [Ru(H2dcbpy)2(N^)(NCS)]+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2], [Ru(H2dcbpy)(N^)(NCS)3]– and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ respectively, all related to series II, III, IV, V, VI, VII and two compounds of series VIII ruthenium(II) complexes, has been studied using the 1H and 13C NMR spectroscopy techniques. The 1H NMR spectra of series II-VII and the two compounds of series VIII of the ruthenium(II) complexes show multiplets in the aromatic region above 6 ppm due to the presence of either vpdiinp or vpbpp ligand, situated in different magnetic environment. However, no splitting pattern was observed in series I and part of VIII complexes possibly due to the absence vinyl monodentate subunits (vpdiinp and vpbpp) in series I and one of compound in series VIII ruthenium(II) complexes show no signals of complex splitting patterns. Carbon-13 NMR spectra data of series I to VIII ruthenium(II) complexes show most resonance signals range in the aromatic region of (δ 116.54-199.63ppm) corresponding to the molecular formulation of ruthenium(II) complexes incorporating 4,4-dicarboxy-2,2’-bipyridine, bdmpmar, vptpy, vpdiinp or vpbpp and NCS ligands respectively, depending on the intrinsic ligand variations. Carbon-13 NMR spectra data of series I, IV, VI VII and one compound in VIII show resonance peaks within the range 130-135 ppm are ascribed to NCS ligand confirming the presence of N-coordinated thiocyanate. Cyclic voltammograms of series I-IV and VI-VIII complexes display ruthenium-based oxidative peaks and the pyridines ligand-based reductive peaks. The redox behavior of complexes 4-12, 14-16, 18-20, 24-26 and 30 is dominated by the Ru(II)/R(III) redox couple in region (E1/2 between 0.53 and 1.18) and the pyridines ligand-based redox couples in the region between (E1/2 between −0.25 and −1.45). The photophysical property studies of the Ru(II) complexes are determined through the acquisitions of the absorption spectra, which tends to have profound effect on the short circuit current of DSSC. The absorption maxima were tuned by the introduction and variation of six (6) tripodal chelating ligands, two (2) vinyl monodentate ligands and one (1) vinyl tridentate ligand. From the studies, the results show that series IV, V, VI, VII and VIII complexes of molecular formula [Ru(H2dcbpy)2(N^)(NCS)]2+, [Ru(H2dcbpy)2(N^)2]2+, [Ru(H2dcbpy)(N^)2(NCS)2]2+, [Ru(H2dcbpy)(N^)(NCS)3]2+ and [Ru(vptpy)(H2dcbpy)(N^^^)]2+ respectively, have higher and multiple local absorption maxima near-IR region than the complexes of series I, II and III of molecular [Ru(bdmpmar)(H2dcbpy)(NCS)]2,+, [Ru(bdmpmar)(vpdiinp)(H2dcbpy)]2,+, [Ru(bdmpmar)(vpbpp)(H2dcbpy)]2,+respectively.
- Full Text:
- Date Issued: 2018
Rhenium complexes with multidentate imine-, amine-, thione-, thiol-, hydroxy- and carboxamide chelates
- Authors: Habarurema, Gratien
- Date: 2016
- Subjects: Rhenium Metal complexes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/12679 , vital:27106
- Description: This study entails the synthesis, spectroscopic and structural characterization of new rhenium complexes with multidentate imine-, amine-, thione-, thiol-, hydroxy- and carboxamide chelates in various oxidation states. Rhenium(I) and (V) complexes with imidazolidine, pyrimidine and bridging pyridyl derivatives are reported in Chapter 3. The reactions of the potential tridentate N,N,Odonor ligand 2,2'-dipyridylketone (dpk) with trans-[ReOCl3(PPh3)2], (n-Bu4N)[ReOCl4] and trans-[ReOI2(OEt)(PPh3)2] led to the isolation of cis-[ReOCl2(edpm)], cis-[ReOCl2(dpk.OH)] and [ReO3(dpk.OH)] respectively (see Scheme 1). The reaction of (E)-N-((pyridine-2-yl)methylene)benzo[d]thiazol-2-amine (pbt) with trans- [ReOCl3(PPh3)2] produced a mononuclear oxorhenium(V) complex cis- [ReOCl2(epm)(PPh3)]. Both dpk and pbt exhibited a nucleophilic attack by acetonitrile (for Hedpm), water (for dpk) and ethanol (for pbt) leading to chelates that act as uninegative tridentate N,N,O- and bidentate N,O-donor chelates respectively. The reaction of [Re(CO)5Cl] with 2,3-dihydro-2,2-di(pyridin-2-yl)-1H-benzo[d]imidazole (H2dpb), (2,6-diaza-cyclohex-1-enylolonium)2-aza-benzoate (H2den) and 2-(2-(pyridine-2-yl)imidazolidin-2-yl)pyridine (H2pip) (see Scheme 1) gave rise to novel rhenium(I) complexes fac-[Re(CO)3(H2dmb)Cl], fac-[Re(CO)3(Hhdm)] and fac-[Re(CO)3(H2pip)]Cl respectively. The monomeric cationic salt fac-[Re(CO)3(H2salbam)]Br and ligand-bridged dimer fac- (μ-H2salet)[Re(CO)3]2 complexes were formed by the reactions of [Re(CO)5X] (X = Br or Cl) with the potentially heptadentate Schiff base 2,2,2-tris (salicylideneimino)- triethylamine (H3salet; Scheme 2) respectively. The reactions of the potentially hexadentate ligands acting as tridentate monoanionic N,N,O- or N,O,O-donor chelates N1-(3-(2-hydroxy enzylideneamino) propylamino) ethyl)benzylidenepropane-1,3-diamine (H2salpd) and N,N -bis(salicylidene) -3,6-dioxa-1,8-diaminooctane (H2saldane) (Scheme 2) with [Re(CO)5Cl] led to the isolation of the mononuclear and dinuclear complexes fac-[Re(CO)3(Hsaldane)] and fac-(μ-salpd)[Re(CO)3]2 respectively. The reactions of [Re(CO)5Cl] with the tetradentate ligands 2-{[2-hydroxy-3-{[(E)-(2- hydroxyphenyl)-methylidene]amino}propyl)imino]methyl}phenol (H2hmp), 6-((6E)- ((3E)-3-((oxocyclohexa-2,4-dienyl)methyleneamino)-2-hydroxypropylimino)methyl)- cyclohexa-2,4-dienone (H2hcd.H2O) zwitterion and 2-((1E)-1-((E)-3-(2-hydoxyphenylmethylideneamino)propylimino)methyl)phenol (H2hdp) (see Scheme 2) resulted in the formation of the neutral fac-[Re(CO)3(Hamp)], fac-[Re(CO)3(Hhetp)] and fac- [Re(CO)3(Happ)] respectively. The treatment of 2-((3-(2-hydroxybenzylamino)-propylamino)methyl)phenol (H2hbp) with [Re(CO)3Cl] and trans-[ReOCl3(PPh3)2] gave the fac-[Re(CO)3(Hhbp)] and (μ-O)[ReO(hbp)]2 complexes. The reactions of the ligands H2hmp, H2hdp and H2hap (see Scheme 2) with trans-[ReOBr3(PPh3)2] and trans-[ReOI2(OEt)(PPh3)2] produced dinuclear oxo-bridged rhenium(V) complexes (μ-O)[ReO(hmp)]2, [(μ-O)[ReO(hdp)]2 and (μ-O)[ReO(hap)]2 respectively. The neutral and anionic binding modes of thiosemicarbazones to the fac-[Re(CO)3]+, cis- [ReO2]+ and trans-[ReO2]+ cores have been investigated in Chapter 6. The reactions of the potentially tridentate ligand 1-{1-(2- hydroxyphenyl)ethylidene}-4- phenylthiosemicarbazide (H2hpt) (see Scheme 3) with [Re(CO)5Cl], cis-[ReO2I(PPh3)2]cand trans-[ReO2(py)4]Cl led to the isolation of the complexes fac-[Re(CO)3(H2hpt)2]Cl, [Re(hipt)(Hipht)(PPh3)] and trans-[ReO(hpt)(Hhpt)] respectively. The X-ray crystal analysis of the complexes show that the ligand H2hpt exhibits decomposition, thiol-enol tautomerism and a thiolate-iminium zwitterionic process, and coordinates in the neutral form via its thione sulfur and nitrogen and anionic through the azo nitrogen, thiolate sulfur and acetophenolic oxygen. A series of nitrogen-heterocyclic amide-, acid-, thiol- and diol-based ligands as well as their related monomeric rhenium(III) and (V) complexes have also been studied (see Chapter 7). The reaction of N-(2-(pyrazine-2-carboxamido)phenyl)pyrazine-2- carboxamide (H2ppc) (Scheme 3) with trans-[ReOBr3(PPh3)2] yielded the complex trans- [ReBr2(Hppca)(PPh3)2]. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with pyridine-2,6-dicarboxylic acid (H2pda) produced the neutral oxorhenium(V) complexes [ReOX2(epca)(PPh3)]. The treatment of trans-[ReOBr3(PPh3)2] with 2-mercaptopyridine- 3-carboxylic acid (H2mpc) gave rise to the rhenium(III) complex [Re(empc)3(PPh3)]. The reaction of 2,6-bis(hydroxymethyl)pyridine (H2bhp) with trans-[ReOI2(EOt)(PPh3)2], trans-[ReOBr3(PPh3)2] and [Re(CO)5Cl] gave the complexes [ReO(Hbhp)2(PPh3)]I.PPh3, cis-[ReOBr2(Hbhp)(PPh3)] and fac-(μ- O)2[Re(CO)3(Hbhp)]2 respectively. Their X-ray crystal structures indicate that the ligand acts as a bidentate monoanionic N,O-donor chelate leaving a free aliphatic hydroxyl group.
- Full Text:
- Date Issued: 2016
- Authors: Habarurema, Gratien
- Date: 2016
- Subjects: Rhenium Metal complexes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/12679 , vital:27106
- Description: This study entails the synthesis, spectroscopic and structural characterization of new rhenium complexes with multidentate imine-, amine-, thione-, thiol-, hydroxy- and carboxamide chelates in various oxidation states. Rhenium(I) and (V) complexes with imidazolidine, pyrimidine and bridging pyridyl derivatives are reported in Chapter 3. The reactions of the potential tridentate N,N,Odonor ligand 2,2'-dipyridylketone (dpk) with trans-[ReOCl3(PPh3)2], (n-Bu4N)[ReOCl4] and trans-[ReOI2(OEt)(PPh3)2] led to the isolation of cis-[ReOCl2(edpm)], cis-[ReOCl2(dpk.OH)] and [ReO3(dpk.OH)] respectively (see Scheme 1). The reaction of (E)-N-((pyridine-2-yl)methylene)benzo[d]thiazol-2-amine (pbt) with trans- [ReOCl3(PPh3)2] produced a mononuclear oxorhenium(V) complex cis- [ReOCl2(epm)(PPh3)]. Both dpk and pbt exhibited a nucleophilic attack by acetonitrile (for Hedpm), water (for dpk) and ethanol (for pbt) leading to chelates that act as uninegative tridentate N,N,O- and bidentate N,O-donor chelates respectively. The reaction of [Re(CO)5Cl] with 2,3-dihydro-2,2-di(pyridin-2-yl)-1H-benzo[d]imidazole (H2dpb), (2,6-diaza-cyclohex-1-enylolonium)2-aza-benzoate (H2den) and 2-(2-(pyridine-2-yl)imidazolidin-2-yl)pyridine (H2pip) (see Scheme 1) gave rise to novel rhenium(I) complexes fac-[Re(CO)3(H2dmb)Cl], fac-[Re(CO)3(Hhdm)] and fac-[Re(CO)3(H2pip)]Cl respectively. The monomeric cationic salt fac-[Re(CO)3(H2salbam)]Br and ligand-bridged dimer fac- (μ-H2salet)[Re(CO)3]2 complexes were formed by the reactions of [Re(CO)5X] (X = Br or Cl) with the potentially heptadentate Schiff base 2,2,2-tris (salicylideneimino)- triethylamine (H3salet; Scheme 2) respectively. The reactions of the potentially hexadentate ligands acting as tridentate monoanionic N,N,O- or N,O,O-donor chelates N1-(3-(2-hydroxy enzylideneamino) propylamino) ethyl)benzylidenepropane-1,3-diamine (H2salpd) and N,N -bis(salicylidene) -3,6-dioxa-1,8-diaminooctane (H2saldane) (Scheme 2) with [Re(CO)5Cl] led to the isolation of the mononuclear and dinuclear complexes fac-[Re(CO)3(Hsaldane)] and fac-(μ-salpd)[Re(CO)3]2 respectively. The reactions of [Re(CO)5Cl] with the tetradentate ligands 2-{[2-hydroxy-3-{[(E)-(2- hydroxyphenyl)-methylidene]amino}propyl)imino]methyl}phenol (H2hmp), 6-((6E)- ((3E)-3-((oxocyclohexa-2,4-dienyl)methyleneamino)-2-hydroxypropylimino)methyl)- cyclohexa-2,4-dienone (H2hcd.H2O) zwitterion and 2-((1E)-1-((E)-3-(2-hydoxyphenylmethylideneamino)propylimino)methyl)phenol (H2hdp) (see Scheme 2) resulted in the formation of the neutral fac-[Re(CO)3(Hamp)], fac-[Re(CO)3(Hhetp)] and fac- [Re(CO)3(Happ)] respectively. The treatment of 2-((3-(2-hydroxybenzylamino)-propylamino)methyl)phenol (H2hbp) with [Re(CO)3Cl] and trans-[ReOCl3(PPh3)2] gave the fac-[Re(CO)3(Hhbp)] and (μ-O)[ReO(hbp)]2 complexes. The reactions of the ligands H2hmp, H2hdp and H2hap (see Scheme 2) with trans-[ReOBr3(PPh3)2] and trans-[ReOI2(OEt)(PPh3)2] produced dinuclear oxo-bridged rhenium(V) complexes (μ-O)[ReO(hmp)]2, [(μ-O)[ReO(hdp)]2 and (μ-O)[ReO(hap)]2 respectively. The neutral and anionic binding modes of thiosemicarbazones to the fac-[Re(CO)3]+, cis- [ReO2]+ and trans-[ReO2]+ cores have been investigated in Chapter 6. The reactions of the potentially tridentate ligand 1-{1-(2- hydroxyphenyl)ethylidene}-4- phenylthiosemicarbazide (H2hpt) (see Scheme 3) with [Re(CO)5Cl], cis-[ReO2I(PPh3)2]cand trans-[ReO2(py)4]Cl led to the isolation of the complexes fac-[Re(CO)3(H2hpt)2]Cl, [Re(hipt)(Hipht)(PPh3)] and trans-[ReO(hpt)(Hhpt)] respectively. The X-ray crystal analysis of the complexes show that the ligand H2hpt exhibits decomposition, thiol-enol tautomerism and a thiolate-iminium zwitterionic process, and coordinates in the neutral form via its thione sulfur and nitrogen and anionic through the azo nitrogen, thiolate sulfur and acetophenolic oxygen. A series of nitrogen-heterocyclic amide-, acid-, thiol- and diol-based ligands as well as their related monomeric rhenium(III) and (V) complexes have also been studied (see Chapter 7). The reaction of N-(2-(pyrazine-2-carboxamido)phenyl)pyrazine-2- carboxamide (H2ppc) (Scheme 3) with trans-[ReOBr3(PPh3)2] yielded the complex trans- [ReBr2(Hppca)(PPh3)2]. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with pyridine-2,6-dicarboxylic acid (H2pda) produced the neutral oxorhenium(V) complexes [ReOX2(epca)(PPh3)]. The treatment of trans-[ReOBr3(PPh3)2] with 2-mercaptopyridine- 3-carboxylic acid (H2mpc) gave rise to the rhenium(III) complex [Re(empc)3(PPh3)]. The reaction of 2,6-bis(hydroxymethyl)pyridine (H2bhp) with trans-[ReOI2(EOt)(PPh3)2], trans-[ReOBr3(PPh3)2] and [Re(CO)5Cl] gave the complexes [ReO(Hbhp)2(PPh3)]I.PPh3, cis-[ReOBr2(Hbhp)(PPh3)] and fac-(μ- O)2[Re(CO)3(Hbhp)]2 respectively. Their X-ray crystal structures indicate that the ligand acts as a bidentate monoanionic N,O-donor chelate leaving a free aliphatic hydroxyl group.
- Full Text:
- Date Issued: 2016
A stability-indicating high performance liquid chromatographic (HPLC) assay for the simultaneous determination of atorvastatin and amlodipine in commercial tablets
- Mohammadi, Ali, Rezanour, N, Ansari Dogaheh, M, Ghorbani Bidkorbeh, F, Hashem, M, Walker, Roderick B
- Authors: Mohammadi, Ali , Rezanour, N , Ansari Dogaheh, M , Ghorbani Bidkorbeh, F , Hashem, M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6403 , http://hdl.handle.net/10962/d1006340
- Description: A simple, rapid, precise and accurate isocratic reversed-phase stability-indicating HPLC method was developed and validated for the simultaneous determination of atorvastatin (AT) and amlodipine (AM) in commercial tablets. The method has shown adequate separation for AM, AT from their associated main impurities and their degradation products. Separation was achieved on a Perfectsil® Target ODS-3, 5 μm, 250 mm × 4.6 mm i.d. column using a mobile phase consisting of acetonitrile–0.025 M NaH2PO4 buffer (pH 4.5) (55:45, v/v) at a flow rate of 1 ml/min and UV detection at 237 nm. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The linearity of the proposed method was investigated in the range of 2–30 μg/ml (r = 0.9994) for AT and 1–20 μg/ml (r = 0.9993) for AM. The limits of detection were 0.65 μg/ml and 0.35 μg/ml for AT and AM, respectively. The limits of quantitation were 2 μg/ml and 1 μg/ml for AT and AM, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of AT and AM and the assay can thus be considered stability-indicating.
- Full Text:
- Date Issued: 2007
- Authors: Mohammadi, Ali , Rezanour, N , Ansari Dogaheh, M , Ghorbani Bidkorbeh, F , Hashem, M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6403 , http://hdl.handle.net/10962/d1006340
- Description: A simple, rapid, precise and accurate isocratic reversed-phase stability-indicating HPLC method was developed and validated for the simultaneous determination of atorvastatin (AT) and amlodipine (AM) in commercial tablets. The method has shown adequate separation for AM, AT from their associated main impurities and their degradation products. Separation was achieved on a Perfectsil® Target ODS-3, 5 μm, 250 mm × 4.6 mm i.d. column using a mobile phase consisting of acetonitrile–0.025 M NaH2PO4 buffer (pH 4.5) (55:45, v/v) at a flow rate of 1 ml/min and UV detection at 237 nm. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The linearity of the proposed method was investigated in the range of 2–30 μg/ml (r = 0.9994) for AT and 1–20 μg/ml (r = 0.9993) for AM. The limits of detection were 0.65 μg/ml and 0.35 μg/ml for AT and AM, respectively. The limits of quantitation were 2 μg/ml and 1 μg/ml for AT and AM, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of AT and AM and the assay can thus be considered stability-indicating.
- Full Text:
- Date Issued: 2007
Mechanistic studies of unusual Miruta-Baylis-Hillman reactions
- Authors: Nyoni, Dubekile
- Date: 2012
- Subjects: Chemical reactions Benzaldehyde Acrylonitrile Methyl acrylate Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4400 , http://hdl.handle.net/10962/d1006692
- Description: This study has focussed on the application of synthetic, kinetic and exploratory theoretical methods in elucidating the reaction mechanisms of four Morita-Baylis-Hillman (MBH) type reactions, viz, i) the reactions of the disulfide 2,2'-dithiodibenzaldehyde with various activated alkenes in the presence of DBU and Ph₃P, ii) the reactions of chromone-3-carbaldehydes with MVK, iii) the reactions of chromone-2-carbaldehydes with acrylonitrile and iv) with methyl acrylate. Attention has also been given to the origin of the observed regioselectivity in Michaelis-Arbuzov reactions of 3-(halomethyl)coumarins. Cleavage of the sulfur-sulfur bond of aryl and heteroaryl disulfides by the nitrogen nucleophile DBU has been demonstrated, and a dramatic increase in the rate of tandem MBH and disulfide cleavage reactions of 2,2'-dithiodibenzaldehyde with the activated alkenes, MVK, EVK, acrylonitrile, methyl acrylate and tert-butyl acrylate has been achieved through the use of the dual organo-catalyst system, DBU-Ph₃P – an improvement accompanied by an increase in the yields of the isolated products. Detailed NMR-based kinetic studies have been conducted on the DBU-catalysed reactions of 2,2'-dithiodibenzaldehyde with MVK and methyl acrylate, and a theoretical kinetic model has been developed and complementary computational studies using Gaussian 03, at the DFT-B3LYP/6-31G(d) level of theory have provided valuable insights into the mechanism of these complex transformations. Reactions of chromone-3-carbaldehydes with MVK to afford chromone dimers and tricyclic products have been repeated, and a novel, intermediate MBH adduct has been isolated. The mechanisms of the competing pathways have been elucidated by DFT calculations and the development of a detailed theoretical kinetic model has ensued. Unusual transformations in MBH-type reactions of chromone-2-carbaldehydes with acrylonitrile and methyl acrylate have been explored and the structures of the unexpected products have been established using 1- and 2-D NMR, HRMS and X-ray crystallographic techniques. Attention has also been given to the synthesis of 3-(halomethyl)coumarins via the MBH reaction, and their subsequent Michaelis-Arbuzov reactions with triethyl phosphite. An exploratory study of the kinetics of the phosphonation reaction has been undertaken and the regio-selectivity of nucleophilic attack at the 4- and 1'-positions in the 3-chloro- and 3-(iodomethyl)coumarins has been investigated by calculating Mulliken charges, LUMO surfaces and Fukui condensed local softness functions.
- Full Text:
- Date Issued: 2012
- Authors: Nyoni, Dubekile
- Date: 2012
- Subjects: Chemical reactions Benzaldehyde Acrylonitrile Methyl acrylate Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4400 , http://hdl.handle.net/10962/d1006692
- Description: This study has focussed on the application of synthetic, kinetic and exploratory theoretical methods in elucidating the reaction mechanisms of four Morita-Baylis-Hillman (MBH) type reactions, viz, i) the reactions of the disulfide 2,2'-dithiodibenzaldehyde with various activated alkenes in the presence of DBU and Ph₃P, ii) the reactions of chromone-3-carbaldehydes with MVK, iii) the reactions of chromone-2-carbaldehydes with acrylonitrile and iv) with methyl acrylate. Attention has also been given to the origin of the observed regioselectivity in Michaelis-Arbuzov reactions of 3-(halomethyl)coumarins. Cleavage of the sulfur-sulfur bond of aryl and heteroaryl disulfides by the nitrogen nucleophile DBU has been demonstrated, and a dramatic increase in the rate of tandem MBH and disulfide cleavage reactions of 2,2'-dithiodibenzaldehyde with the activated alkenes, MVK, EVK, acrylonitrile, methyl acrylate and tert-butyl acrylate has been achieved through the use of the dual organo-catalyst system, DBU-Ph₃P – an improvement accompanied by an increase in the yields of the isolated products. Detailed NMR-based kinetic studies have been conducted on the DBU-catalysed reactions of 2,2'-dithiodibenzaldehyde with MVK and methyl acrylate, and a theoretical kinetic model has been developed and complementary computational studies using Gaussian 03, at the DFT-B3LYP/6-31G(d) level of theory have provided valuable insights into the mechanism of these complex transformations. Reactions of chromone-3-carbaldehydes with MVK to afford chromone dimers and tricyclic products have been repeated, and a novel, intermediate MBH adduct has been isolated. The mechanisms of the competing pathways have been elucidated by DFT calculations and the development of a detailed theoretical kinetic model has ensued. Unusual transformations in MBH-type reactions of chromone-2-carbaldehydes with acrylonitrile and methyl acrylate have been explored and the structures of the unexpected products have been established using 1- and 2-D NMR, HRMS and X-ray crystallographic techniques. Attention has also been given to the synthesis of 3-(halomethyl)coumarins via the MBH reaction, and their subsequent Michaelis-Arbuzov reactions with triethyl phosphite. An exploratory study of the kinetics of the phosphonation reaction has been undertaken and the regio-selectivity of nucleophilic attack at the 4- and 1'-positions in the 3-chloro- and 3-(iodomethyl)coumarins has been investigated by calculating Mulliken charges, LUMO surfaces and Fukui condensed local softness functions.
- Full Text:
- Date Issued: 2012
In vitro evaluation of antimicrobial and antioxidant activities of olea europaea subsp. africana and euryops brevipapposus used by Cala community folkloric medicine for the management of infections associated with chronic non-communicable diseases
- Authors: Adegborioye, Abiodun
- Date: 2016
- Subjects: Antioxidants Medicinal plants Traditional medicine -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/4869 , vital:28624
- Description: Chronic non-communicable diseses are a global public health challenge that continuously threatens the development and health of humans. Risk factors such as unbalanced diet-the high consumption of processed food or food from animal origin are responsible for NCDs. NCDs result in weakened immune system, making the host susceptible to opportunistic infections. Thus, the NCDs burden is most times chronic and multiple with the illness and suffering of the affected person numerous. The lack of cure for NCDs, the high cost of drugs, their high side-effects, and the emergence of multiple drug resistance has given rise to the investigation of other sources for therapeutic cure such as medicinal plants. The ethanol, n-hexane and ethyl acetate extracts of Olea europaea were analysed for their antioxidant and antimicrobial activities. The essential oil was also analysed for their chemical constituents. The n-hexane extracts of O. europaea exhibited no inhibition against all of the microorganisms tested, while the ethyl acetate and ethanol extracts exhibited inhibition, with minimum inhibitory concentration values between 0.625 mg/ml to 1.25 mg/ml. The ethanol leaf and ethyl acetate stem extracts exhibited significant activity in the inhibition of 2, 2-azinobis-(3-ethylbenzothiazolin - 6-sulfonic acid diammonium salt (ABTS) free radical, the n-hexane leaf extract had the overall significant lipid peroxidation inhibition activity, while in the inhibition of 2, 2- diphenyl-1-picrylhydrazyl radical (DPPH), the ethanol and ethyl acetate leaf extracts had strong activity. Nonanal, phytol, α-Pinene, α-Phellandrene, spatulenol and farnesol were some of chemical components identified after the GC-MS analysis of O. europaea oil. In the final part of the dissertation, Euryops brevipapposus essential oil was assessed for the antioxidant activities using free radical scavenging assays. In addition to this, the antimicrobial activities were assessed and the chemical composition was analysed using GC-MS. The essential oil demonstrated significant antioxidant activity against 2, 2-diphenyl-2-picryl-hydrazyl free radical (DPPH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and lipid peroxides with IC50 value of 0.0000000671 mg/ml, 1.05 mg/ml, and 1.170 mg/ml respectively. The essential oil also showed significant activity against all microorganisms tested with minimum inhibitory concentration (MIC) values between 0.055 mg/ml to 0.5 mg/ml. α-pinene, α- Phellandrene, germacrene D, β-pinene, trans- β.-Ocimene, bicyclogermacrene and β -Phellandrene were some of the chemical compounds identified in E. brevipapposus oil. The study has shown that E. brevipapposus and O. europaea are abundant in phytochemical compounds which were thought to be the root cause for the activities demonstrated. Therefore, these therapeutic properties observed validate and elucidate the traditional usage of the both plants in the treatment /management of diseases.
- Full Text:
- Date Issued: 2016
- Authors: Adegborioye, Abiodun
- Date: 2016
- Subjects: Antioxidants Medicinal plants Traditional medicine -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/4869 , vital:28624
- Description: Chronic non-communicable diseses are a global public health challenge that continuously threatens the development and health of humans. Risk factors such as unbalanced diet-the high consumption of processed food or food from animal origin are responsible for NCDs. NCDs result in weakened immune system, making the host susceptible to opportunistic infections. Thus, the NCDs burden is most times chronic and multiple with the illness and suffering of the affected person numerous. The lack of cure for NCDs, the high cost of drugs, their high side-effects, and the emergence of multiple drug resistance has given rise to the investigation of other sources for therapeutic cure such as medicinal plants. The ethanol, n-hexane and ethyl acetate extracts of Olea europaea were analysed for their antioxidant and antimicrobial activities. The essential oil was also analysed for their chemical constituents. The n-hexane extracts of O. europaea exhibited no inhibition against all of the microorganisms tested, while the ethyl acetate and ethanol extracts exhibited inhibition, with minimum inhibitory concentration values between 0.625 mg/ml to 1.25 mg/ml. The ethanol leaf and ethyl acetate stem extracts exhibited significant activity in the inhibition of 2, 2-azinobis-(3-ethylbenzothiazolin - 6-sulfonic acid diammonium salt (ABTS) free radical, the n-hexane leaf extract had the overall significant lipid peroxidation inhibition activity, while in the inhibition of 2, 2- diphenyl-1-picrylhydrazyl radical (DPPH), the ethanol and ethyl acetate leaf extracts had strong activity. Nonanal, phytol, α-Pinene, α-Phellandrene, spatulenol and farnesol were some of chemical components identified after the GC-MS analysis of O. europaea oil. In the final part of the dissertation, Euryops brevipapposus essential oil was assessed for the antioxidant activities using free radical scavenging assays. In addition to this, the antimicrobial activities were assessed and the chemical composition was analysed using GC-MS. The essential oil demonstrated significant antioxidant activity against 2, 2-diphenyl-2-picryl-hydrazyl free radical (DPPH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and lipid peroxides with IC50 value of 0.0000000671 mg/ml, 1.05 mg/ml, and 1.170 mg/ml respectively. The essential oil also showed significant activity against all microorganisms tested with minimum inhibitory concentration (MIC) values between 0.055 mg/ml to 0.5 mg/ml. α-pinene, α- Phellandrene, germacrene D, β-pinene, trans- β.-Ocimene, bicyclogermacrene and β -Phellandrene were some of the chemical compounds identified in E. brevipapposus oil. The study has shown that E. brevipapposus and O. europaea are abundant in phytochemical compounds which were thought to be the root cause for the activities demonstrated. Therefore, these therapeutic properties observed validate and elucidate the traditional usage of the both plants in the treatment /management of diseases.
- Full Text:
- Date Issued: 2016
Improved Stability of Rifampicin in the Presence of Gastric-Resistant Isoniazid Microspheres in Acidic Media
- Mwila, Chiluba, Walker, Roderick B
- Authors: Mwila, Chiluba , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183210 , vital:43929 , xlink:href="https://doi.org/10.3390/pharmaceutics12030234"
- Description: The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
- Full Text:
- Date Issued: 2020
- Authors: Mwila, Chiluba , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183210 , vital:43929 , xlink:href="https://doi.org/10.3390/pharmaceutics12030234"
- Description: The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit® L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
- Full Text:
- Date Issued: 2020
Isolation and characterization of extracts of Rosmarinus officinalis l. And comparative evaluation of its antimicrobial activity and selected types of antibiotics against some bacteria species
- Authors: Gbede,Remi
- Date: 2019
- Subjects: Rosmarinus Essences and essential oils Lamiaceae Medicinal plants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/19142 , vital:39875
- Description: Rosmarinus officinalis L. is known extensively for its multifunctional purposes. The essential oil has been widely used in cosmeceuticals and several ethnopharmacological values. In vitro studies have demonstrated the antibacterial activity of essential oils (EOs) of Rosmarinus officinalis L. against Staphylococcus aureus ATCC 25923, Vibrio cholerae DSM 19283, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853 and Bacillus cereus. These different bacteria were screened against antibiotics such as Tetracycline, Ampicillin Sodium salt, Erythromycin and Amoxicillin, and some standards namely rosmarinic acid, carnosic acid and carnosol, and also against the methanol, acetone, chloroform and dichloromethane extracts of rosemary. The essential oils of Rosmarinus officinalis L. showed significant inhibitory properties compared to antibiotics with various degrees of growth inhibition. The standards exhibited some activities against the organisms. The GC/MS analysis of the essential oil revealed 34 compounds present with most components acting in synergy to bring about antibacterial activities. The antiplasmodial and cytotoxic activities of two leaf extracts of Rosmarinus officinalis (with hexane and dichloromethane as solvents) using standard procedure were studied. The findings justify the claims on the efficacy of plants for therapeutic uses for antifungal, antibacterial and anti-inflammatory properties. Antiplasmodial activity of Rosmarinus officinalis recorded IC50 values of 9.99 µg/ml and 9.76 µg/ml in hexane and dichloromethane respectively.
- Full Text:
- Date Issued: 2019
- Authors: Gbede,Remi
- Date: 2019
- Subjects: Rosmarinus Essences and essential oils Lamiaceae Medicinal plants
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/19142 , vital:39875
- Description: Rosmarinus officinalis L. is known extensively for its multifunctional purposes. The essential oil has been widely used in cosmeceuticals and several ethnopharmacological values. In vitro studies have demonstrated the antibacterial activity of essential oils (EOs) of Rosmarinus officinalis L. against Staphylococcus aureus ATCC 25923, Vibrio cholerae DSM 19283, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853 and Bacillus cereus. These different bacteria were screened against antibiotics such as Tetracycline, Ampicillin Sodium salt, Erythromycin and Amoxicillin, and some standards namely rosmarinic acid, carnosic acid and carnosol, and also against the methanol, acetone, chloroform and dichloromethane extracts of rosemary. The essential oils of Rosmarinus officinalis L. showed significant inhibitory properties compared to antibiotics with various degrees of growth inhibition. The standards exhibited some activities against the organisms. The GC/MS analysis of the essential oil revealed 34 compounds present with most components acting in synergy to bring about antibacterial activities. The antiplasmodial and cytotoxic activities of two leaf extracts of Rosmarinus officinalis (with hexane and dichloromethane as solvents) using standard procedure were studied. The findings justify the claims on the efficacy of plants for therapeutic uses for antifungal, antibacterial and anti-inflammatory properties. Antiplasmodial activity of Rosmarinus officinalis recorded IC50 values of 9.99 µg/ml and 9.76 µg/ml in hexane and dichloromethane respectively.
- Full Text:
- Date Issued: 2019
Synthesis, characterisation and antitumour activities of lanthanide complexes with hydrazones and carboxylic acid ligands
- Authors: Madanhire, Tatenda
- Date: 2020
- Subjects: Organic acids
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/48456 , vital:40878
- Description: The tridentate hydrazone ligands, (E)-N'-(2-hydroxybenzylidene)benzohydrazide (H2phen) and (E)-N'-(2-hydroxybenzylidene)nicotinohydrazide (H2Nic), were synthesised and complexed to Ln(III) acetates. The centrosymmetric, acetato-bridged dinuclear coordination compounds with the formulae, [La2(Hphen)2(OAc)4(H2O)2]·DMF·H2O (1), [Ln2(HNic)2(OAc)4(H2O)2]·DMF·H2O (Ln = La (2) and Nd (3)) and [Ln2(HNic)2(OAc)4(H2O)2]·DMF (Ln = Er (4) and Yb (5)) were isolated and characterised by elemental analyses, IR spectroscopy, UV-Vis spectroscopy, X-ray diffraction studies and SHAPE 2.1. The nine-coordinate complexes 1–3 crystallise in the triclinic space group P-1, with the metal centres having the distorted spherical capped square antiprism geometry (C4v), while the eight-coordinate Er(III) and Yb(III) complexes (monoclinic system, space group P21/c) display the geometry of distorted triangular dodecahedron (D2d). Geometry optimisation of the monoanionic forms of the hydrazone ligands (Hphen– and HNic– ) were performed using Density Functional Theory (DFT) with Becke’s three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with augcc-pVTZ basis set. Natural population analysis (NPA) and molecular electrostatic potential (MEP) maps indicated that the most preferred sites for electrophilic attack in the anionic ligands are the phenolate and carbonyl oxygens, and the azomethine nitrogens. The evaluation of the cytotoxic activity of the compounds on breast cancer (MCF-7), the endometrial carcinoma (HEC-1A) and the human monocytic (THP-1) cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the hydrazone ligands and complexes 1–4 are partially cytotoxic against MCF-7 cells, while the Schiff bases and complexes 3–5 significantly inhibit cell growth in HEC-1A cells. The complexation reactions of Ce(III), Nd(III), Gd(III) and Er(III) with the chelating/ bridging monoanionic ligand N-(2,6-dimethylphenyl)oxamate (Hpma– ) in basic media were performed in view of the potential applications of oxamate derivatives as cytotoxic agents. The coordination compounds were characterised by different Abstract T. Madanhire Nelson Mandela University xxvi physico-chemical techniques: elemental analysis, conductivity measurements, IR, 1 H NMR and UV-Vis-NIR spectroscopy. The anionic Hpma– was obtained through conversion of the proligand ethyl (2,6-dimethylphenylcarbamoyl)formate (Hdmp). The reactions afforded lanthanide(III)–oxamate coordination polymers of formulae: {[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n (Ln = Ce (1) and Nd (2)), {[Gd2(Hpma)6(MeOH)4]∙6MeOH}n (3), {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n (4) and [Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd (5) and Gd (6)). The polymeric complexes feature Ln-Hpma moieties bridged by μ2-η 1 :η 1 :η 1 Hpma– , giving onedimensional zig-zag chains of the –Ln–O–C–O–Ln– type. Atomic charge analysis and the MEP map of the Hpma– moiety done using the DFT/B3LYP method were found to be consistent with the chelating and bridging modes of the anionic ligand through all the oxygen atoms. The evaluation of the cytotoxic activities of the metal salts, the proligand and the novel lanthanide complexes on MCF-7, HEC-1A and THP-1 cell lines revealed that only the rare-earth metal salts [Ce(NO3)3∙6H2O] and [Nd(NO3)3∙6H2O] showed modest cytotoxicity against MCF-7 and HEC-1A cells, respectively.
- Full Text:
- Date Issued: 2020
- Authors: Madanhire, Tatenda
- Date: 2020
- Subjects: Organic acids
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/48456 , vital:40878
- Description: The tridentate hydrazone ligands, (E)-N'-(2-hydroxybenzylidene)benzohydrazide (H2phen) and (E)-N'-(2-hydroxybenzylidene)nicotinohydrazide (H2Nic), were synthesised and complexed to Ln(III) acetates. The centrosymmetric, acetato-bridged dinuclear coordination compounds with the formulae, [La2(Hphen)2(OAc)4(H2O)2]·DMF·H2O (1), [Ln2(HNic)2(OAc)4(H2O)2]·DMF·H2O (Ln = La (2) and Nd (3)) and [Ln2(HNic)2(OAc)4(H2O)2]·DMF (Ln = Er (4) and Yb (5)) were isolated and characterised by elemental analyses, IR spectroscopy, UV-Vis spectroscopy, X-ray diffraction studies and SHAPE 2.1. The nine-coordinate complexes 1–3 crystallise in the triclinic space group P-1, with the metal centres having the distorted spherical capped square antiprism geometry (C4v), while the eight-coordinate Er(III) and Yb(III) complexes (monoclinic system, space group P21/c) display the geometry of distorted triangular dodecahedron (D2d). Geometry optimisation of the monoanionic forms of the hydrazone ligands (Hphen– and HNic– ) were performed using Density Functional Theory (DFT) with Becke’s three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with augcc-pVTZ basis set. Natural population analysis (NPA) and molecular electrostatic potential (MEP) maps indicated that the most preferred sites for electrophilic attack in the anionic ligands are the phenolate and carbonyl oxygens, and the azomethine nitrogens. The evaluation of the cytotoxic activity of the compounds on breast cancer (MCF-7), the endometrial carcinoma (HEC-1A) and the human monocytic (THP-1) cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the hydrazone ligands and complexes 1–4 are partially cytotoxic against MCF-7 cells, while the Schiff bases and complexes 3–5 significantly inhibit cell growth in HEC-1A cells. The complexation reactions of Ce(III), Nd(III), Gd(III) and Er(III) with the chelating/ bridging monoanionic ligand N-(2,6-dimethylphenyl)oxamate (Hpma– ) in basic media were performed in view of the potential applications of oxamate derivatives as cytotoxic agents. The coordination compounds were characterised by different Abstract T. Madanhire Nelson Mandela University xxvi physico-chemical techniques: elemental analysis, conductivity measurements, IR, 1 H NMR and UV-Vis-NIR spectroscopy. The anionic Hpma– was obtained through conversion of the proligand ethyl (2,6-dimethylphenylcarbamoyl)formate (Hdmp). The reactions afforded lanthanide(III)–oxamate coordination polymers of formulae: {[Ln(Hpma)3(MeOH)(H2O)]∙2MeOH}n (Ln = Ce (1) and Nd (2)), {[Gd2(Hpma)6(MeOH)4]∙6MeOH}n (3), {[Er2(Hpma)6(MeOH)(H2O)3]∙2MeOH}n (4) and [Ln2Na2(Hpma)8(EtOH)(H2O)6]n (Ln = Nd (5) and Gd (6)). The polymeric complexes feature Ln-Hpma moieties bridged by μ2-η 1 :η 1 :η 1 Hpma– , giving onedimensional zig-zag chains of the –Ln–O–C–O–Ln– type. Atomic charge analysis and the MEP map of the Hpma– moiety done using the DFT/B3LYP method were found to be consistent with the chelating and bridging modes of the anionic ligand through all the oxygen atoms. The evaluation of the cytotoxic activities of the metal salts, the proligand and the novel lanthanide complexes on MCF-7, HEC-1A and THP-1 cell lines revealed that only the rare-earth metal salts [Ce(NO3)3∙6H2O] and [Nd(NO3)3∙6H2O] showed modest cytotoxicity against MCF-7 and HEC-1A cells, respectively.
- Full Text:
- Date Issued: 2020
A study of a class of invariant optimal control problems on the Euclidean group SE(2)
- Authors: Adams, Ross Montague
- Date: 2011
- Subjects: Matrix groups Lie groups Extremal problems (Mathematics) Maximum principles (Mathematics) Hamilton-Jacobi equations Lyapunov stability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5420 , http://hdl.handle.net/10962/d1006060
- Description: The aim of this thesis is to study a class of left-invariant optimal control problems on the matrix Lie group SE(2). We classify, under detached feedback equivalence, all controllable (left-invariant) control affine systems on SE(2). This result produces six types of control affine systems on SE(2). Hence, we study six associated left-invariant optimal control problems on SE(2). A left-invariant optimal control problem consists of minimizing a cost functional over the trajectory-control pairs of a left-invariant control system subject to appropriate boundary conditions. Each control problem is lifted from SE(2) to T*SE(2) ≅ SE(2) x se (2)*and then reduced to a problem on se (2)*. The maximum principle is used to obtain the optimal control and Hamiltonian corresponding to the normal extremals. Then we derive the (reduced) extremal equations on se (2)*. These equations are explicitly integrated by trigonometric and Jacobi elliptic functions. Finally, we fully classify, under Lyapunov stability, the equilibrium states of the normal extremal equations for each of the six types under consideration.
- Full Text:
- Date Issued: 2011
- Authors: Adams, Ross Montague
- Date: 2011
- Subjects: Matrix groups Lie groups Extremal problems (Mathematics) Maximum principles (Mathematics) Hamilton-Jacobi equations Lyapunov stability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5420 , http://hdl.handle.net/10962/d1006060
- Description: The aim of this thesis is to study a class of left-invariant optimal control problems on the matrix Lie group SE(2). We classify, under detached feedback equivalence, all controllable (left-invariant) control affine systems on SE(2). This result produces six types of control affine systems on SE(2). Hence, we study six associated left-invariant optimal control problems on SE(2). A left-invariant optimal control problem consists of minimizing a cost functional over the trajectory-control pairs of a left-invariant control system subject to appropriate boundary conditions. Each control problem is lifted from SE(2) to T*SE(2) ≅ SE(2) x se (2)*and then reduced to a problem on se (2)*. The maximum principle is used to obtain the optimal control and Hamiltonian corresponding to the normal extremals. Then we derive the (reduced) extremal equations on se (2)*. These equations are explicitly integrated by trigonometric and Jacobi elliptic functions. Finally, we fully classify, under Lyapunov stability, the equilibrium states of the normal extremal equations for each of the six types under consideration.
- Full Text:
- Date Issued: 2011
An investigation of parameter relationships in a high-speed digital multimedia environment
- Authors: Chigwamba, Nyasha
- Date: 2014
- Subjects: Multimedia communications , Digital communications , Local area networks (Computer networks) , Computer network architectures , Computer network protocols , Computer sound processing , Sound -- Recording and reproducing -- Digital techniques
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4725 , http://hdl.handle.net/10962/d1021153
- Description: With the rapid adoption of multimedia network technologies, a number of companies and standards bodies are introducing technologies that enhance user experience in networked multimedia environments. These technologies focus on device discovery, connection management, control, and monitoring. This study focused on control and monitoring. Multimedia networks make it possible for devices that are part of the same network to reside in different physical locations. These devices contain parameters that are used to control particular features, such as speaker volume, bass, amplifier gain, and video resolution. It is often necessary for changes in one parameter to affect other parameters, such as a synchronised change between volume and bass parameters, or collective control of multiple parameters. Thus, relationships are required between the parameters. In addition, some devices contain parameters, such as voltage, temperature, and audio level, that require constant monitoring to enable corrective action when thresholds are exceeded. Therefore, a mechanism for monitoring networked devices is required. This thesis proposes relationships that are essential for the proper functioning of a multimedia network and that should, therefore, be incorporated in standard form into a protocol, such that all devices can depend on them. Implementation mechanisms for these relationships were created. Parameter grouping and monitoring capabilities within mixing console implementations and existing control protocols were reviewed. A number of requirements for parameter grouping and monitoring were derived from this review. These requirements include a formal classification of relationship types, the ability to create relationships between parameters with different underlying value units, the ability to create relationships between parameters residing on different devices on a network, and the use of an event-driven mechanism for parameter monitoring. These requirements were the criteria used to govern the implementation mechanisms that were created as part of this study. Parameter grouping and monitoring mechanisms were implemented for the XFN protocol. The mechanisms implemented fulfil the requirements derived from the review of capabilities of mixing consoles and existing control protocols. The formal classification of relationship types was implemented within XFN parameters using lists that keep track of the relationships between each XFN parameter and other XFN parameters that reside on the same device or on other devices on the network. A common value unit, known as the global unit, was defined for use as the value format within value update messages between XFN parameters that have relationships. Mapping tables were used to translate the global unit values to application-specific (universal) units, such as decibels (dB). A mechanism for bulk parameter retrieval within the XFN protocol was augmented to produce an event-driven mechanism for parameter monitoring. These implementation mechanisms were applied to an XFN-protocol-compliant graphical control application to demonstrate their usage within an end user context. At the time of this study, the XFN protocol was undergoing standardisation within the Audio Engineering Society. The AES-64 standard has now been approved. Most of the implementation mechanisms resulting from this study have been incorporated into this standard.
- Full Text:
- Date Issued: 2014
- Authors: Chigwamba, Nyasha
- Date: 2014
- Subjects: Multimedia communications , Digital communications , Local area networks (Computer networks) , Computer network architectures , Computer network protocols , Computer sound processing , Sound -- Recording and reproducing -- Digital techniques
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4725 , http://hdl.handle.net/10962/d1021153
- Description: With the rapid adoption of multimedia network technologies, a number of companies and standards bodies are introducing technologies that enhance user experience in networked multimedia environments. These technologies focus on device discovery, connection management, control, and monitoring. This study focused on control and monitoring. Multimedia networks make it possible for devices that are part of the same network to reside in different physical locations. These devices contain parameters that are used to control particular features, such as speaker volume, bass, amplifier gain, and video resolution. It is often necessary for changes in one parameter to affect other parameters, such as a synchronised change between volume and bass parameters, or collective control of multiple parameters. Thus, relationships are required between the parameters. In addition, some devices contain parameters, such as voltage, temperature, and audio level, that require constant monitoring to enable corrective action when thresholds are exceeded. Therefore, a mechanism for monitoring networked devices is required. This thesis proposes relationships that are essential for the proper functioning of a multimedia network and that should, therefore, be incorporated in standard form into a protocol, such that all devices can depend on them. Implementation mechanisms for these relationships were created. Parameter grouping and monitoring capabilities within mixing console implementations and existing control protocols were reviewed. A number of requirements for parameter grouping and monitoring were derived from this review. These requirements include a formal classification of relationship types, the ability to create relationships between parameters with different underlying value units, the ability to create relationships between parameters residing on different devices on a network, and the use of an event-driven mechanism for parameter monitoring. These requirements were the criteria used to govern the implementation mechanisms that were created as part of this study. Parameter grouping and monitoring mechanisms were implemented for the XFN protocol. The mechanisms implemented fulfil the requirements derived from the review of capabilities of mixing consoles and existing control protocols. The formal classification of relationship types was implemented within XFN parameters using lists that keep track of the relationships between each XFN parameter and other XFN parameters that reside on the same device or on other devices on the network. A common value unit, known as the global unit, was defined for use as the value format within value update messages between XFN parameters that have relationships. Mapping tables were used to translate the global unit values to application-specific (universal) units, such as decibels (dB). A mechanism for bulk parameter retrieval within the XFN protocol was augmented to produce an event-driven mechanism for parameter monitoring. These implementation mechanisms were applied to an XFN-protocol-compliant graphical control application to demonstrate their usage within an end user context. At the time of this study, the XFN protocol was undergoing standardisation within the Audio Engineering Society. The AES-64 standard has now been approved. Most of the implementation mechanisms resulting from this study have been incorporated into this standard.
- Full Text:
- Date Issued: 2014
Synthesis, characterization, and biological studies of pyrazolone Schiff bases and their transition metal complexes
- Authors: Idemudia, Omoruyi Gold
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD (Chemistry)
- Identifier: vital:11340 , http://hdl.handle.net/10353/d1016068
- Description: Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.
- Full Text:
- Date Issued: 2014
- Authors: Idemudia, Omoruyi Gold
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD (Chemistry)
- Identifier: vital:11340 , http://hdl.handle.net/10353/d1016068
- Description: Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.
- Full Text:
- Date Issued: 2014
Studies in the thiophenol mediated substitution and reductive dehalogenation of 3 bromoacetylcoumarins
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017