Generation of a virtual library of terpenes using graph theory, and its application in exploration of the mechanisms of terpene biosynthesis
- Authors: Dendera, Washington
- Date: 2020
- Subjects: Terpenes , Plants -- Metabolism , Computational biology , Bioinformatics , Organic compounds -- Synthesis , Monoterpenes , Molecular biology -- Computer simulation
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123453 , vital:35439
- Description: Terpenes form a large group of organic compounds which have proven to be of use to many living organisms being used by plants for metabolism (Pichersky and Gershenzon, 1934; McGarvey and Croteau, 1995; Gershenzon and Dudareva, 2007), defence or as a means to attract pollinators and also used by humans in medical, pharmaceutical and food industry (Bicas, Dionísio and Pastore, 2009; Marmulla and Harder, 2014; Kandi et al., 2015). Following on literature methods to generate chemical libraries using graph theoretic techniques, complete libraries of all possible terpene isomers have been constructed with the goal of construction of derivative libraries of possible carbocation intermediates which are important in the elucidation of mechanisms in the biosynthesis of terpenes. Virtual library generation of monoterpenes was first achieved by generating graphs of order 7, 8, 9 and 10 using the Nauty and Traces suite. These were screened and processed with a set of collated Python scripts written to recognize the graphs in text format and translate them to molecules, minimizing through Tinker whilst discarding graphs that violate chemistry laws. As a result of the computational time required only order 7 and order 10 graphs were processed. Out of the 873 graphs generated from order seven, 353 were converted to molecules and from the 11,7 million produced from order 10 half were processed resulting in the production of 442928 compounds (repeats included). For screening, 55 366 compounds were docked in the active site of limonene synthase; of these 2355 ligands had a good Vina docking score with a binding energy of between -7.0 and -7.4 kcal.mol-1. When these best docked molecules were overlaid in the active site a map of possible ligand positions within the active site of limonene synthase was traced out.
- Full Text:
- Date Issued: 2020
- Authors: Dendera, Washington
- Date: 2020
- Subjects: Terpenes , Plants -- Metabolism , Computational biology , Bioinformatics , Organic compounds -- Synthesis , Monoterpenes , Molecular biology -- Computer simulation
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123453 , vital:35439
- Description: Terpenes form a large group of organic compounds which have proven to be of use to many living organisms being used by plants for metabolism (Pichersky and Gershenzon, 1934; McGarvey and Croteau, 1995; Gershenzon and Dudareva, 2007), defence or as a means to attract pollinators and also used by humans in medical, pharmaceutical and food industry (Bicas, Dionísio and Pastore, 2009; Marmulla and Harder, 2014; Kandi et al., 2015). Following on literature methods to generate chemical libraries using graph theoretic techniques, complete libraries of all possible terpene isomers have been constructed with the goal of construction of derivative libraries of possible carbocation intermediates which are important in the elucidation of mechanisms in the biosynthesis of terpenes. Virtual library generation of monoterpenes was first achieved by generating graphs of order 7, 8, 9 and 10 using the Nauty and Traces suite. These were screened and processed with a set of collated Python scripts written to recognize the graphs in text format and translate them to molecules, minimizing through Tinker whilst discarding graphs that violate chemistry laws. As a result of the computational time required only order 7 and order 10 graphs were processed. Out of the 873 graphs generated from order seven, 353 were converted to molecules and from the 11,7 million produced from order 10 half were processed resulting in the production of 442928 compounds (repeats included). For screening, 55 366 compounds were docked in the active site of limonene synthase; of these 2355 ligands had a good Vina docking score with a binding energy of between -7.0 and -7.4 kcal.mol-1. When these best docked molecules were overlaid in the active site a map of possible ligand positions within the active site of limonene synthase was traced out.
- Full Text:
- Date Issued: 2020
The characterization and application of novel xanthenyland thioxanthenyl-derived compounds as hosts in the presence of various applicable guest mixtures
- Authors: Jooste, Daniel Victor
- Date: 2020
- Subjects: Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/49104 , vital:41601
- Description: In this work, the host potential of four novel, structurally-related compounds, trans- N,N’-bis(9-phenyl-9-xanthenyl)cyclohexane-1,2-diamine (1,2-DAX), trans-N,N’-bis(9- phenyl-9-thioxanthenyl)cyclohexane-1,2-diamine (1,2-DAT), trans-N,N’-bis(9-phenyl- 9-xanthenyl)cyclohexane-1,4-diamine (1,4-DAX), and trans-N,N’-bis(9-phenyl-9- thioxanthenyl)cyclohexane-1,4-diamine (1,4-DAT), were investigated for their possible employment in the separation of isomers and other related compounds using host– guest chemistry. These hosts were synthesized following a Grignard reaction with phenylmagnesium bromide on either xanthone or thioxanthone. The resultant alcohol was treated with perchloric acid, before finally being linked with either trans-1,2- or trans-1,4-diaminocyclohexane to afford the four title host compounds. Initially, the feasibility of these hosts for separating isomers and related compounds was investigated by recrystallizing each one independently from various guest compounds including the methylpyridines and pyridine, xylenes and ethylbenzene, heterocyclic six-membered ring compounds, aniline, N-methylaniline and N,Ndimethylaniline, and also the alkylbenzenes toluene, cumene and ethylbenzene. 1HNMR spectroscopy was used to ascertain if inclusion of the guest species had occurred in this manner and, if so, the host:guest ratio of the complex. Guest–guest competitions were subsequently conducted in order to establish the selectivity of the hosts when presented with a mixture of guests, and if the host would be able to discriminate between them. Gas chromatography-mass spectrometry (GC-MS) was the analytical method of choice here if 1H-NMR spectroscopy was not suitable owing to guest–guest signal overlap. Here, the host was recrystallized from binary, ternary and quaternary mixed guests, where each was present in equimolar amounts. Additionally, binary competition experiments were conducted in mixed guest solvents where the molar ratios of the guests were varied, and host selectivity for these guests evaluated visually by means of selectivity profiles. Single crystal X-ray diffraction (SC-XRD) and thermal analysis were performed on any complexes that afforded crystals of suitable quality in order to relate inherent host–guest interactions and thermal stability to the observed host selectivity from the competition experiments. The more prevalent interactions that were evident in these inclusion complexes between host and guest species were, more usually, and interactions, as well as other short contacts. Hydrogen bonding interactions were observed in only a few of the complexes. Guest accommodation type was also investigated, and these species resided in either discrete cavities or channels within the host crystal, depending on the guest. For the most part, traces obtained from thermal analyses were highly convoluted and difficult to interpret. As a result, guest release onset temperatures could not be determined for all of the inclusion complexes. In some cases, however, this temperature was successfully measured and correlated directly with the observed selectivity order of the host suggested by the competition experiments. Both enhanced and contrasting results were obtained for the four host compounds. In all cases, 1,2-DAX and 1,2-DAT successfully formed complexes with each of the guest species from each series. Interestingly, the 1,4-derived hosts, however, were more selective in that 1,4-DAX did not complex with only one of the guest solvents, while 1,4-DAT did not enclathrate as many as ten of these solvents. The competition investigations showed that, in most of these experiments, the host compounds displayed selectivity for one of the guests present in the mixture, and in some cases, this selectivity was pronounced, alluding to the feasibility of separating related guests from one another through host–guest chemistry principles. Computational calculations were, additionally, conducted on each of the host molecules in order to gain a better understanding of their geometries, and to compare these with the apohost crystal structures. Significant geometry differences were noted between the calculated and crystal structures.
- Full Text:
- Date Issued: 2020
- Authors: Jooste, Daniel Victor
- Date: 2020
- Subjects: Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/49104 , vital:41601
- Description: In this work, the host potential of four novel, structurally-related compounds, trans- N,N’-bis(9-phenyl-9-xanthenyl)cyclohexane-1,2-diamine (1,2-DAX), trans-N,N’-bis(9- phenyl-9-thioxanthenyl)cyclohexane-1,2-diamine (1,2-DAT), trans-N,N’-bis(9-phenyl- 9-xanthenyl)cyclohexane-1,4-diamine (1,4-DAX), and trans-N,N’-bis(9-phenyl-9- thioxanthenyl)cyclohexane-1,4-diamine (1,4-DAT), were investigated for their possible employment in the separation of isomers and other related compounds using host– guest chemistry. These hosts were synthesized following a Grignard reaction with phenylmagnesium bromide on either xanthone or thioxanthone. The resultant alcohol was treated with perchloric acid, before finally being linked with either trans-1,2- or trans-1,4-diaminocyclohexane to afford the four title host compounds. Initially, the feasibility of these hosts for separating isomers and related compounds was investigated by recrystallizing each one independently from various guest compounds including the methylpyridines and pyridine, xylenes and ethylbenzene, heterocyclic six-membered ring compounds, aniline, N-methylaniline and N,Ndimethylaniline, and also the alkylbenzenes toluene, cumene and ethylbenzene. 1HNMR spectroscopy was used to ascertain if inclusion of the guest species had occurred in this manner and, if so, the host:guest ratio of the complex. Guest–guest competitions were subsequently conducted in order to establish the selectivity of the hosts when presented with a mixture of guests, and if the host would be able to discriminate between them. Gas chromatography-mass spectrometry (GC-MS) was the analytical method of choice here if 1H-NMR spectroscopy was not suitable owing to guest–guest signal overlap. Here, the host was recrystallized from binary, ternary and quaternary mixed guests, where each was present in equimolar amounts. Additionally, binary competition experiments were conducted in mixed guest solvents where the molar ratios of the guests were varied, and host selectivity for these guests evaluated visually by means of selectivity profiles. Single crystal X-ray diffraction (SC-XRD) and thermal analysis were performed on any complexes that afforded crystals of suitable quality in order to relate inherent host–guest interactions and thermal stability to the observed host selectivity from the competition experiments. The more prevalent interactions that were evident in these inclusion complexes between host and guest species were, more usually, and interactions, as well as other short contacts. Hydrogen bonding interactions were observed in only a few of the complexes. Guest accommodation type was also investigated, and these species resided in either discrete cavities or channels within the host crystal, depending on the guest. For the most part, traces obtained from thermal analyses were highly convoluted and difficult to interpret. As a result, guest release onset temperatures could not be determined for all of the inclusion complexes. In some cases, however, this temperature was successfully measured and correlated directly with the observed selectivity order of the host suggested by the competition experiments. Both enhanced and contrasting results were obtained for the four host compounds. In all cases, 1,2-DAX and 1,2-DAT successfully formed complexes with each of the guest species from each series. Interestingly, the 1,4-derived hosts, however, were more selective in that 1,4-DAX did not complex with only one of the guest solvents, while 1,4-DAT did not enclathrate as many as ten of these solvents. The competition investigations showed that, in most of these experiments, the host compounds displayed selectivity for one of the guests present in the mixture, and in some cases, this selectivity was pronounced, alluding to the feasibility of separating related guests from one another through host–guest chemistry principles. Computational calculations were, additionally, conducted on each of the host molecules in order to gain a better understanding of their geometries, and to compare these with the apohost crystal structures. Significant geometry differences were noted between the calculated and crystal structures.
- Full Text:
- Date Issued: 2020
- «
- ‹
- 1
- ›
- »