Developing a triangular tessellation method for the analysis of medium ring pucker conformations

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dc.contributor.advisorNaidoo, Kevin Jen_ZA
dc.contributor.authorKhalili, Pegahen_ZA
dc.date.accessioned2014-08-20T19:27:37Z
dc.date.available2014-08-20T19:27:37Z
dc.date.issued2013en_ZA
dc.description.abstractThe main focus of this thesis is to investigate the relative conformational flexibilities of α-, β- and γ-cyclodextrins in water by analysing their macrocyclic ring puckering motion from Molecular Dynamics (MD) simulations. In particular, the puckering of the CDs is investigated through a coarse grained analysis of full atomistic simulations, where the CD conformational motions are studied on the macrocyclic scale rather than the atomistic scale. The flexibilities of the cyclodextrins (CDs) are then compared to their experimentally-observed aqueous solubility trend in order to try explain the anomalously flow solubility of β-cyclodextrin. β-CD has important applications in industry, such as the pharmaceutical industry, thus exploring the conformational reasons for its low solubility can help to design more effective cyclodextrin-based products in future. The ring puckering of the CDs is measured quantitatively using a reduced system of puckering coordinates based on the method of triangular tessellation. The triangular tessellation definition for monocylic 6-membered rings is first extended to 7- and 8-membered rings, and the corresponding puckering coordinates are derived mathematically. The macrocyclic CD rings are then simplified to monocyclic representations through an appropriate coarse graining of the molecules (specifically, α-, β- and γ-cyclodextrins are simplified to 6-, 7- and 8-sided rings, respectively), and the corresponding triangular tessellation definition is then used to measure their macrocyclic puckering. The rates of decay of the puckering motion are then calculated using time correlation functions, from which the relative flexibilities of the CDs is determined. Probability distributions are also used to investigate the ranges of the CD puckering. In addition, the horizontal contraction and expansion of the macrocyclic rings (termed """"breathing"""" herein) is analysed to supplement the puckering analysis. Puckering coordinates based on the triangular tessellation of 6-membered rings have been used previously to characterise all 38 canonical states of cyclohexane. In this thesis, a systematic procedure is developed to generate the triangular tessellation puckering coordinates of all the canonical states of 6-, 7- and 8-membered rings, and the coordinates for all canonical states of cycloheptane and cyclooctane are subsequently generated. These puckering coordinates can be useful not only in the conformational analysis of cyclohexane, cycloheptane and cyclooctane, but also to quantitatively characterise the conformations of 6-, 7- and 8-membered rings in general, both from experimental and computational studies.en_ZA
dc.identifier.apacitationKhalili, P. (2013). <i>Developing a triangular tessellation method for the analysis of medium ring pucker conformations</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6636en_ZA
dc.identifier.chicagocitationKhalili, Pegah. <i>"Developing a triangular tessellation method for the analysis of medium ring pucker conformations."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2013. http://hdl.handle.net/11427/6636en_ZA
dc.identifier.citationKhalili, P. 2013. Developing a triangular tessellation method for the analysis of medium ring pucker conformations. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Khalili, Pegah AB - The main focus of this thesis is to investigate the relative conformational flexibilities of α-, β- and γ-cyclodextrins in water by analysing their macrocyclic ring puckering motion from Molecular Dynamics (MD) simulations. In particular, the puckering of the CDs is investigated through a coarse grained analysis of full atomistic simulations, where the CD conformational motions are studied on the macrocyclic scale rather than the atomistic scale. The flexibilities of the cyclodextrins (CDs) are then compared to their experimentally-observed aqueous solubility trend in order to try explain the anomalously flow solubility of β-cyclodextrin. β-CD has important applications in industry, such as the pharmaceutical industry, thus exploring the conformational reasons for its low solubility can help to design more effective cyclodextrin-based products in future. The ring puckering of the CDs is measured quantitatively using a reduced system of puckering coordinates based on the method of triangular tessellation. The triangular tessellation definition for monocylic 6-membered rings is first extended to 7- and 8-membered rings, and the corresponding puckering coordinates are derived mathematically. The macrocyclic CD rings are then simplified to monocyclic representations through an appropriate coarse graining of the molecules (specifically, α-, β- and γ-cyclodextrins are simplified to 6-, 7- and 8-sided rings, respectively), and the corresponding triangular tessellation definition is then used to measure their macrocyclic puckering. The rates of decay of the puckering motion are then calculated using time correlation functions, from which the relative flexibilities of the CDs is determined. Probability distributions are also used to investigate the ranges of the CD puckering. In addition, the horizontal contraction and expansion of the macrocyclic rings (termed """"breathing"""" herein) is analysed to supplement the puckering analysis. Puckering coordinates based on the triangular tessellation of 6-membered rings have been used previously to characterise all 38 canonical states of cyclohexane. In this thesis, a systematic procedure is developed to generate the triangular tessellation puckering coordinates of all the canonical states of 6-, 7- and 8-membered rings, and the coordinates for all canonical states of cycloheptane and cyclooctane are subsequently generated. These puckering coordinates can be useful not only in the conformational analysis of cyclohexane, cycloheptane and cyclooctane, but also to quantitatively characterise the conformations of 6-, 7- and 8-membered rings in general, both from experimental and computational studies. DA - 2013 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Developing a triangular tessellation method for the analysis of medium ring pucker conformations TI - Developing a triangular tessellation method for the analysis of medium ring pucker conformations UR - http://hdl.handle.net/11427/6636 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6636
dc.identifier.vancouvercitationKhalili P. Developing a triangular tessellation method for the analysis of medium ring pucker conformations. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2013 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6636en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.titleDeveloping a triangular tessellation method for the analysis of medium ring pucker conformationsen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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