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

Khalili, Pegah

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

Master Thesis

2013

Publisher

University of Cape Town

Department

Department of Chemistry

Faculty

Faculty of Science

Abstract

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.

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