DNA bases in crystal engineering

Hoxha, Kreshnik

Chemistry
November 2014

Thesis or dissertation


Rights
© 2014 Kreshnik Hoxha. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

The work described in this thesis focuses on understanding the solid state interactions of organic molecules such as DNA nucleobases using established principles from crystal engineering and the synthon theory. Studying the intermolecular interactions is an indispensable tool to the crystal engineer when it comes to identifying functional groups which generate synthons that govern molecular recognition and self-assembly.

Chapter 3 focuses on the growth and design of single crystal materials of DNA bases and their carboxylic acid derivatives with various other molecules. The aim of the chapter was to probe the hydrogen bonding displayed by these systems. The challenges associated with dissolving the nucleobases in organic and aqueous solvents prompted alternative synthetic route to mitigate solubility challenges. Altering the pH of the system was found useful in aiding dissolution. Such synthetic approach has led to the preparation of novel nucleobase salts of bis-guaninium sulphate in three different hydrate forms. The material obtained was a channel hydrate and it was possible to remove water partially and fully while retaining crystallinity. No structural collapse was observed upon full dehydration and the material obtained contained an empty channel hydrate. Co-crystallisation of cytosine with 1,10-phenanthroline is discussed in depth and the results are compared to crystal structure prediction results to rationalise co-crystal formation from an energetic perspective. Calculations on the energy landscape revealed that in the case of cytosine and 1,10-phenanthroline there is a favourable energetic driving force for co-crystallisation. This, however, does not apply to the co-crystallisation of the other DNA bases with 1,10-phenanthroline as these systems did not produce co-crystals and remained as mixtures of precursors. The chapter also describes structural features of thymine acetic acid, melaminium nitrilotriacetate trihydrate and co-crystals of caffeine with 2-nitroterepthalic acid. These structures are closely examined for their hydrogen bonding motifs.

Chapter 4 covers a wide range of coordination compounds which relate to hydrogen-bonded networks of DNA nucleobases and their carboxylic acid derivatives. These complex architectures contain both coordination bonds as well as intermolecular interactions in the form of hydrogen bonding and stacking interactions. Metal-dipicolinate complexes treated with adenine and cytosine afforded hydrogen-bonded networks where protonated DNA bases interacted with the ligand via hydrogen bonding. The chapter discusses the role of water molecules in acting as spacers and stabilising crystal structure, especially in cases where there is an imbalance of hydrogen bond donors and acceptors.

Orotic acid was heavily used owing to its chelating nature. This part of Chapter 4 focuses on novel crystal structures where orotic acid utilises its hydrogen bonding capability. An extensive discussion is provided on how the level of hydration impacts crystal packing and alters synthon formation. In addition, the chapter also focuses on the structural changes resulting from changing the position of the functional group in the ligands

Publisher
Department of Chemistry, The University of Hull
Supervisor
Prior, Timothy J.
Sponsor (Organisation)
University of Hull
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
15 MB
Identifier
hull:11660
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