Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597989
Title: Dynamic combinatorial libraries in theory and practice
Author: Corbett, P. T.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Abstract:
Dynamic Combinatorial Chemistry is a technique for the discovery of new host and guest compounds, which may potentially be developed into catalysts, sensors, medicines and other useful substances. In this thesis, experimental and theoretical studies will be presented that explore the behaviour of dynamic combinatorial libraries, providing a greater understanding of the reliability and generality of the technique. Chapter 1 introduces dynamic combinatorial chemistry. Its context of molecular recognition and host-guest chemistry is examined, and a selection of approaches to the problem of host and guest design and synthesis are examined. A review of dynamic combinatorial chemistry is conducted, starting with the earliest proof-of-principle systems. Finally, the use of thiol-disulfide exchange in dynamic combinatorial chemistry (a major theme of this thesis) is reviewed. Chapter 2 describes an extension of a previously published dynamic combinatorial library system, using several new templates, and improved analytical techniques. The amplification of Macrocyclic disulfides by the templates is examined, and compared with binding constant obtained by ITC in order to study the relationship between these quantities. Chapter 3 examines a previously-unknown receptor that was isolated from the above system. Its amplification using a range of templates is explored, and its powerful, induced-fit binding is studied. Chapter 4 describes a wider society of DCLs based on Macrocyclic disulfides. Several different building blocks are used to generate many different DCLs, to explore the factors involved in the design of building blocks, and the nature of the library members amplified. Having examined these, large DCLs containing up to seven different building blocks are examined, in order to assess the applicability of dynamic combinatorial chemistry to highly diverse libraries. Chapter 5 concerns a number of conceptual and mathematical models of dynamic combinatorial chemistry. The available literature is surveyed and assessed, and the computer program DCLSim is described. DCLSim is then used to develop two further model systems, to extend and clarify previous work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597989  DOI: Not available
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