Abstract
The design and preparation of strong and selective artificial receptors, especially biomi-metic receptors that function in aqueous solution, has proved truly challenging. In this thesis it will be described how the strengths of dynamic combinatorial chemistry can be used to great advantage in this field. The aim of this project has therefore been to develop new ways of using dynamic combinatorial libraries for molecular recognition in aqueous media. The focus has been on using what has been learned from the well-established di-sulfide exchange chemistry to incorporate a new reaction into dynamic combinatorial chemistry, namely the reversible diselenide exchange reaction.
The first part of the thesis describes the development of a thermally induced OAr → SeAr migration reaction. Here, it was proven possible to rearrange a variety of substituted O-aryl selenocarbamates into the corresponding Se-aryl selenocarbamates. This rear-rangement has enabled the preparation of aryl selenols from the corresponding phenols in three convenient steps and additionally, it was found how the rearrangement protocol worked well for a wide range of functional groups. The reaction mechanism of the rear-rangement was examined both experimentally and theoretically and found to be unique in organoselenium chemistry by proceeding through a four-membered cyclic transition state following first-order kinetics.
Subsequently, this thesis illustrates how an aliphatic diselenide could be used to catalyse the formation of a disulfide based dynamic combinatorial library under physiological pH in the μM regime. Under these conditions the disulfide exchange reaction is otherwise typ-ically too slow to be practical in dynamic combinatorial chemistry why the catalysis was an important improvement of the system. It was found that a catalyst loading of either 10 or 1.0 mol% diselenide was sufficient to catalyse the library formation while 0.1 mol% catalyst had little effect on the reaction.
Next, it was proven possible to introduce the diselenide exchange reaction as a reversible reaction for dynamic combinatorial chemistry in water at physiological pH. Primary stud-ies demonstrated how both aliphatic and aromatic diselenide based dynamic combinato-rial libraries equilibrated under thermodynamic control at neutral pH. Furthermore, it has proven possible to combine diselenide based libraries with thiols to give rather complex mixtures where disulfides, diselenides, and selenenylsulfides coexisted. Preliminary re-sults have moreover shown how it was possible to synthesise larger bis-diselenides, thereby giving the possibility of the presence of oligo-diselenide macrocycles or linear species in the dynamic combinatorial libraries.
The last part of the thesis shows how a triangular triple helicate has been prepared from Zn2+ and a threefold-symmetric trialdehyde subcomponent. The dynamic nature of the linkages holding the triple helicate together has allowed the creation of a simple system of assembled structures whose function was controlled by external stimuli. Through sub-component substitution, the triple helicate was found to transform into a double helicate, which had the ability to adapt its conformation in the presence of planar aromatic guest molecules. It was found that the double helicate could form 1:1 complexes with a range of aromatic guest molecules and the binding to these were examined.
The first part of the thesis describes the development of a thermally induced OAr → SeAr migration reaction. Here, it was proven possible to rearrange a variety of substituted O-aryl selenocarbamates into the corresponding Se-aryl selenocarbamates. This rear-rangement has enabled the preparation of aryl selenols from the corresponding phenols in three convenient steps and additionally, it was found how the rearrangement protocol worked well for a wide range of functional groups. The reaction mechanism of the rear-rangement was examined both experimentally and theoretically and found to be unique in organoselenium chemistry by proceeding through a four-membered cyclic transition state following first-order kinetics.
Subsequently, this thesis illustrates how an aliphatic diselenide could be used to catalyse the formation of a disulfide based dynamic combinatorial library under physiological pH in the μM regime. Under these conditions the disulfide exchange reaction is otherwise typ-ically too slow to be practical in dynamic combinatorial chemistry why the catalysis was an important improvement of the system. It was found that a catalyst loading of either 10 or 1.0 mol% diselenide was sufficient to catalyse the library formation while 0.1 mol% catalyst had little effect on the reaction.
Next, it was proven possible to introduce the diselenide exchange reaction as a reversible reaction for dynamic combinatorial chemistry in water at physiological pH. Primary stud-ies demonstrated how both aliphatic and aromatic diselenide based dynamic combinato-rial libraries equilibrated under thermodynamic control at neutral pH. Furthermore, it has proven possible to combine diselenide based libraries with thiols to give rather complex mixtures where disulfides, diselenides, and selenenylsulfides coexisted. Preliminary re-sults have moreover shown how it was possible to synthesise larger bis-diselenides, thereby giving the possibility of the presence of oligo-diselenide macrocycles or linear species in the dynamic combinatorial libraries.
The last part of the thesis shows how a triangular triple helicate has been prepared from Zn2+ and a threefold-symmetric trialdehyde subcomponent. The dynamic nature of the linkages holding the triple helicate together has allowed the creation of a simple system of assembled structures whose function was controlled by external stimuli. Through sub-component substitution, the triple helicate was found to transform into a double helicate, which had the ability to adapt its conformation in the presence of planar aromatic guest molecules. It was found that the double helicate could form 1:1 complexes with a range of aromatic guest molecules and the binding to these were examined.
| Originalsprog | Engelsk |
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| Forlag | Department of Chemistry, Faculty of Science, University of Copenhagen |
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| Antal sider | 172 |
| ISBN (Trykt) | 978-87-91963-36-0 |
| Status | Udgivet - 2013 |