The specific ion effects on macromolecular systems
Description
Ion specific effects are observed in a broad range of aqueous solutions. In particular, ion-specific effect in macromolecular systems are commonly known as the normal and reverse Hofmeister effects. This dissertation examines these Hofmeister effects in model examples and the protein ubiquitin, describing work to probe the thermodynamics of the non-covalent interactions behind these phenomena. Furthermore, how these ion specific effects can be utilized to control reactions in nano-spaces is also discussed. The direct interaction of anions with synthetic water-soluble molecules, including cyclodextrins and small-cavitands, has been proved to be useful models to study the thermodynamics of the interaction of anions with well-defined, non-polar pockets, and therefore to mimic the direct ionic interaction with more complicated macromolecules such as proteins. The effect of structure modification to the cyclodextrins and small-cavitands will be discussed. Ubiquitin is selected as the model protein to study the reverse Hofmeister effect and its mechanism. The effect on the changes in its biophysical properties, especially its aggregation and thermally induced unfolding, demonstrate that changes follow the reverse Hofmeister effect at low pH, and suggest that at higher pH normal, salting-in Hofmeister effects are manifest. The mechanism of these processes is explored with the HSQC NMR titrations to detect anion binding to specific points on the ubiquitin surface. Binding affinities were determined. The strong correlation of the binding affinity with the observation of the biophysical properties, including the aggregation and thermally induced unfolding, suggests that the reverse Hofmeister effect is directly driven by the anion specific interactions to preferred binding sites on the protein surface. The encapsulation and reactivity of an α,ω-amino halide guest within two supramolecular containers has been characterized. The NMR spectroscopy results suggest these long-chain guests adopt J-shaped conformation or motifs in the dimeric nano-capsule space. The kinetics of the macrocyclization reaction of this guest, was explored in the presence of different salts. Both anion and cation effects show the reaction rate is modulated by the ions in solution and follow the Hofmeister effect.