acase@tulane.edu / Rational, synthetic design is implemented in a systematic study of the effect of host shape and properties and manifestations of the reverse Hofmeister effect. Hofmeister specific effects were observed at the molecular level wherein it was shown that key to the effectiveness of some “salting-in” anions is their complementarity to hydrophobic cavities and other binding surfaces. A gamut of responses was observed across a range of hosts possessing different structural and functional motifs. These observations were typically manifest at a relatively low (<20 mM) critical precipitation concentration (CPC). Furthermore, it was shown that at low concentrations, typical observations of screening effects are not observed, and binding-site competition is a predominant factor when multiple anions are present in solution. In terms of quantifying the ion recognition sites of different, similarly charged hosts there is little difference in anion affinity, but large differences are observed in 1/CPC values. Thus, subtle changes in the recognition site have dramatic changes in terms of manifestations of the reverse Hofmeister effect. This is (to the authors best knowledge) the first example of a systematic study sequentially modifying small molecular hosts and utilizing them to study reverse Hofmeister trends. In total 12 hosts and 6 host-guest complexes were examined. These studies demonstrate applications of the reverse Hofmeister effect to generate single crystal X-ray structures, with potential applications in protein and small molecule purifications, separations, and crystallizations. / 1 / Jacobs Jordan

archives@tulane.edu / Solubility is the ability of a molecule to favorably interact with a solvent. While seemingly simple in application many phenomena arise from knife-edge like conditions between solubility and insolubility. Herein, three of these phenomena; co-non-solvency, the hydrophobic effect, and the direct and reverse Hofmeister effects are investigated in detail to parse out a mechanistic view of solubility in each case. The first phenomenon, co-non-solvency, is the insolubility of a thermo-responsive polymer and a mixture of two good cosolvents. Host-guest systems are used to probe small molecule interactions in the presence of cosolvents for co-non-solvent effects. The second phenomenon, the hydrophobic effect, is often colloquially described as “oil and water do not mix.” However, this is much more complex when diving into the energetic contributions. Host-guest systems are used to determine structural effects novel hosts and guests have on the hydrophobic effect in collaboration with the computational community. The third phenomenon, the Hofmeister effects, are explored through the fine tuning of solubility of lysozyme through the addition of sodium perchlorate in varying pHs. This is used to determine a mechanistic view of protein solubility in the presence of salts. / 1 / Nicholas Ernst

No description available.

Doctor of Philosophy / Department of Physics / Jeremy D. Schmit / Diseases such as Alzheimer’s, Parkinson’s, eye lens cataracts, and Type 2 diabetes are the results of protein aggregation. Protein aggregation is also a problem in pharmaceutical industry for designing protein based drugs for long term stability. Disordered states such as precipitates and gels and ordered states such as crystals, micro tubules and capsids are both possible outcomes of protein–protein interaction. To understand the outcomes of protein–protein interaction and to find the ways to control forces, it is required to study both kinetic and equilibrium factors in protein–protein interactions. Salting in/salting out and Hofmeister effects are familiar terminologies used in protein science field from more than a century to represent the effects of salt on protein solubility, but they are yet to be understood theoretically. Here, we build a theory accounting both attractive and repulsive electrostatic interactions via the Poisson Boltzmann equation, ion–protein binding via grand cannonical partition function and implicit ion–water interaction using hydrated ion size, for describing salting in/salting out phenomena and Hofmeister and/or salt specific effect. Our model free energy includes Coulomb energy, salt entropy and ion–protein binding free energy. We find that the salting in behavior seen at low salt concentration near the isoelectric point of the protein is the output of Coulomb energy such that the addition of salt not only screens dipole attraction but also it enhances the monopole repulsion due to anion binding. The salting out behavior appearing after salting in at high salt concentration is due to a salt mediated depletion interaction. We also find that the salting out seen far from the isoelectric point of the protein is dominated by the salt entropy term. At low salt, the dominant effect comes from the entropic cost of confining ions within the aggregates and at high salt, the dominant effect comes from the entropy gain by ions in solution by enhancing the depletion attraction. The ion size has significant effects on the entropic term which leads to the salt specificity in the protein solubility. Crystal growth of anisotropic and fragile molecules such as proteins is a challenging task because kinetics search for a molecule having the correct binding state from a large ensemble of molecules. In the search process, crystal growth might suffer from a kinetic trap called self–poisoning. Here, we use Monte Carlo simulation to show why protein crystallization is vulnerable to the poisoning and how one can avoid such trap or recover crystal growth from such trap during crystallization. We show that self–poisoning requires only three minimal ingredients and these are related to the binding affinity of a protein molecule and its probability of occurrence. If a molecule attaches to the crystal in the crystallographic state then its binding energy will be high but in protein system this happens with very low probability (≈ 10−5). On the other hand, non–crystallographic binding is energetically weak, but it is highly probable to happen. If these things are realized, then it will not be surprising to encounter with self–poisoning during protein crystallization. The only way to recover or avoid poisoning is to alter the solution condition slightly such as by changing temperature or salt concentration or protein concentration etc.