Manipulating Supramolecular Assembly in Water and Aqueous Mixtures

Tulane University, New Orleans LA

Investigators

Abstract

Deep cavity cavitands are container-shaped supramolecular complexes that contain a one-nanometer, rigid, non-polar binding pocket and a hydrophilic exterior coating that bestows good water solubility. Cavitands have proven useful "hosts" because of their ability to bind other molecules, or "guests", within their pockets and assemble in well-defined stoichiometries. They have applications in studies of protein solubility, in controlled release of pharmaceuticals, in separations, in the precise control of photochemical reactions, and as gelling agents. The fundamental understanding of these supramolecular complexes requires a molecular-level understanding of the interactions between hosts and guests in solution. A collaborative research project is proposed that combines molecular simulation and experimental studies aimed at investigating the impact of aqueous mixtures with co-solvent and polymeric additives on the forces driving cavitand assembly. The overarching goal of the proposed research is to develop molecular tools for controlling supramolecular cavitand assembly by manipulating the solvent properties that mediate host/guest interactions. The following topics will be studied: 1) How do alcoholic co-solvents moderate cavitand binding and assembly thermodynamics for a series of amphiphilic and non-polar guests? 2) How do changes in the hydrophobicity and hydrophilicity of the functional groups ringing the cavitand host pocket portals impact pocket hydration thermodynamics, drying/filling kinetics, and guest binding affinities? 3) What is the impact of water-soluble polymer crowding agents on the stability of moderately stable dimeric cavitand complexes? Molecular dynamics simulations of guest binding and cavitand complex formation will be performed over a range of solvent conditions and cavitand functions to examine water and alcohol structural correlations with host/guest complexes, complexation thermodynamics, wetting of host binding pockets, and osmotic stresses to gain molecular-scale insights into the forces stabilizing these assemblies. Complementary experiments will be performed to examine the effects of host functions and aqueous mixture compositions on the resulting cavitand complexes, using Nuclear Magnetic Resonance and light scattering, and the underlying assembly thermodynamics, using calorimetry. In addition to graduate and undergraduate student training, the proposed project will include an outreach program to the New Orleans Charter Science and Mathematics High School that serves a predominantly underrepresented minority student base. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.