Probes for the investigation of weak interactions in ligand-receptor binding events

The focus of this thesis is the development of probes for weak interactions of ligand-receptor pairs. The design, synthesis, and characterization of two redox-active, solvatochromic probes for ligand-receptor binding are presented. The effect of solvent environment on the electrochemical and spectroscopic properties of biotinylated and desthiobiotinylated iron (II) tetracyanobipyridine complexes, [Fe(BMB)(CN)4]2- and [Fe(DMB)(CN) 4]2-, is explored and results show shifts potential and absorption peaks that are linearly dependent on solvent acceptor number. These complexes are highly sensitive to changes in solvent environment, making them very good candidates to probe energetics of ligand receptor binding.;In its entirety, this thesis presents a series of redox-active probes that are highly sensitive to the surrounding environment. It has been demonstrated that a change in the binding constant of the probe results in small changes in second-sphere coordination by the protein that in turn affect the electrochemical and optical properties of the compounds. The three-dimensional structure of [Fe(BMB)(CN)4]2- bound to avidin shows the probe partially buried in a hydrophobic pocket with a direct interaction between the protein and the transition metal complex. Molecular dynamic simulations suggest that differences in protein structure are responsible for the difference in physical properties of the probes when bound to avidin. Additionally, when avidin binds to one of the probes, the reorganization energy increases and the rate of electron transfer decreases consistent with expected values for a redox-active center moving from a high dielectric medium to a low dielectric medium.;These studies further the understanding of how a protein environment affects the physical properties of small molecules. The versatility and sensitivity of [Fe(bpy)(CN)4]2- complexes to small changes in binding affinities could result in their use as probes for understanding individual components of ligand-receptor binding energetics.