Use of Secondary Sphere Hydrogen Bonds for Stabilization and Divergent Reactivity in Transition Metal Complexes

Abstract

This dissertation describes advances made in the synthesis and reactivity of first row transition metal complexes featuring ligands with secondary sphere hydrogen bonding moieties. Inspiration for these complexes comes from biological systems, in which metalloenzymes incorporate outer sphere acidic residues for a variety of purposes, including substrate binding and stabilization of reactive intermediates. The difficulty of strategically modifying enzymes and characterization of the resulting species has led to the development of a wide array of synthetic complexes, with the intent of mimicking structures and reactivity observed in the related biological systems. Synthetic systems used to model biological active site reactivity and mechanism have more recently been modified with the addition of secondary sphere acidic residues to better mimic enzyme active sites. In enzymes, such acidic residues are naturally stable even in reducing environments, however, this can present synthetic challenges in model systems. Additionally, while secondary coordination sphere acidic residues can help in the capture and stabilization of elusive and reactive intermediates, observing these intermediates in synthetic model systems remains difficult. With these challenges in minds, we synthesized a series of nickel, iron, and copper complexes with a neutral ligand that features three hydrogen bond donor groups in the secondary coordination sphere. We set out to demonstrate that the secondary sphere hydrogen bonds would enable us to stabilize highly reactive complexes and capture intermediates along small molecule activation pathways. With a set of nickel(II) complexes, we found that the compounds are stable in the presence of strong reductants, allowing us to isolate and characterize a rare nickel(I) complex with hydrogen bonds. This species showed enhanced stability and selective reactivity for fluoride abstraction that a related complex without hydrogen bonds did not. In another study, we used the same ligand to stabilize a high-valent intermediate of dioxygen activation using an iron(II) precursor. On the same timescale, no dioxygen activation was observed when using ligands without hydrogen bonds, indicating they may play a role in stabilizing of the intermediates and products of the oxygen reduction reaction. Finally, a series of copper(I) complexes were synthesized using several ligand variants with varying hydrogen bond donor strength. Capture and reduction of nitrite by these copper(I) complexes was observed, and hydrogen bond donor strength was shown to affect the stability of the complex. Reactions of analogous, stable copper(I) fluoride complexes with a nitrite source resulted in immediate reduction of nitrite, indicating the mechanism of reduction may be dependent on the binding of nitrite to the complex with hydrogen bonds. Together, these studies demonstrate how small molecule activation may be enabled by the presence of secondary sphere hydrogen bonds, which can stabilize reactive intermediates and/or their products, as observed in metalloenzymes.