UC Irvine

In biological systems, metalloproteins have evolved to carry out difficult chemical transformations with high activity and selectivity through control of the primary and secondary coordination spheres. Inorganic chemists have developed organic ligand scaffolds to prepare small-molecule model complexes with similar coordination environments to active sites of metalloproteins. However, the resulting complexes are often unable to carry out the same reactivity as their metalloprotein counterparts because they lack the precise control of the secondary coordination sphere.

The most common secondary coordination sphere interaction in metalloproteins is hydrogen bonds (H-bonds). Our group has shown that intramolecular H-bonds can be incorporated into rigid ligand scaffolds to facilitate the activation of small molecules. This has been demonstrated through the use of tetradentate, anionic, and C3 symmetric ligand scaffolds, which when bound to a metal ion have one open coordination site available for binding of small molecules. Intramolecular H-bonds have been incorporated through the introduction of sulfonamido, urea and amido groups, which can serve as H-bond donors or acceptors. This dissertation focuses on ligand design that systematically changes the H-bonding network in the secondary coordination sphere around M‒O and M‒OH units.

The first study investigates the effect of having intramolecular H-bond donors and acceptors in the same ligand by developing new ligands based upon the symmetrical sulfonamido tripodal ligand [MST]3‒ and the symmetrical urea tripodal ligand [H3buea]3‒. Two new hybrid ligand systems ([H1tol]3‒ and [H22tol]3‒) having varying numbers of urea and sulfonamido groups were synthesized. These four ligands were used to synthesize a series of CoII/III‒OH complexes with varying numbers of intramolecular H-bonds. These complexes allowed for the study of the structural and physical properties arising from modification of the H-bonding network about a Co‒OH unit.

The remainder of the dissertation focuses on the development of new hybrid urea tripodal ligands ([H33R]3‒) based upon [H3buea]3‒. These ligands were developed to maintain a constant primary coordination sphere, while modifying the properties of only one H-bond donor. This is accomplished through attaching a substituted phenyl ring with electron-withdrawing groups on only one of the urea units, which modulates the acidity of this urea NH. These ligands were used to synthesize a series of M‒O(H) (M = MnIII/IV/V and FeIII) complexes, which showed that their properties are highly dependent on changes to only one H-bond.