Nature performs challenging chemical transformations with the help of metalloenzymes. The efficiency and selectivity of such reactions has been attributed to the control of the covalent as well as non-covalent interactions around the metal center. In synthetic systems, it has been difficult to emulate the long range non-covalent interactions that are found in native enzymes. To incorporate such non-covalent interactions into the modeling of the active sites of metalloenzymes, biotin-streptavidin (Sav) technology has been utilized to immobilize metal complexes within the protein scaffold. This dissertation describes my efforts in engineering artificial metalloproteins (ArMs) using biotin-Sav technology to install non-heme iron active sites that are capable of binding to small molecules. Chapter 2 describes the structural characterization of an FeII ArM that binds to nitric oxide to form Fe-nitrosyl species that has been characterized by electronic absorption, electron paramagnetic resonance, and Mössbauer spectroscopy as well as by X-ray crystallography. Chapter 3 describes the challenges that lability of Fe ions posed in our attempts to study dioxygen activation in a FeII ArM. A previously reported structure of the FeII ArM was re-refined with a new model that fits the electron density better. Addition of the substrate, phenylglyoxylic acid (PGA), to the FeII ArM led to leaching of the Fe ions from the ArM. The leaching of the Fe ions from the ArM was monitored spectroscopically by electronic absorption and Mössbauer spectroscopy. Chapter 4 describes the design and characterization of a μ-oxo-di-FeIII center within Sav. The μ-oxo-di-FeIII center was characterized spectroscopically as well as structurally by X-ray crystallography. The FeIIIFeIII center is capable of binding to external ligands like acetate and azide ions. Oxidation and reduction of the μ-oxo-di-FeIII center has also been studied by solution spectroscopy.

In nature, metalloproteins have evolved a precise control over the primary and secondary coordination sphere of their active sites to perform chemical transformations with high selectivity and efficiency. The approach developed in the Borovik lab to emulate these properties has been to synthesize molecular constructs that are capable of stabilizing reactive species through control of the primary coordination sphere of a metal ion with a rigid ligand platform and the secondary coordination sphere through hydrogen-bonding (H-bonding) interactions. This thesis describes how modifications of the secondary coordination sphere by incorporating both H-bond acceptors and donors affects the chemistry of metal complexes. Chapter 2 describes the protonation and oxidation of the previously reported [FeIVH3buea(O)]– complex. Addition of either a proton or oxidant to the FeIV-oxido complex resulted in the formation of a new FeIV species, characterized as the protonated congener of [FeIVH3buea(O)]–. Density functional theory (DFT) calculations and X-ray absorption spectroscopy (XAS) provided insight into the structural properties of the complex and suggested that the [H3buea]3– was the site of protonation, resulting in a tautomerization with the additional proton being H-bonded to the oxido ligand. These results demonstrated the difficulty in preparing high valent FeIV-hydroxido species. Chapter 3 explores the proton-coupled electron transfer (PCET) process for the oxidation of an FeIII-hydroxido complex to generate the corresponding FeIV-oxido complex. It was shown that the choice of solvent greatly affected the yield of the FeIV-oxido complex and that the decreased yield could be attributed to loss of the starting FeIII-hydroxido complex by acting as a base in the reaction. Chapter 4 explores how modifications of the secondary coordination sphere of a metal complex via replacement of one H-bond donor with an acceptor affected the stability of high valent Fe complexes. The [H2bupa]3– ligand incorporates an H-bond accepting group, an anionic amidate, within the secondary coordination sphere, which produced a unique “hybrid” FeIII-oxido/hydroxido complex with a proton likely positioned between the amidate nitrogen and oxido ligand. When oxidized to the FeIV oxidation state, the complex is best characterized as an FeIV-oxido complex with the proton positioned on the ligand.

The last two chapters examine the effect of group 2 and 3 metal ions on high valent Mn-oxido complexes. Chapter 5 describes the alteration of the redox properties of a series of Mn-oxido complexes within the [H3buea]3– ligand by the addition of CaII, SrII, or ScIII ions. Addition of these Lewis acidic metal ions to a MnV-oxido complex resulted in spontaneous electron transfer to [FeCp2] to generate the analogous MnIV-oxido Lewis acid adduct. The MnIV adduct could be independently generated by the addition of Lewis acids to the MnIV-oxido complex. Of the metal ions examined, addition of ScIII ions showed the greatest attenuation of the redox potential of the Mn-oxido complexes. Chapter 6 describes efforts to identify a putative MnIII-peroxido species observed in parallel-mode electron paramagnetic resonance (EPR) spectroscopy that was generated by the addition of CaII ions and base to a MnIV-oxido complex within the [H2bupa]3– ligand.

A central tenet of chemistry is the importance of the local environments that surround molecules. Rules for how such local environments control molecular properties have been developed and form the basis for coordination chemistry, an area of chemistry devoted to the study of molecules containing metal ions. Within this context, the volume of space surrounding metal ions is divided into two regions, referred to as the primary and secondary coordination spheres. The primary coordination sphere involves covalent interactions between atoms on ligands that are directly bound to the metal center. The secondary coordination sphere, which involves non-covalent interactions, is part of the volume of space around the metal center and often interacts with the ligands of the primary coordination sphere. Together, the coordination spheres define the physical properties and reactivity of a metal ion. The importance of modulating both is seen within the active sites of metalloproteins, in which the interplay between the two coordination spheres allow these proteins to catalyze difficult reactions under ambient conditions, with selectivities and efficiencies that are currently unattainable in synthetic systems.

One approach towards understanding how the two coordination spheres affect function involves specially designed ligands that account for effects in both coordination spheres. The aim of this dissertation is to study synthetic metal complexes that incorporate these types of ligands, and explore their fundamental physical, structural, and chemical properties. The ligands used are based on the tripodal sulfonamido-based ligand N,N’,N”-[2,2’,2”-nitrilotris(ethane-2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST]3–). This ligand contains a tris(2-aminoethyl)amine (tren) backbone that allows for the preparation of four- or five-coordinate metal complexes with local C3 symmetry to control the primary coordination sphere. The trigonal environment leads to high-spin metal complexes, and the presence of three anionic nitrogen donors helps to stabilize relatively high oxidation states. Secondary coordination sphere effects are modulated through the sulfonamido moieties. The [MST]3– ligand can support monometallic metal complexes with terminal hydroxido, aqua, or ammine ligands, as the sulfonamido moieties can accept H-bonds from H-atom containing exogenous ligands. Additionally, the sulfonamido O-atoms can serve as a secondary metal binding site, allowing discrete bimetallic complexes to be prepared with [MST]3–.

In this dissertation, new monometallic and bimetallic complexes with sulfonamido-based tripodal ligands were prepared, with the goal of understanding how the choice of ligands influences the properties of metal complexes. The first study investigated the effect of ligand modification on the physical properties of a series of FeII–OH2 complexes supported by ligands related to [MST]3–. The aryl groups of the five new N,N',N"-[2,2',2"-nitrilotris(ethane-2,1-diyl)]-tris-({R-Ph}-sulfonamido)) ([RST]3–) ligands had para-substituents of varying electron-withdrawing and donating strengths. The physical properties of the subsequent FeII–OH2 complexes were probed by various characterization methods, which revealed that the greatest impact of the ligand modification occurred in the metal complexes’ electrochemical properties.

Monometallic Ni complexes with [MST]3– and a related urea-based ligand, [H3buea]3–, were then studied. The solid-state structures of these compounds showed that these ligands allowed for the preparation of NiII complexes with terminal aqua or hydroxido ligands in distorted trigonal bipyramidal geometries. Additionally, the oxidation chemistry of both NiII compounds was investigated, allowing for the preparation and characterization of uncommon NiIII complexes.

Bimetallic complexes with [MST]3– are prepared by treating a solution of a monometallic [MST]3– complex, secondary metal salt, and secondary multidentate ligand with O2. The secondary ligand serves to “cap” the secondary metal center, resulting in discretely bimetallic units. A new series of bimetallic complexes with FeII(OH)FeIII, CoII(OH)FeIII, and NiII(OH)FeIII cores was prepared, using the bidentate capping ligand tetramethylethylenediamine (TMEDA). Previously, all other capping ligands used in this system had denticities of three and above. The bidentate capping ligand TMEDA allows the previously outer-sphere trifluoromethansulfonate (OTf–) counter anion to become inner-sphere, occupying the sixth coordination site of the second metal center.

The ability to form heterobimetallic complexes and the presence of the weakly coordinating OTf– ligand prompted an investigation of the substitution chemistry of the system. In the FeII(OH)FeIII species, the OTf– ligand could be directly substituted for either isothiocyanate (NCS–) or azide (N3–) ligands. Additionally, a Br– ligand can occupy the sixth coordination site of the FeII center if the preparation of the diiron complex was modified. Furthermore, the TMEDA capping ligand can be directly substituted for two ethylenediamine (en) ligands. These results stress the importance of the choice of the capping ligand in these types of compounds, which has important implications on the substitution chemistry of this bimetallic system.

In nature, metalloproteins can perform difficult transformations with high selectivity and efficiency through precise control of the primary and secondary coordination sphere. Synthetic chemists have developed biomimetic ligand scaffolds to better understand the coordination environments in the active sites of metalloproteins. However, besides the ligands covalently bound to the metal center, secondary coordination sphere that is comprised of non-covalent interactions also has significant influence in complex properties. This dissertation describes how modulation of the secondary coordination sphere by incorporating different H-bond donors or acceptors affects the chemistry of metal complexes. Chapter 2 describes a series of MnIII-oxido complexes within the hybrid tripodal framework, [H3bpuea-R]3‒, which one of the ligand arms contains a para-substituted phenyl ring. Varying the R-groups on the phenyl ring allowed modulation on the strength of one single H-bond donor in the secondary coordination sphere without perturbing the primary coordination sphere. This modulation showed influences on basicity and reactivity of the MnIII-oxido complexes. Chapter 3 describes newly synthesized FeII/III-NH3 and FeIII-amido complexes in C3-symmetric tripodal phosphinic amido ligand framework, [poat]3–. Comparing the FeII/III-NH3 complexes in the [poat]3– ligand framework and analogous complexes in [MST]3– ligand framework showed significant differences in their structural and redox properties, suggesting [poat]3– can serve as a stronger donor ligand and provide stronger H-bonding interactions. Chapter 4 describes the reactivity of a high spin FeIV-oxido complex, [FeIVPOP(O)]–, in C3-symmetric tripodal phosphoryl amido ligand framework. Taking inspiration from TauD having substrate anchored in close proximity of the metal center, benzyl alcohol was used as a substrate that can participate in possible H-bond interaction with the P=O in phosphoryl amido arms of the complex. Reactivity of [FeIVPOP(O)]– with benzyl alcohol was observed. Hammett analysis and determination of kinetic isotope effect (KIE) for the reactions were performed. The KIE values suggest the cleavage of the C–H bond is involved in the rate determining step whereas the cleavage of the O–H bond is not. Furthermore, the reaction rate of the [FeIVPOP(O)]– complex with benzyl alcohol was ~100 times larger than that of the [FeIVpoat(O)]– complex. This result showed two complexes in similar primary coordination sphere can have significantly different reactivities by modification of the secondary coordination sphere around the FeIV-oxido moiety. In chapter 5, extending the study of the C3-symmetric tripodal phosphoryl amido ligand framework, [POP]3–, binding of α-keto acids such as sodium phenylpyruvate (NaPhP) and phenylgloxylic acid (PGA) were studied as exogenous ligand for iron complex. The Na(NMe4)[FeIIHPOP(PhP)] complex was isolated and characterized. Intramolecular tautomerization was observed in the FeII-PhP complex with the [PhP]2– ligand bound as enolate form and one of the phosphoryl amide arms protonated. Preliminary UV-vis and EPR results for reactivities of the α-keto acids bound iron complexes with O2 showed possible oxidation of the iron center

In nature, metal ions are utilized in many proteins and enzymes in order to perform a variety of chemical transformations that are essential to maintaining human life. The range of selectivity and functionality can be attributed to the unique environment surrounding each active site, which allow for control over not only the primary coordination sphere—containing atoms covalently bound to the metal ion, but also the secondary coordination sphere (microenvironment)—made up of non-covalent interactions such as hydrogen bonds (H-bonds). Although nature is very efficient at these chemical processes, achieving the same level of selectivity is difficult in synthetic systems. In order to reproduce the functions found in metalloproteins it is necessary to maintain control over both the primary and secondary coordination spheres of synthetic systems as seen within active sites. To accomplish this, typically a rigid organic framework is constructed that will coordinate to a metal ion and additionally provide a supporting network of non-covalent interactions: intramolecular H-bonds.

The Borovik group has performed extensive research the area of secondary coordination sphere effects around transition metal complexes and has developed a multitude of ligand frameworks that bind metal ions and incorporate intramolecular H-bond donors or acceptors that can stabilize exogenous ligands bound to the transition metal (TM) complexes. While these systems have been extremely effective and have been used to prepare unique high-valent metal-oxo/hydroxo species, they fall short in being able to provide extensive networks of H-bonds and long-range interactions found in microenvironments of metalloproteins. To address these challenges and gain further control over the secondary coordination sphere, this dissertation presents the development of new research program within the Borovik group in collaboration with the Ward lab: the development of artificial metalloproteins using biotin-Streptavidin (Sav) technology. Although Sav does not naturally contain metal ions, TM complexes of interest can be attached to biotin and inserted into the protein. This is an attractive feature, because of Sav’s exceptionally high affinity for biotin , which can be exploited for the use of installing biotinylated metal complexes. Furthermore, the selective binding of biotin provides a reproducible anchor for TM complexes within the active site of protein. In addition to being able to chemically modify a ligand, the protein is amenable to site directed mutagenesis, which allows for alterations of the microenvironment around the TM complexes. This combined chemogenetic approach allows for enhanced control over primary and secondary coordination spheres of TM complexes.

The first portion of this document describes the study of biotinylated copper(II) complexes with varied linker lengths between the Cu(II) complex and biotin. Utilizing different linker lengths was proposed to allow for: 1) to design discrete monomeric species confined within separate subunits or 2) to create a bimetallic systems at the dimer interface. Additionally, different mutants of Sav varying the amino acid residue at a site proximal to the Cu(II) complex were investigated to observe the protein effects on the secondary coordination sphere of the TM complex. Changing the serine at the112 position to either lysine, aspartate, or cysteine had drastic effects on the microenvironment of the Cu(II) complex. This was studied through Uv-Vis and electronic paramagnetic resonance (EPR) spectroscopies, and X-ray diffraction studies (XRD). XRD studies explicitly showed the molecular structures of the Cu(II) complexes bound within Sav and the effects of linker length changes and site directed mutagenesis. This research has shown proof of concept that Cu(II) complexes can be prepared within Sav and different microenvironments can be reproducibly attained with different linker lengths and protein mutants, and my work has established this methodology as a promising new research program within the group.

Another way of harnessing the dimer-of-dimers nature of Sav would be to prepare a TM complex linked to two biotin molecules to potentially bridge across two subunits of the protein. As reproducibility and rigidity of a binding environment is essential to selectivity in chemical transformations, this was envisioned as a method of firmly anchoring a TM complex within the protein to be studied further. To probe this hypothesis a bis-biotinylated Schiff-base was prepared and its binding to Sav studied using HABA titrations and gel electrophoresis. It was shown that instead of bridging two subunits in a homotetramer, the ligand and its complexes bridged separate Sav molecules to form oligomers of proteins.

Prior to developing the biotin-Sav program, I investigated the use of well-established tripodal, tetradentate ligands within the Borovik lab. Previous research within the lab had shown that the Fe(II) complexes of these ligands were capable of activating aryl azides to form Fe(III)-amido compounds via a putative Fe(IV)-imido intermediates. It was proposed that this would be amenable to a catalytic system wherein a C¬–H bond within an aryl azide substrate could be activated by an Fe(IV)-imido and I anticipated subsequent radical rebound would form a new C–N bond. However, the system did not demonstrate the ability to perform C–H amination.

Metalloenzymes are efficient catalysts, operating both stereo- and regioselectively with high reaction rates at ambient temperatures in aqueous conditions. In order to generate synthetic catalysts which operate in similarly efficient pathways, it is useful to study biomimetic

complexes which incorporate the techniques used by biological systems. In this report, several pincer ligand frameworks are used to incorporate the interplay between primary coordination sphere effects and secondary coordination sphere effects observed in metalloenzyme active sites. H4dippy, which combines appendant dipeptides to create a chiral environment as well as distal hydrogen-bonding groups was prepared and used to generate CuIIH2dippy. Further experiments probed the oxidation of CuIIH2dippy with aqueous H2O2. A new phosphonamide bis(aminophenyl)amine ligand, H3tap, was used to prepare a cobalt(II) complex with optical

features consistent with a [Co2N2] diamond core structure. Reaction with oxidants generated species with spectroscopic characteristics consistent with ligand oxidation and retention of a dinuclear complex. Finally, the redox-active sulfonamide bis(aminophenyl)amine, H3ibaps, as well as H3tap, were used to generate putative iron(III) thiolate complexes. These complexes were studied by reaction with the oxo-transfer reagent isopropyl iodoxybenzoate and subsequent reaction with substrates

Metal ion cofactors within active sites are essential components for many proteins and have been directly linked to function. Active sites contain either a single or multiple metal ion(s) participating in a mixture of covalent and non-covalent interactions that function cooperatively to perform efficient and selective chemical transformations. Non-covalent interactions are often found within the volume of space that surrounds the metallocofactors, denoted as the microenvironment, which influence key properties such as the transfer of protons and electrons. Non-covalent interactions are the major forces that influence the microenvironments within protein active sites with hydrogen bonds (H-bonds) being the most dominant. Using these architectural features as inspiration, the works of this dissertation describes the design, preparation, and characterization of Mn/Fe– oxido and hydroxido complexes supported by frameworks that incorporate phosphoryl amide moieties.

Chapter 2 introduces the development of new ligand frameworks containing phosphorus. The design premise behind the usage of phosphoryl amides was that the deprotonated phosphoryl amide nitrogen atom would produce a ligand field that stabilizes high valent complexes, and that the P=O units would serve as an H-bond acceptor, an auxiliary metal binding site, and produce a negative polarized cavity to help stabilize high valent metal–hydroxido/oxido complexes.

Chapters 3 and 4 describe the development of Mn/Fe–OH complexes of the hybrid ligand [H2pout]3- that installs a combination of two H-bond donors and one H-bond acceptor within the secondary coordination sphere. The [H2pout]3- ligand was used to prepare the MII–OH complexes, which had sufficiently low redox potentials to synthetically prepare its corresponding Mn–O(H) (n = III, IV) analogs.

In Chapter 5 of this dissertation a new high spin, FeIV¬–oxido complex supported by a symmetrical phosphinic amide tripod is discussed along with its reactivity with Lewis acids. A series of LA (LA = Mg2+, Ca2+, Sr2+, Ba2+, and H+) were added to the FeIV–oxido complex and generated distinct FeIV species. The vibrational data shows a clear change in the Fe–O vibrations when Mg2+ or Ca2+ ions are added, corroborating that these ions affect the FeIV–oxido unit. Preliminary data with H+ suggests that protons interact with the FeIV–oxido complex, but not at the FeIV–oxido unit, suggesting that an FeIV–OH species is not produced.

Chapter 6 takes a different approach to generating an FeIV–OH species. The beginning of this chapter discussed the preparation and characterization of low valent Fe–aqua/hydroxide complexes within [poat]3- scaffold. The FeII/III–OH complexes have similar properties as previously developed frameworks; however, once oxidized beyond FeIII–OH, the reactivity is different. The one-electron oxidized complex exhibits magnetic properties that are unprecedented to anything we have seen before and has been assigned as an S = 2 system containing a high spin FeIII center antiferromagnetically coupled to a ligand radical.

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.

Metal ions are ubiquitous in biology and aid in facilitating many enzymatic transformations. For instance, high–valent iron–oxido and –hydroxido species are proposed to be key intermediates in oxidative processes catalyzed by non-heme iron proteins. A subclass of these proteins contains bimetallic sites that house either FeFe or FeM cores. To investigate the properties of both mono- and bimetallic cores, the Borovik Lab has developed a symmetric tripodal ligand framework containing phosphinic amido groups ([poat]3–), which can stabilize high-valent metal centers, provide an auxiliary binding-site for a second metal ion, and contains a pendant arm that can provide hydrogen-bond stabilization as well as facilitate proton shuttling. The work presented in this dissertation describes my efforts to access high-valent homo-/heterobimetallic oxido and hydroxido species by a variety of synthetic routes.

Chapter 1 provides an overview of bimetallic proteins, and efforts by chemists to synthetically model the structure and function of these active sites. Previous work performed in the Borovik Lab to approach these synthetic challenges is discussed.

Chapter 2 explores the oxidation chemistry of the mononuclear complexes FeII– and FeIII–hydroxido complexes in the [poat]3– framework, which serve as important synthons in the stepwise assembly of subsequent bimetallic complexes. While previous members in the Borovik Lab have studied these complexes, the electrochemical properties of these compounds are reassessed in my effort to access high-valent Fe–hydroxido species.

Chapters 3 and 4 introduce the synthesis and characterization of discrete heterobimetallic complexes, with an MII–OH–FeIII or MII–O–FeIV core (M = Zn, Cu, Ni). This stepwise assembly approach allows for the formation of dinuclear compounds in an unsymmetric framework. The Fe center is supported by the [poat]3– ligand, while MII is supported by an N-based macrocycle. These species are compared with bimetallic complexes in similar frameworks.

Chapters 5 describes the preparation of a series of di-Fe compounds with an Fe–O–Fe or Fe–OH–Fe core. These complexes are housed within the same unsymmetric scaffold, and span across four oxidation levels, from FeIIFeII to FeIIIFeIV. This study illustrates the multifunctional nature of the [poat]3- framework, and provides useful insight into the thermodynamic parameters of proton and electron transfers in bimetallic systems. These findings have significant implications for di-Fe containing enzymes, such as ribonucleotide reductase and soluble methane monooxygenase.

Using the synthetic strategies developed in the previous chapters, Chapters 6 and 7 describe the preparation and characterization of a library of FeMn and MnFe complexes to model their biological counterparts. Their structural, electrochemical, magnetic, and reactivity properties are discussed. An FeIII–O–MnIV species was trapped and studied spectroscopically, and its relevance to similar high valent FeMn active sites is biology is discussed.

Chapter 8 discusses the observation of a rare high-spin CoIII center in a bimetallic system via different spectroscopic techniques. This is an unusual finding, as most six-coordinated CoIII complexes adopt a low-spin configuration due to significant ligand field stabilization. A series of CoFe and CoGa complexes were prepared to probe the factors for this phenomenon, including the P=O groups in [poat]3- being weak field ligands, and modulation of spin exchange interactions.

Abstract of the DissertationPreparation and Properties of Mono- and Bimetallic Paramagnetic Co Complexes Supported by Tripodal Ligand Frameworks by Meghen E. Goulet Doctor of Philosophy in Chemistry University of California, Irvine, 2022 Distinguished Professor Andrew S. Borovik, Chair Many important and synthetically challenging chemical reactions are carried out by metalloenzymes, including water oxidation, nitrogen fixation, O2 reduction, and oxidation of C–H bonds in substrates such as methane, fatty acids, and pharmaceutical products. Metalloenzymes are able to catalyze these reactions in part due to their ability to access reactive intermediates which is facilitated by the protein host. To replicate these effects synthetically, the Borovik lab designs organic ligands that incorporate both primary and secondary coordination sphere interactions to control the local environment within metal complexes. This dissertation presents research that employs these ligand frameworks in both mono- and bimetallic small molecule Co complexes. Chapter 1 provides a brief introduction to key features of metalloenzyme active sites that support their reactivity. A concise overview of relevant synthetic ligand designs is given, in addition to summaries of the following chapters. Chapter 2 describes the preparation of mononuclear CoII– and CoIII–OH complexes within an unsymmetric, hybrid tripodal ligand framework: [H2pout]3–. The characterization of these complexes is discussed, including the molecular structure of K[CoIIIH2pout(OH)]. xx K[CoIIIH2pout(OH)] is paramagnetic, an unusual trait for a CoIII center. The reactivity of K[CoIIIH2pout(OH)] towards substrates with an O–H bonds is also examined. This work is the first reactivity study of a CoIII–OH complex. Chapter 3 describes the preparation of a trigonal monopyramidal, four-coordinate Co complex supported by the C3 symmetric [poat]3– ligand framework. This complex, K[CoIIpoat] is used in Chapter 3 – 5 to prepare unsymmetric bimetallic species. Chapter 3 focuses specifically on the formation of a [poatCoIII–μ-OH–ZnIIMe3tacn]+ complex via a proposed CoII–oxidant adduct that reacts in the presence of [ZnIIMe3tacn(OTf)2], where Me3tacn is a heterocyclic N-based ligand. In Chapter 4, the preparation of a [poatCoII–μ-OH–FeIIIMe3tacn]+ complex from K[CoIIpoat] and O2 in the presence of [FeIIMe3tacn(OTf)2] is discussed. The [poatCoII–μ-OH–FeIIIMe3tacn]+ complex is subsequently oxidized to [poatCoIII–μ-OH–FeIIIMe3tacn]2+ and the changes in the magnetic coupling between the Co and Fe centers are examined. Mössbauer and EPR spectroscopies support antiferromagnetic coupling in [poatCoII–μ-OH–FeIIIMe3tacn]+, but ferromagnetic coupling in [poatCoIII–μ-OH–FeIIIMe3tacn]2+. Finally, Chapter 5 describes the development of a new series of bimetallic species, [Mx IIpoat⋅⋅⋅My IIMe3tacn]+, (Mx = Mn, Co, Zn; My = Mn, Fe, Co, Cu, Zn). The metal ion coordinated in the [poat]3– ligand backbone is in a trigonal monopyramidal geometry, which is shielded by the binding of a [My IIMe3tacn]2+ solely through the P=O groups. The two metal ions interact through three, triple-atom N–P=O bridging units and are highly symmetric, crystallizing in the R3 space group. The metal ions were found to couple ferromagnetically to one another through the N–P=O bridges and the magnetism of these complexes was studied to determine if the complexes exhibit single molecule magnetic behavior. While the [CoIIpoat⋅⋅⋅My IIMe3tacn]+ complexes were most thoroughly investigated, the [Mx IIpoat⋅⋅⋅My IIMe3tacn]+ have also been prepared where Mx = Mn, Zn and My = Mn, Zn, suggesting that these complexes could be expanded to a wide array of metal ion.