MONONUCLEAR NONHEME IRON(II) MODEL COMPLEXES WITH MIXED N/S DONOR SETS: PRIMARY AND SECONDARY COORDINATION SPHERE EFFECTS
| dc.contributor.advisor | Goldberg, David P. | en_US |
| dc.contributor.committeeMember | Karlin, Kenneth D. | en_US |
| dc.contributor.committeeMember | Greenberg, Marc M. | en_US |
| dc.creator | Widger, Leland Robert | en_US |
| dc.date.accessioned | 2014-12-23T04:35:40Z | |
| dc.date.available | 2014-12-23T04:35:40Z | |
| dc.date.created | 2014-05 | en_US |
| dc.date.issued | 2014-01-27 | en_US |
| dc.date.submitted | May 2014 | en_US |
| dc.description.abstract | Oxygen defines the aerobic environment in which much of life on earth exists. Nature has necessarily evolved a number of metalloenzyme-catalyzed reactions that utilize, as well as protect against, molecular oxygen (O2) and its derivatives. Dioxygen is a particularly interesting molecule; it is found in nature mostly as a triplet diradical, rendering an otherwise powerful oxidizing agent relatively inert toward organic matter since reactions are spin-forbidden under standard conditions. However when activated by an appropriate catalyst (usually a transition metal), triplet oxygen can become extremely reactive in the form of singlet oxygen or one of a series of species that are collectively called “reactive oxygen species” (ROS). These ROS (superoxide, hydrogen peroxide, hydroxyl radical, organic peroxides and peroxynitrite) are responsible for performing some of the most important and recognizable reactions in biochemistry. In the Goldberg research group, we are particularly interested in unraveling the mysteries of what some refer to as the “oxygen economy,” the many reactions which ultimately make up a global cycle between H2O and O2. One general class of enzymes that contribute to this cycle are the nonheme iron oxygenases, enzymes that active O2 to oxidize a substrate utilizing a non-porphyrinoid iron center. The nonheme iron oxygenases encompass a massive variety of individual centers, each with its own unique ligand set and subsequent function. We are particularly interested in understanding the role of sulfur, which is present in some of these enzymes, and my interests have focused on building synthetic model systems inspired by two specific nonheme iron metalloenzymes that contain iron- sulfur centers: cysteine dioxygenase (CDO) and superoxide reductase (SOR). By making structural models of these systems we hope to build our understanding of the specific ii ligand environment around the iron centers, and how they impart the observed reactivity and selectivity at the metal center. One interesting property of metalloenzymes is their ability to incorporate redox cofactors or non-innocent ligands that have been implicated as critical aspects of various enzymatic reactivity. Chapter 2 discusses a study where an additional reducing equivalent was incorporated into a CDO model complex, known to undergo biomimetic S- oxygenation. The known iron(II) complex [FeII(LN3S)(OTf)] was used as starting material to prepare the new biomimetic (N4S(thiolate)) iron(II) complexes [FeII(LN3S)(py)](OTf) and [FeII(LN3S)(DMAP)](OTf), where LN3S is a tetradentate bis(imino)pyridine (BIP) derivative with a covalently tethered phenylthiolate donor. These complexes were characterized by X-ray crystallography, UV-vis, 1H NMR, and Mössbauer spectroscopy, as well as electrochemistry. A nickel(II) analogue, [NiII(LN3S)](BF4), was also synthesized and characterized by structural and spectroscopic methods. Cyclic voltammetric studies showed all of these complexes undergo a single reduction process with E1/2 between -0.9 to -1.2 V versus Fc+/Fc. Treatment of [FeII(LN3S)(DMAP)](OTf) with 0.5% Na/Hg amalgam gave the mono-reduced complex [Fe(LN3S)(DMAP)]0, which was characterized by X-ray crystallography, UV-vis, EPR (g = [2.155, 2.057, 2.038]) and Mössbauer (δ = 0.33 mm s-1; ΔEQ = 2.04 mm s-1) spectroscopies. Computational methods (DFT) were also employed to model these complexes. The combined experimental and computational studies show that the iron(II) starting matierials are all 5-coordinate, high-spin (S = 2) FeII complexes, whereas [Fe(LN3S)(DMAP)]0 is best described as a 5-coordinate, intermediate-spin (S = 1) FeII complex antiferromagnetically coupled to a ligand radical. This unique electronic iii configuration leads to an overall doublet spin (Stotal = 1⁄2) ground state. The new ferrous starting complexes are shown to react with O2 to give S-oxygenated products, as previously reported. In contrast, the mono-reduced analogue appears to react with O2 to give a mixture of S- and Fe-oxygenates. The nickel(II) complex does not react with O2, and even when the mono-reduced nickel complex is produced, it appears to undergo only outer-sphere oxidation with O2. Inspired by recent success in iron(II) mediated S(thiolate)-oxidation, we sought to determine if this methodology could be expanded to sulfide donors. Sulfide oxidation is an important strategy in organic chemistry, and more recently has attracted attention for its use in desulfurization of fossil fuels. In chapter 3, the unsymmetrical iron(II) bis(imino)pyridine complexes [FeII(LN3SMe)(H2O)3](OTf)2, and [FeII(LN3SMe)Cl2] were synthesized and their reactivity with O2 was examined. These complexes were characterized by single crystal X-ray crystallography, LDI-MS, 1H-NMR and elemental analysis. The LN3SMe ligand was designed to incorporate a single sulfide donor and relies on the bis(imino)pyridine scaffold. This scaffold was selected for its ease of synthesis and its well-precedented ability to stabilize Fe(II) ions. The reported complexes ware prepared via a metal-assisted template reaction from the unsymmetrical pyridyl ketone precursor 2-(O=CMe)-6-(2,6-(iPr2-C6H3N=CMe)-C5H3N. Reaction of [FeII(LN3SMe)(H2O)3](OTf)2 with O2 was shown to afford the S-oxygenated sulfoxide complex [Fe(LN3S(O)Me)(OTf)]2+, whereas [FeII(LN3SMe)Cl2], under the same reaction conditions, afforded the corresponding sulfone complex [Fe(LN3S(O2)Me)Cl]2+. High-valent iron(IV)-oxo species are implicated as key intermediates in a number of enzymatic and synthetic systems. In chapter 4, the synthesis of the new ligand iv N3PyamideSR and its FeII complex [FeII(N3PyamideSR)](BF4)2 are described. Reaction of [FeII(N3PyamideSR)](BF4)2 with PhIO at –40 °C gives metastable [FeIV(O)(N3PyamideSR)]2+, containing a sulfide ligand and a single amide H-bond donor in proximity to the terminal oxo group. Direct evidence for H-bonding is seen in a structural analog, [FeII(Cl)(N3PyamideSR)](BF4)2. The novel [FeIV(O)(N3PyamideSR)]2+ complex exhibits rapid O-atom transfer (OAT) toward external sulfide substrates, but no intramolecular OAT. However direct S-oxygenation does occur in the reaction of [FeII(N3PyamideSR)](BF4)2 with mCPBA, yielding sulfoxide-ligated [FeII (N3PyamideS(O)R)](BF4)2. Catalytic OAT with [FeII(N3PyamideSR)](BF4)2 was also observed. Iron(III)-(hydro)peroxo and (alkyl)-peroxo species are believed to be important species in a variety of reactions resulting from enzymatic O2 activation. In chapter 5, two sulfide-incorporated N4Py derivatives, [FeII(N3PySR)(CH3CN)](BF4)2 and [FeII(N3PyamideSR)](BF4)2, were synthesized and characterized. These starting complexes, afforded rare examples of metastable Fe(III)-OOH and Fe(III)-OOtBu complexes containing equatorial sulfide ligands and a single H-bond donor in the second coordination sphere. These peroxo complexes were characterized by a range of spectroscopic methods and density functional theory (DFT). The influence of a sulfide ligand and of one H-bond donor on the stability and spectroscopic properties of these complexes was investigated. | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.uri | http://jhir.library.jhu.edu/handle/1774.2/36924 | |
| dc.language | en | |
| dc.publisher | Johns Hopkins University | |
| dc.subject | Non-heme | en_US |
| dc.subject | Iron | en_US |
| dc.subject | Oxygen | en_US |
| dc.title | MONONUCLEAR NONHEME IRON(II) MODEL COMPLEXES WITH MIXED N/S DONOR SETS: PRIMARY AND SECONDARY COORDINATION SPHERE EFFECTS | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Chemistry | en_US |
| thesis.degree.discipline | Chemistry | en_US |
| thesis.degree.grantor | Johns Hopkins University | en_US |
| thesis.degree.grantor | Krieger School of Arts and Sciences | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Ph.D. | en_US |