Investigation of the Electronic Structure and Reactivity of Non-Heme Iron Nitrosyl and Nitroxyl Complexes.

High-spin non-heme ferrous nitroxyl (NO-) complexes ({FeNO}8 in the Enemark-Feltham notation) have been proposed as important intermediates in bacterial nitric oxide reductases. Despite their significance, model compounds for these species have remained elusive and prior to the studies described here, little was known about their spectroscopic properties and reactivity. The work presented in this dissertation provides, for the first time, detailed insight into the properties of high-spin {FeNO}8 complexes. The first high-spin non-heme {FeNO}8 complex has been synthesized via chemical or electrochemical reduction of a ferrous nitrosyl ({FeNO}7) precursor. The use of a sterically encumbering ligand prevents the disproportionation typically observed for {FeNO}8 complexes. A rare high-spin ferric nitrosyl ({FeNO}6) species has also been generated using the same ligand. This system constitutes the first complete high-spin {FeNO}6-8 series. Detailed spectroscopic investigations coupled to DFT calculations show that the {FeNO}6, {FeNO}7, and {FeNO}8 complexes have Fe(IV)-NO-, Fe(III)-NO-, and Fe(II)-NO- electronic structures, respectively. Importantly, the covalency of the Fe-NO bond decreases along this series. This has implications for the reactivity of these species. For example, only the {FeNO}8 complex, in which the Fe-NO bond is weakest, is basic. Protonation of the {FeNO}8 yields a highly unstable species which, based on spectroscopic investigations, is suggested to be the first high-spin Fe(II)-HNO complex. The decomposition of other {FeNO}8 compounds has also been investigated. Our group previously showed that rapid and efficient N2O production can be achieved by reduction of [{FeNO}7]2 dimers with adjacent NO moieties. Here, it is demonstrated that N2O production is slow and substoichiometric when the NO units are not in close proximity to each other. Additionally, it is shown that for monomeric compounds, one prominent decomposition pathway involves disproportionation, leading to formation of a dinitrosyl iron complex (DNIC). Finally, in a separate study, the electronic structure of DNICs at the {Fe(NO)2}9 and {Fe(NO)2}10 redox levels has been investigated using Mossbauer and vibrational spectroscopy. By coupling the findings from these techniques to DFT calculations, the bonding in these species is shown to be extremely covalent which explains their high stability.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133281/1/alspeelm_1.pd

Expanding and Testing a Computational Method for Predicting the Ground State Reduction Potentials of Organic Molecules on the Basis of Empirical Correlation to Experiment

A method for predicting the ground state reduction potentials of organic molecules on the basis of the correlation of computed energy differences between the starting S-0 and one-electron-reduced D-0 species with experimental reduction potentials in acetonitrile has been expanded to cover 3.5 V of potential range and 74 compounds across 6 broad families of molecules. Utilizing the conductor-like polarizable continuum model of implicit solvent allows a global correlation that is computationally efficient and has improved accuracy, with r(2) \u3e 0.98 in all cases and root mean square deviation errors of(mean absolute deviationsmV) for either B3LYP/6-311+G(d,p) or B3LYP//6-31G(d) with an appropriate choice of radii (UAKS or UA0). The correlations are proven to be robust across a wide range of structures and potentials, including four larger (27-28 heavy atoms) and more conformationally flexible photochromic molecules not used in calibrating the correlation. The method is also proven to be robust to a number of minor student mistakes or methodological inconsistencies

Synthesis and Structural Investigation of an \u27Oxazinoquinolinespirohexadienone\u27 That Only Exists as Its Long-Wavelength Ring-Opened Quinonimine Isomer

The spirocyclic oxazinoquinolinespirohexadienone (OSHD) photochromes are computationally predicted to be an attractive target as electron deficient analogues of the perimidinespirohexadienone (PSHD) photochromes, for eventual application as photochromic photooxidants. We have found the literature method for their preparation unsuitable and present an alternative synthesis. Unfortunately the product of this synthesis is the long wavelength (LW) ring-opened quinonimine isomer of the OSHD. We have found this isomer does not close to the spirocyclic short wavelength isomer (SW) upon prolonged standing in the dark, unlike other PSHD photochromes. The structure of this long wavelength isomer was found by NMR and X-ray crystallography to be exclusively the quinolinone (keto) tautomer, though experimental cyclic voltammetry supported by our computational methodology indicates that the quinolinol (enol) tautomer (not detected by other means) may be accessible through a fast equilibrium lying far toward the keto tautomer. Computations also support the relative stability order of keto LW over enol LW over SW

Efficient Computational Methods for Accurately Predicting Reduction Potentials of Organic Molecules

A simple computational approach for predicting ground-state reduction potentials based upon gas phase geometry optimizations at a moderate level of density functional theory followed by single-point energy calculations at higher levels of theory in the gas phase or with polarizable continuum solvent models is described. Energies of the gas phase optimized geometries of the S0 and one-electron-reduced D0 states of 35 planar aromatic organic molecules spanning three distinct families of organic photooxidants are computed in the gas phase as well as well in implicit solvent with IPCM and CPCM solvent models. Correlation of the D0 − S0 energy difference (essentially an electron affinity) with experimental reduction potentials from the literature (in acetonitrile vs SCE) within a single family, or across families when solvent models are used, yield correlations with r2 values in excess of 0.97 and residuals of about 100 mV or less, without resorting to computationally expensive vibrational calculations or thermodynamic cycles

Structural and Spectroscopic Characterization of a High‐Spin {FeNO}6 Complex with an Iron(IV)−NO− Electronic Structure

Although the interaction of low‐spin ferric complexes with nitric oxide has been well studied, examples of stable high‐spin ferric nitrosyls (such as those that could be expected to form at typical non‐heme iron sites in biology) are extremely rare. Using the TMG3tren co‐ligand, we have prepared a high‐spin ferric NO adduct ({FeNO}6 complex) via electrochemical or chemical oxidation of the corresponding high‐spin ferrous NO {FeNO}7 complex. The {FeNO}6 compound is characterized by UV/Visible and IR spectroelectrochemistry, Mössbauer and NMR spectroscopy, X‐ray crystallography, and DFT calculations. The data show that its electronic structure is best described as a high‐spin iron(IV) center bound to a triplet NO− ligand with a very covalent iron−NO bond. This finding demonstrates that this high‐spin iron nitrosyl compound undergoes iron‐centered redox chemistry, leading to fundamentally different properties than corresponding low‐spin compounds, which undergo NO‐centered redox transformations.Die Ein‐Elektronen‐Oxidation des High‐Spin‐Eisennitrosylkomplexes [Fe(TMG3tren)(NO)]2+ egibt ein seltenes High‐Spin(S=1)‐Eisen‐NO‐Addukt ({FeNO}6), das laut spektroskopischen Untersuchungen und DFT‐Rechnungen eine FeIV‐NO−‐Elektronenstruktur aufweist. Dieser Befund zeigt, dass High‐Spin‐Nicht‐Häm‐Eisennitrosylkomplexe ein fundamental anderes Redoxverhalten als entsprechende Low‐Spin‐Häm‐Systeme haben.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137344/1/ange201601742.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137344/2/ange201601742-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137344/3/ange201601742_am.pd

A Structural Model for the Iron–Nitrosyl Adduct of Gentisate Dioxygenase

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146641/1/ejic201800992_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146641/2/ejic201800992-sup-0001-SupMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146641/3/ejic201800992.pd

The Fe2(NO)2 Diamond Core: A Unique Structural Motif In Non‐Heme Iron–NO Chemistry

Non‐heme high‐spin (hs) {FeNO}8 complexes have been proposed as important intermediates towards N2O formation in flavodiiron NO reductases (FNORs). Many hs‐{FeNO}8 complexes disproportionate by forming dinitrosyl iron complexes (DNICs), but the mechanism of this reaction is not understood. While investigating this process, we isolated a new type of non‐heme iron nitrosyl complex that is stabilized by an unexpected spin‐state change. Upon reduction of the hs‐{FeNO}7 complex, [Fe(TPA)(NO)(OTf)](OTf) (1), the N‐O stretching band vanishes, but no sign of DNIC or N2O formation is observed. Instead, the dimer, [Fe2(TPA)2(NO)2](OTf)2 (2) could be isolated and structurally characterized. We propose that 2 is formed from dimerization of the hs‐{FeNO}8 intermediate, followed by a spin state change of the iron centers to low‐spin (ls), and speculate that 2 models intermediates in hs‐{FeNO}8 complexes that precede the disproportionation reaction.Eine seltene Raute: Der hs‐{FeNO}7‐Komplex 1 wurde durch spektroskopische Methoden und Röntgenkristallographie charakterisiert. Unter reduzierenden Bedingungen wird das Dimer 2 mit rautenförmigem Kern durch Dimerisierung eines hs‐{FeNO}8‐Zwischenprodukts und anschließende Spinzustandsänderung der Eisenzentren zu Low‐Spin (ls) gebildet.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152586/1/ange201911968_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152586/2/ange201911968-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152586/3/ange201911968.pd

Modeling Fluorescence Observables, Particularly for FRET Experiments, using Markov Chain Analysis of Molecular Dynamics and Quantum Mechanics Simulations

We present a new method for simulating fluorescence observables, particularly those related to bulk and single-molecule fluorescence-detected resonance energy transfer (FRET) experiments. In this method, a molecular dynamics (MD) simulation is used to sample configuration space and quantum mechanics (QM) calculations are used to estimate the electronic coupling between the donor and acceptor probes for snapshots along the MD trajectory. A Markov chain method is used to sample the resulting electronic coupling trajectory allowing accurate simulation of any desired fluorescence observables, such as FRET efficiency histograms or time-resolved donor fluorescence decays. The Markov chain results will be compared with the results of simple histogram and averaging schemes showing that the Markov chain is the only one that yields realistic results in well known examples such as the rapid diffusion limit. This combination of computational methods also avoids some pitfalls of traditional FRET analysis such as the kappa-squared and the ideal dipole approximations. Because the simulation results can be compared directly with experimental observables, this method may allow more detail to be derived from experiment than is traditionally possible. 3037-PosB80

The Fe2(NO)2 Diamond Core: A Unique Structural Motif In Non‐Heme Iron–NO Chemistry

Non‐heme high‐spin (hs) {FeNO}8 complexes have been proposed as important intermediates towards N2O formation in flavodiiron NO reductases (FNORs). Many hs‐{FeNO}8 complexes disproportionate by forming dinitrosyl iron complexes (DNICs), but the mechanism of this reaction is not understood. While investigating this process, we isolated a new type of non‐heme iron nitrosyl complex that is stabilized by an unexpected spin‐state change. Upon reduction of the hs‐{FeNO}7 complex, [Fe(TPA)(NO)(OTf)](OTf) (1), the N‐O stretching band vanishes, but no sign of DNIC or N2O formation is observed. Instead, the dimer, [Fe2(TPA)2(NO)2](OTf)2 (2) could be isolated and structurally characterized. We propose that 2 is formed from dimerization of the hs‐{FeNO}8 intermediate, followed by a spin state change of the iron centers to low‐spin (ls), and speculate that 2 models intermediates in hs‐{FeNO}8 complexes that precede the disproportionation reaction.A rare diamond: The hs‐{FeNO}7 complex 1, was characterized by spectroscopic methods and X‐ray crystallography. Upon reduction, the diamond‐core dimer 2 is formed by dimerization of an hs‐{FeNO}8 intermediate, followed by a spin state change of the iron centers to low‐spin (ls).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152873/1/anie201911968.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152873/2/anie201911968_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152873/3/anie201911968-sup-0001-misc_information.pd