Hydrogen Sulfide (H2S) is an important biologically produced gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Unlike CO and NO, the bioinorganic chemistry of H2S reactivity with biologically relevant metal centers remains underinvestigated. To address this gap, several model bio(in)organic complexes were used to understand the ligation and reaction chemistry of H2S, including phthalocyanine, protoporphyrin IX, tetraphenyl porphyrin, and a pyridine diimine zinc complex. In addition to being a reactive gasotransmitter, the hydrosulfide anion (HS–) has been found to be an important biological anion. Studies with readily available cobalt and zinc phthalocyanines in organic solution illustrated the importance of protonation state in the ligation and redox chemistry of H2S and highlighted the need for an organic-soluble source of HS–. To address this need, we developed a simple method to prepare tetrabutylammonium hydrosulfide (NBu4SH). Using NBu4SH, we expanded the knowledge of H2S reaction chemistry to encompass a significantly larger set of biologically relevant metals beyond iron using the protoporphyrin IX scaffold, revealing three principle reaction pathways: binding, no response, or reduction and binding. Iron in biology is of particular importance given its role in oxygen transport in hemoglobin. The swamp-dwelling bivalve L. Pectinata hemoglobin 1 (Hb1) transports H2S, via ligation to heme, to symbiotic bacteria. The stabilization of H2S in Hb1 is believed to be from one of the following: a protected pocket, hydrogen bonding with a proximal glutamate residue, or a complex combination of these or other factors. By using Collman's "Picket-Fence" porphyrin to isolate the protected pocket model, we determined that a protected pocket alone as insufficient to account for H2S stabilization on Hb1. This realization led to an examination of hydrogen bonding in the secondary coordination sphere of a zinc complex. Finally, we explored the role of HS– as a biologically relevant anion using a bis(ethynylaniline) supramolecular receptor. We determined that rather than covalently modifying the receptor molecule, HS– was bound in the pocket, similar to bacterial anion transport channel. This dissertation includes previously published co-authored material.

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A produção de porfirinas por Corynebacterium diphtheriae é um objeto de estudo antigo, porém pouco explorado em Química e Ciências Médicas. O presente trabalho teve como objetivos comparar a influência de diferentes meios de cultura na produção de porfirinas por Corynebacterium diphtheriae, determinar a influencia da concentração do ferro na produção de porfirina, comparar quantitativamente a produção de porfirinas por diferentes amostras de bacilo diftérico e caracterizar químicamente os tipos de porfirinas produzidas. As técnicas utilizadas para isso foram a espectroscopia de absorção UV-visível e de fluorescência. O meio de cultura descrito por Mueller (1939), para a produção de toxina, se mostrou mais eficiente que o meio B de king, utilizado no diagnóstico laboratorial da difteria. A concentração de ferro no cultivo de Corynebacterium diphtheriae influencia a produção de porfirina. Altas concentrações de ferro inibem a produção de porfirina. A concentração de ferro onde a produção de porfirinas é máxima é de 0,20g/mL. Dentre as 11 amostras de bacilo diftérico estudadas, a amostra HC03, fermentadora de sacarose e toxinogênica, isolada de um caso de endocardite, foi a maior produtora de porfirina. A amostra ATCC de Corynebacterium ulcerans, não fermentadora de sacarose e toxinogênica, foi a amostra que produziu menos porfirina. Todas as 11 amostras apresentaram o mesmo perfil de espectro de fluorescência, sugerindo que a porfirina produzida seja a mesma nas amostras pesquisadas. As análises feitas para a caracterização do tipo de porfirina produzida levam a crer que esta seja uma coproporfirina. Os espectros de absorção e fluorescência não permitem porém determinar o(s) isômero(s) presente(s). / Porphyrin production by Corynebacterium diphtheriae is an old research interest but less attention has been given to the subject in the areas of chemistry and medical sciences. The object of this study is to compare the influence of different culture media in the production of porphyrins by Corynebacterium diphtheriae, to determine the iron concentration influence, to compare quantitatively the production of porphyrins by different samples of diphtheria bacilli and to characterize the porphyrins identities. UV-visible absorption and fluorescence spectroscopies were chosen as analytical tools. The culture medium described by Mueller (1939), for the production of toxin, was more efficient than the medium B of King, used in the laboratory diagnosis of diphtheria. The iron concentration in the cultivation of Corynebacterium diphtheriae influence the production of porphyrin. High concentrations inhibit their production. The iron concentration for maximum production of porphyrins is 0.20  g / mL. Among the 11 studied diphtheria bacillus, the sample HC03, fermented sucrose and toxinogenic, isolated from a case of endocarditis, was the largest producer of porphyrin. The sample of Corynebacterium ulcerans ATCC, unfermented sucrose and toxinogenic was the sample that produced less. All 11 samples showed the same profile of the fluorescence spectrum, suggesting that the porphyrin produced is the same in the samples studied. The tests made to characterize the type of porphyrin produced suggests that this is a coproporphyrin. However, the absorption and fluorescence spectra can not determine which isomer(s) is(are) present

High-valent transition metal-oxo intermediates are of fundamental importance because of their central role as active oxidizing species in enzymatic and synthetic catalytic oxidations. Many transition metal catalysts have been extensively studied as models of the ubiquitous cytochrome P450 enzymes to probe the sophisticated oxygen atom transfer mechanism as well as to invent enzyme-like oxidation catalysts. In this work, photolysis of highly photo-labile corrole-manganese(IV) bromates or nitrites by visible light was studied in two corrole systems with different electronic environments. The corrole systems under studied include 5,10,15- tris(pentafluorophenyl)corrole (TPFC) and 5,10,15-triphenylcorrole (TPC). As observed in both systems, homolytic cleavage of O-Br or O-N bonds in the ligands resulted in one-electron photo-oxidation to generate corrrole-manganese(V)-oxo species, as determined by their distinct UV-vis spectra and kinetic behaviors. The kinetic of oxygen atom transfer (OAT) reactions with various substrates by these photogenerated [MnV(Cor)(O)] were studied in CH3CN and CH2Cl2 solutions. [MnV(Cor)(O)] exhibits remarkable solvent and ligand effects on its reactivity and spectral behaviors. In the more electron-deficient TPFC system and in the polar solvent CH3CN, MnV-oxo corrole returned MnIII corrole in the end of oxidation reaction. However, in the less polar solvent CH2Cl2 or in the less electron-deficient TPC systems, MnIV product was formed instead of MnIII. With the same substrates and in the same solvent, the order of reactivity of MnV-oxo corrole was inverted as TPC > TPFC. The spectra and kinetic results are rationalized by a multiple oxidation model, where the electron-demand MnVoxo species may serve as direct two-electron oxidation for oxygen atom transfer reactions; and less electron-demand systems undergo a disproportionation reaction to form a putative manganese(VI)-oxo corrole as the true oxidant. The choice of pathways is strongly dependent on the nature of the solvent and corrole ligand. Furthermore, porphyrin-manganese(V)-oxo were produced in organic solvents by visible light irradiation of the corresponding porphyrin-manganese(III) nitrite complexes. The porphyrin systems studied were 5,10,15,20-tetrakispentafluoro phenylporphyrin (TPFPP), 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin (TDFPP) and 5,10,15,20-tetrakis(2,6-dichlorophenyl)-porphyrin (TDCPP). Heterolytic cleavage of O-N bond of nitrite ligand results in two-electrons photo-oxidation. Under visible light irradiation, MnV-oxo porphyrins quickly returned to MnIII product. However, in absence of light, MnIV-oxo species were formed, as determined by their distinct UV-vis spectra, which permitted direct kinetic studies. The apparent rate constants for reaction of [MnIV(Por)(O)] species show inverted reactivity order with (TPFPP) < (TDFPP) < (TDCPP) in reactions with ethylbenzene. A model for oxidation under catalytic condition was presented.

Tetrapyrrole sind nicht nur in natürlichen Systemen von herausragender Bedeutung, sondern haben sich im letzten Jahrhundert zu einem zentralen Forschungsgegenstand verschiedener Naturwissenschaften entwickelt. Chirale Vertreter sind, trotz ihrer Bedeutung in der Natur, hierbei nur am Rande untersucht worden. Im Rahmen der vorliegenden Arbeit wurde, ausgehend von p-Xylylen-verbrückten Porphyrinen, sogenannten Henkelporphyrinen, eine Vielzahl an chiralen Strukturen synthetisiert und stereochemisch untersucht. Die monomeren Vertreter waren abhängig vom Substitutionsmuster der Henkeleinheit achiral oder planar-chiral. Über eine kurze und effiziente Syntheseroute wurden die Grundkörper im Multigramm-Maßstab aufgebaut und anschließend sowohl strukturell modifiziert als auch funktionalisiert. Die chiralen Vertreter wurden mittels HPLC an chiraler Phase in die Enantiomere getrennt und mittels online-ECD-Spektroskopie wurden die ECD-Spektren im stopped-flow-Modus gemessen. Der Vergleich mit quantenchemisch berechneten ECD-Kurven erlaubte die sichere Zuordnung der Absolutkonfigurationen. Des Weiteren wurden die Monomere röntgenkristallographisch, UV-Vis-spektroskopisch und elektrochemisch eingehend untersucht. Ausgehend von den monomeren Vertretern wurden mittels direkter oxidativer Kupplung oder über Übergangsmetall-katalysierte Verfahren di- und trimere Systeme aufgebaut. Diese lagen als axial-, helikal- oder planar-chirale Strukturen vor. HPLC-ECD-Kopplung in Verbindung mit quantenchemischen Rechnungen erlaubte auch hier die Aufklärung der absoluten Stereostrukturen. Neben klassischen Porphyrin-Vertretern wurden im Rahmen dieser Arbeit erstmals Henkelchlorine durch OsO4-vermittelte Dihydroxylierung der Henkelporphyrine synthetisiert und vollständig charakterisiert. Außerdem gelang in Kooperation mit Prof. Brückner (UConn) die Aufklärung der Absolutkonfigurationen helikal-chiraler Indachlorine. Die Arbeit liefert insgesamt eine breite Plattform an chiralen Porphyrinoiden, die für weitere Untersuchungen zu Reaktivität und Struktur von größtem Interesse sind, sowie erste detaillierte Einblicke in die faszinierenden Eigenschaften dieser Substanzklasse. / Tetrapyrroles are of outstanding importance not only in naturally occurring systems, but also they have become a central research topic during the last century. Yet, chiral representatives were, despite their importance in nature, only investigated marginally. This work deals with the syntheses and stereochemical investigations of a plethora of chiral Systems based on p-xylylene-bridged porphyrins, so called basket-handle porphyrins. The monomeric representatives were achiral or chiral only by difference of the substitution pattern of the handle unit. Via a short and efficient synthesis, the core motif was accessible in multi-gram quantities. Subsequent modifications as well as functionalizations were achieved. The chiral derivatives were resolved into their enantiomers by HPLC on a chiral phase and their ECD spectra were recorded online in the stopped-flow mode. By comparison with quantum-chemically obtained ECD curves the absolute configurations were established. Additionally, the monomers were characterized by X-ray crystallography, UV-Vis spectroscopy, and electrochemical methods. Starting from the monomers, a variety of di- and trimeric arrays was synthesized by direct oxidative coupling or by transition-metal catalyzed reactions. These systems were either helically, axially, or planar-chiral. HPLC-ECD coupling in combination with quantum-chemical calculations permitted the assignment of the absolute stereostructures. Besides the classical porphyrins, basket-handle chlorins were synthesized by OsO4-mediated dihydroxylation of the basket-handle porphyrins and their absolute configurations were established. Furthermore, in cooperation with Prof. Brückner (UConn) the absolute stereostructures of novel helically chiral Indachlorins was assigned. In summary, this work provides a broad variety of chiral porphyrinoids, which are ideal candidates for further investigations regarding their chemical reactivity and their structural features, and included first detailed insight into the fascinating properties of this class of compounds.

Medium-sized organic ring synthesis poses a seemingly insurmountable challenge, and because of this it is a field under immense investigation. Heterocyclic containing medium-sized rings are common structural motifs in nature, which has caused researchers to investigate their potential biological activity and properties as materials. This research focused on the grand challenge of medium-sized heterocyclic ring synthesis, providing the synthesis community with new tools to generate these highly evasive products, while elucidating energetic and geometric properties of one of Nature's least understood organic ring systems. Cobalt(II)-Amidoporphyrins, [Co(D2-Por)], are an emerging class of metalloradical catalysts (MRC) which can facilitate a wide range of atom and group transfer reactions. A strategy was employed using [Co(D2-Por)] to carry out an intramolecular C-H amination reaction using sulfamoyl azides as the radical nitrene source to aminate the highly reactive aldehydic C-H bond. This newfound reaction allowed for the generation of previously unobtainable medium-sized heterocycles, which surprisingly provided a racemic mixture of chiral medium-sized rings. A wide array of chiral amidoporphyrins including meso-heteroatom containing porphyrins were synthesized as well during the course of research to probe their potential as new chiral ligands for the emerging field of cobalt(II)-amidoporphyrin catalyzed MRC system. A practical synthetic scheme was discovered employing the highly selective Zn(II)-bromoporphyrin synthon to generate a new library of chiral amidoporphyrin ligands for the MRC system through well-established cross-coupling methodologies.

Asymmetric nitrene transfer reactions via metalloradical catalysis (MRC) with azides has attracted research interest because of its fundamental and practical importance. The resulting nitrogen-containing units are recurrent motifs in biologically important molecules and can serve as versatile precursors in organic synthesis. The [Co(D2-Por*)] have emerged as a new class of catalysts for asymmetric aziridination and C-H amination. These metalloradical catalysts have been shown to be highly effective for the asymmetric intermolecular aziridination of a broad scope of substrates with different classes of azides with excellent to good enantioselectivity. The intramolecular C-H amination utilizing various azides can allow for the construction of diverse nitrogen containing heterocyclic compounds.

Biological systems present many challenges to researchers attempting to study them using spectroscopy. Low specificity, low sensitivity, and broad and overlapping lineshapes limit the amount of information that can be obtained in experiments. Two-dimensional fluorescence spectroscopy (2D FS) is a highly sensitive and information-rich spectroscopic technique that was developed to study the conformations and excited state dynamics of systems exhibiting exciton coupling. In this dissertation, I describe a variety of extensions of 2D FS that further increase its utility for the study of biological systems. I describe experiments on a dimer of zinc tetraphenylporphyrin embedded in a membrane, in which the signals from two conformational subpopulations were separated in order to study the thermodynamics of their interconversion. I present proof-of-principle experiments on nucleic acids that utilize fluorescence resonance energy transfer to separate signals from different subpopulations. I also describe experiments in which 2D FS was performed using ultraviolet excitation to determine the conformation of a dinucleotide of a fluorescent analogue of the nucleic acid base adenine. I discuss experiments on porphyrin dimers in which 2D FS was used as a probe of excited state dynamics. Finally, I present model calculations for a proposed variation of 2D FS in which entangled photons would be used as the excitation source. These calculations suggest that this approach has the potential to yield significantly narrower spectral lineshapes than conventional 2D FS. These experiments and calculations yield new insight into the systems investigated and establish a `toolbox' of variations of 2D FS that can be used to gain as much information as possible from experiments on challenging systems such as protein-DNA complexes. This dissertation contains previously published and unpublished co-authored material.

A produção de porfirinas por Corynebacterium diphtheriae é um objeto de estudo antigo, porém pouco explorado em Química e Ciências Médicas. O presente trabalho teve como objetivos comparar a influência de diferentes meios de cultura na produção de porfirinas por Corynebacterium diphtheriae, determinar a influencia da concentração do ferro na produção de porfirina, comparar quantitativamente a produção de porfirinas por diferentes amostras de bacilo diftérico e caracterizar químicamente os tipos de porfirinas produzidas. As técnicas utilizadas para isso foram a espectroscopia de absorção UV-visível e de fluorescência. O meio de cultura descrito por Mueller (1939), para a produção de toxina, se mostrou mais eficiente que o meio B de king, utilizado no diagnóstico laboratorial da difteria. A concentração de ferro no cultivo de Corynebacterium diphtheriae influencia a produção de porfirina. Altas concentrações de ferro inibem a produção de porfirina. A concentração de ferro onde a produção de porfirinas é máxima é de 0,20&#61549;g/mL. Dentre as 11 amostras de bacilo diftérico estudadas, a amostra HC03, fermentadora de sacarose e toxinogênica, isolada de um caso de endocardite, foi a maior produtora de porfirina. A amostra ATCC de Corynebacterium ulcerans, não fermentadora de sacarose e toxinogênica, foi a amostra que produziu menos porfirina. Todas as 11 amostras apresentaram o mesmo perfil de espectro de fluorescência, sugerindo que a porfirina produzida seja a mesma nas amostras pesquisadas. As análises feitas para a caracterização do tipo de porfirina produzida levam a crer que esta seja uma coproporfirina. Os espectros de absorção e fluorescência não permitem porém determinar o(s) isômero(s) presente(s). / Porphyrin production by Corynebacterium diphtheriae is an old research interest but less attention has been given to the subject in the areas of chemistry and medical sciences. The object of this study is to compare the influence of different culture media in the production of porphyrins by Corynebacterium diphtheriae, to determine the iron concentration influence, to compare quantitatively the production of porphyrins by different samples of diphtheria bacilli and to characterize the porphyrins identities. UV-visible absorption and fluorescence spectroscopies were chosen as analytical tools. The culture medium described by Mueller (1939), for the production of toxin, was more efficient than the medium B of King, used in the laboratory diagnosis of diphtheria. The iron concentration in the cultivation of Corynebacterium diphtheriae influence the production of porphyrin. High concentrations inhibit their production. The iron concentration for maximum production of porphyrins is 0.20 &#61549; g / mL. Among the 11 studied diphtheria bacillus, the sample HC03, fermented sucrose and toxinogenic, isolated from a case of endocarditis, was the largest producer of porphyrin. The sample of Corynebacterium ulcerans ATCC, unfermented sucrose and toxinogenic was the sample that produced less. All 11 samples showed the same profile of the fluorescence spectrum, suggesting that the porphyrin produced is the same in the samples studied. The tests made to characterize the type of porphyrin produced suggests that this is a coproporphyrin. However, the absorption and fluorescence spectra can not determine which isomer(s) is(are) present

Metal-catalyzed cyclopropanation of olefins with diazo reagents is one of the most general and efficient method to prepare cyclopropanes. The resulting cyclopropyl units are found as a basic structural element in a wide range of naturally occurring compounds and biologically active compounds, and can serve as versatile synthetic intermediates in the synthesis of multifunctionalized cycloalkanes and acyclic compounds. Since Co(II) complexes of D2-symmetric chiral amidoporphyrins [Co(D2-Por*)] were first introduced in 2004, Co(II)-metalloradical catalysis (MRC) have emerged as a new platform for asymmetric cyclopropanation. These metalloradical catalysts have been shown to be highly effective for asymmetric intermolecular cyclopropanation of a broad scope of substrates with different diazo reagents, with excellent diastereoselectivity and enantioselectivity. This dissertation aims to develop new Co(II)-MRC based enantioselective cyclopropanation systems. It will elaborate on three types of stereoselective cyclopropanation reactions from olefins: radical cyclopropanation with α-halodiazoacetates, asymmetric bicyclization of diazoketones, and radical cyclopropanation with fluoroaryl diazomethanes. These three processes will be examined in the context of diastereo- and enantiocontrol. And also, the application of cyclopropanation products have been demonstrated, which could potentially lead to more exciting works.