No description available.

A series of acene-fused porphyrins and 1,10-phenanthroline-fused porphyrins were synthesized and characterized via NMR spectroscopy and mass spectrometry. The acene-fused porphyrins exhibit unique optoelectronic properties, most notably they exhibit highly red-shifted absorption bands. The 1,10-phenanthroline-fused porphyrins are of interest for their ability to bond to as variety of metals to form chelation complexes.

Sulfonated porphyrins and phthalocyanines have been under consideration as microbicides, compounds which, when used in a topical formulation, can prevent transmission of the human immunodeficiency virus. Our studies have been directed toward the characterization of members of these classes. For the sulfonated phthalocyanines, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was helpful in determining the extent of sulfonation. We present the first report of spectroscopic characterization of a pentasulfonated phthalocyanine. Capillary electrophoresis data were sensitive to the concentration of the compounds (Chapter 1). Mass spectrometry was also very useful for establishing the extent of sulfonation in series of sulfonated porphyrins. Capillary electrophoresis was very useful in separating mixtures of these species. A study on sulfonation of a series of tetra(difluorophenyl)porphyrins showed that species with red-shifted Soret peaks were being formed. Data were consistent with an intramolecular sulfone bridge from the phenyl substituent to the porphyrin core. Sulfonation of the tetranaphthylporphyrins ring readily gave more than one sulfonic acid group per naphthyl side chain (Chapter 2). In cancer chemotherapy of solid tumors, it is desired to kill the tumor cells with minimal damage to the surrounding tissue. Brachytherapy seeds have been a considerable help in this regard for some tumors. In further developing approaches to selective tumor damage, we have evaluated a technique, Auger Electron Therapy (AET) in which one introduces a compound that is expected to bind to DNA, absorb the radiation, and then catalyze clustered DNA damage via release of a series of Auger electrons. We chose a series of metals (silver, indium, molybdenum, palladium, platinum, ruthenium, silver and zirconium) with appropriate energy levels to absorb an x-ray photon from the brachytherapy seed and used the tetracationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) as a scaffold. The amount of clustered DNA damage was quantitated by a plasmid assay. Experiments evaluated the effect of buffer, concentration of glycerol, irradiation time, and concentration of the porphyrin. No metal studied gave significant double stranded (localized) DNA damage. Significant single stranded DNA damage was observed, however, in the order zirconium >> ruthenium > palladium > platinum > silver ~ indium (Chapter 3).

The experimental cancer therapeutic agent gadolinium texaphyrin (MGd) is a cationic paramagnetic expanded porphyrin currently being tested as an X-Ray sensitizing (XRS) agent, and is a compound with demonstrated tumor localization. Additionally MGd shows promise as a chemotherapeutic agent, both as a stand-alone agent, and showing activity in vitro with ascorbate via a novel ROS generating mechanism.3 This dissertation reports the synthesis, characterization, and cell studies of novel MGdfluorophore, and platinum therapeutic conjugates. Also discussed are cationic Pt agents having cytotoxic activity. In this research we set out to answer three questions: i) can fluorescent conjugates of MGd be synthesized, with observable subcellular localization, different from that of MGd, ii) can MGd-Pt conjugates with observable Pt release be synthesized?, and iii) can Pt compounds containing a cationic moiety be tuned to have efficacy comparable to traditional Pt therapeutic agents? Two MGd-xanthene fluorophore conjugates were synthesized with the goal of using them to probe sub-cellular distribution. The anionic (FITC), and cationic (Rhodamine), fluorophore conjugates demonstrated nuclear and mitochondrial localization, respectively. In an ongoing project designed to reduce non-specific agent toxicity, a platinumreleasing MGd therapeutic conjugate was synthesized. The MGd-amidopropylmalonato-Pt conjugate demonstrated efficacy equivalent to carboplatin, a classical “non-selective” agent as inferred from in-vitro studies with A549 lung cancer cells. Aqueous stability studies of this conjugate gave results in agreement with hydrolytic loss of Pt, reversible with added Pt-diaquo. Finally, Pt complexes of amino-1-benzylpyridinium salts were synthesized and found to demonstrate significant cytotoxicity in screening studies. This latter positive development led to the suggestion that complexes of this type could consititute a new class of lipophilic-quaternary-cation Pt therapeutic agents. It is hoped that this series of putative Pt anti-cancer agents will prove useful as both stand-alone therapeutic agents and as the basis for producing conjugate with biolocalizing properties. / text

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 116-123).

The oxidation of three alkyl thioethers, phenol and 2-propanol by trans-dioxo ruthenium porphyrin species, and the synthesis, characterization and reactivity of several new ruthenium porphyrin complexes are described in this thesis. The trans-dioxo species Ru(Porp)(O)₂ [Porp= the dianions of 5,10,15,20-tetramesitylporphyrin (TMP) and 5,10,15,20-(2,6-dichlorophenyl)porphyrin (OCP)] selectively oxidize diethyl-, di-n-butyl- and decylmethyl- sulfides to the corresponding sulfoxides at room temperature. The reaction is first order in [Ru] and in [thioether]. The second order rate constants for the first O-atom transfer from the Ru(TMP) system are: 7.54xl0⁻³, 1.23xl0⁻² and 1.14x10-¹ M⁻¹ s⁻¹ respectively for the three thioethers at 20.0 °C. The activation parameters for the O-atom transfer process are also determined: for Et₂S, ∆H‡= 58.3 kJ mol⁻¹ and ∆S‡= -86 J K⁻¹ mol⁻¹; for nBu₂S, AH‡= 47.4 kJ mol⁻¹and ∆S‡= -120 J K⁻¹ mol⁻¹; for DecMeS, ∆H‡= 56.5 kJ mo⁻¹ and ∆S‡= -70 J K⁻¹ mol⁻¹. A second order rate constant of 7.23xl0⁻²M⁻¹s⁻¹ is measured at 20.0 °C for the oxidation of Et₂S by Ru(OCP)(O)₂. The intermediates Ru(TMP)(OSEt₂)₂, Ru(TMP)(OSEt₂)(OSEt₂) and the final product Ru(TMP)(0SEt₂)₂,where O and S refer to O- and S- bonded sulfoxide, are observed by ¹H nmr, and the last mentioned is isolated and characterized. A mechanism is proposed, based on electrophilic attack of the O=Ru=O moiety on :SR₂ to form bis-O-bonded species which subsequently isomerizes to bis-S-bonded species via mixed species. The Ru(TMP)(O)₂/Et₂S/O₂ system at room temperature is catalytic in complex, but produces only about 5 turnovers due to poisoning of the catalyst by the reaction product. The same system at >65 °C gives higher turnovers, but now porphyrin ligand degradation is observed, perhaps via oxidation by the O=Ru=O moiety. The Ru(OCP)(0)₂/Et₂S/O₂ system at 100 °C catalytically oxidizes Et₂S to Et₂SO and Et₂SO₂ (in ~ 4:1 ratio) and the porphyrin ligand does not undergo oxidative destruction. The Ru(TMP)(O)₂ species reacts with phenol via an observed intermediate Ru(TMP)(p-O(H)C₆H₄OH)₂ to form Ru(IV)(TMP)(OC₆H₄OH)₂, a paramagnetic (S=l) complex which is isolated and characterized. The oxidation reaction is first order in both [Ru] and [phenol] with a second order rate constant 6.90x10⁻² M⁻¹ s⁻¹at 20.0 °C. A mechanism based on electrophilic attack by the O=Ru=O moiety on the aryl ring followed by proton migration is proposed. This mechanism also explains the formation of some free para-benzoquinone and 1 equivalent of water per Ru. No ortho-benzoquinone is formed in the reaction. Preliminary ⁻H nmr studies reveal that 2-propanol is oxidized to acetone by Ru(TMP)(O)₂. A paramagnetic species (S= 1) was isolated as the only porphyrin product but not characterized. A range of novel ruthenium porphyrin complexes is also prepared. The reaction of acetylene with the four-coordinate Ru(TMP) species forms [Ru(TMP)]₂(u-C₂H₂), the first reported organometallic ruthenium porphyrin dimer. The complexes, Ru(TMP)(PhCCPh) and Ru(TMP)(PhCCH), the first π-bonded alkyne species in ruthenium porphyrin chemistry, are characterized in solution. The π-bonded alkene complexes Ru(TMP)(CH₂CH₂) OPrOH).(iPrOH) and Ru(TMP)(CH₂CH₂) are isolated and characterized, while the Ru(TMP)(cyclohexene) complex is characterized in situ. The Ru(TMP)(OSEt₂)₂ complex is isolated also by the reaction of Ru(TMP)(CH₃CN)₂with Et₂SO. The Ru(TMP)(L)₂ complexes, L= OSMe₂, OSnPr₂ and OSnBu₂ are also prepared via the above method and characterized. Some new Ru(OCP) complexes, (the monocarbonyl, the bis-acetonitrile and the dioxo- species) are also isolated and characterized. / Science, Faculty of / Chemistry, Department of / Graduate

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

This thesis concerns the construction, use and modulation of various host–guest systems, from small bispidines for binding of inorganic ions to bisporphyrin clips for supramolecular systems. Small flexible molecules undergo fast conformational movements when in solution. These conformational movements generate time-averaged population-weighted chemical shifts, coupling constants and NOEs when analysed by NMR spectroscopy. A bisporphyrin clip was designed to be used as a host for restriction of conformational movements of small flexible molecules by ditopic metal-ligand binding. Based on conformational analysis in combination with NMR analysis of molecular flexibility in solution (NAMFIS), the relative stereochemistry of flexible alditol-derived diamines containing three or four consecutive stereocentres could be determined. To further explore the idea of conformational deconvolution via host–guest binding, two flexible molecular tweezers with photoswitchable moieties were developed. Upon photoswitching cis/trans isomerisation facilitates the opening and closing of these bisporphyrin hosts. A guest molecule could then be exposed to a “catch and stretch” or “catch and release” effect. Preliminary studies have shown that photoisomerisation of the constructed systems is possible without photodecomposition and preliminary binding studies have been conducted. Controlled modulation of molecular conformations is of interest especially if the conformational steering activates a unit working as a nucleator in a larger structure or facilitates a reaction. The protonation-triggered modulation of bispidine conformations has been investigated. In addition to previously reported conformations we have observed that upon diprotonation a bispidine derivative can be driven into the unusual boat-boat conformation. Finally, the unexpected formation of persistent organic radicals with a cyclophane motif from the reaction of N,N´-diphenyl-1-5-diazacyclooctane and AgBF4 is described. Interestingly, these diradicals exhibit features such as intramolecular π-stacking without lateral displacement and also intramolecular spin pairing.