The prognosis for multiple myeloma (MM) and the activated B-cell subtype of diffuse large B-cell lymphoma (ABC DLBCL) is poor. Gene expression profiling studies have identified that the transcription factor, nuclear factor kappa B (NF-κB) is overexpressed and confers a poor prognosis in MM and ABC DLBCL. NF-κB regulates the transcription of genes involved in cell proliferation and survival. Thus, several groups have tried to identify and/or develop agents that target NF-κB to improve therapy and patient prognosis for MM and ABC DLBCL. Our laboratory has shown that the manganese porphyrin MnTE-2-PyP5+ inhibits NF-κB in a murine lymphoma cell culture model and enhances tumor cell death in combination with dexamethasone and cyclophosphamide, two agents that are routinely used to treat these neoplasms. MnTE-2-PyP5+ inhibits NF-κB by glutathionylating p65, a member of the NF-κB family. The objective of the following studies was to determine whether MnTE-2-PyP5+ enhances the chemotherapeutic response in human MM and ABC DLBCL cells that overexpress and depend on NF-κB for survival. The following studies demonstrate that MnTE-2-PyP5+ glutathionylates and inhibits NF-κB in human MM and ABC DLBCL cells. MnTE-2-PyP5+ also synergizes with several MM and DLBCL chemotherapeutics, including dexamethasone, cyclophosphamide, vincristine and bortezomib to enhance cell death. The data from these human cell lines will provide the basis for future studies to test MnTE-2-PyP5+ in animal models and for translating MnTE-2-PyP5+ to the clinic.

Heterometallic Cr7Ni-containing wheels have been identified as potential qubits for use in quantum information processing. The work described in this thesis details attempts to form a variety of multi-qubit systems for the purposes of better understanding the interactions occurring between the wheels and also forming potential 2-qubit quantum gates using redox/photo-active links. Mono-substituted wheels of type [Pr2NH2][Cr7MF8(O2CCMe3)15(L)], where L is acarboxylate with a pendant coordinating group, have been synthesised for use as bulky ligands in coordination chemistry with metal complexes. Various carboxylates have been substituted into the wheels and the products reacted with first row transition metal complexes in order to extend the series of linked-wheel systems. Many of these novel complexes have been characterised by X-ray crystallography, and in certain cases EPR studies have been undertaken to probe the strength of interactions occurring via different bridging units. The first well-established substituted wheel, [Pr2NH2][Cr7NiF8(O2CCMe3)15(O2CPy)] (Py= pyridine), has also been used in reactions with second and third row transition metal centres to show its ability to act as a ligand under more harsh conditions. In addition, the disubstituted product [Pr2NH2][Cr7NiF8(O2CCMe3)14(O2CPy)2] has been reacted with a copper complex in order to form a polymeric structure. Purple wheels of type [Cr7NiF3(O2CCMe3)15(EtGu)(H2O)] have been linked through a variety of extended organic molecules containing a minimum of two pendent pyridyl groups. Use of a ligand containing four pyridyl groups, 2,2´:4,4´´:4´,4´´´-quaterpyridyl(qpy) produced a three-wheel-containing system, creating an interesting modification of the wheel backbone not seen before. A series of transition metal complexes, containing qpy and its extended derivative bbpe, has been synthesised in order to form linked-wheel systems. While none of these systems has to date yielded a crystal structure, a significant amount of evidence has been collected to confirm successful formation of the desired products. UV-vis spectroscopic and electrochemical measurements show that these compounds are photo and/or redox-active,and preliminary luminescence studies indicate that the presence of the wheels quenches the emission from metal-to-ligand charge-transfer excited states. A series of mixed-wheel systems has been synthesised by reacting four different monosubstituted green wheels with four purple wheels (Cr7M, where M = Ni, Co, Mn or Zn). A total of fourteen novel systems has been formed, with two of the attempted reactions failing to occur. EPR studies on Cr7Ni-Cr7Ni linked systems show that the strongest interaction occurs when using isonicotinate as a link, with 4-pyridazinecarboxylate giving the weakest coupling. Studies have also been undertaken on Cr7Ni-Cr7Mn and Cr7Ni-Cr7Zn systems, with the former showing interactions and the latter showing none. Initial work to link wheels together indirectly via their templates was ultimately unsuccessful, but a variety of potential linker molecules were synthesised and are described.

INTRODUCTION: Reactive oxygen species are responsible for the mediation of physiologic and pathologic cellular responses. The tissue damage occurring in all inflammatory disorders, including that observed in patients with inflammatory bowel disease (IBD), is mediated by reactive oxygen species (ROS) generated and released by activated immunocompetent cells. When present in sufficient concentration, these oxidative ROS are toxic to both real or perceived infectious or allergic threats, as well as native tissues in the context of autoimmune disease. The diagnosis and interval assessment of patients with IBD currently rely on expensive and invasive procedures that create cost and logistic drawbacks for both patients and the larger health care system. Thus, there is a pressing need for the development of reliable, cost-effective, and noninvasive methods to better diagnose and manage patients with IBD. OBJECTIVES: The goal of this present study was to assess the relationship between disease activity and ambient oxidative state in the stool of patients with and without IBD. METHODS: Patients admitted to Boston Children’s Hospital (Boston, MA) were recruited and consented for participation in the study. Stool samples were collected, and the redox potential (mV) was assessed using three different redox status measuring systems. The samples were collected between November 2018 and March 2020. RESULTS: Data demonstrated that reliable measurements could be made of redox status in stool samples collected from patients with and without IBD. Data collected from patients with IBD displayed an inverse correlation between relative redox status and disease activity. CONCLUSION: The measurement of relative redox status in the stool of patients with and without IBD is a reliable tool for indicating clinical disease status. Furthermore, the initiation of an improved method for the collection and processing of stool samples from consented patients appears to increase study accrual and data collection. Data from this study can be used as the basis for future studies that assess the clinical impact of pharmacologic, lifestyle, and dietary approaches to managing fecal redox in patients with IBD.

Iron is ubiquitous in the environment, ranking fourth in abundance in the earth's crust. Iron is responsible for many environmental mechanisms including the distribution of plant nutrients and pollutants. Iron can exist in several minerals, including iron oxides. Arsenic is a naturally occurring metalloid which has been confirmed by the EPA as a carcinogen. Recently, an arsenic epidemic has unfurled in Bangladesh, poisoning an estimated 70 million people. Arsenic contamination does not exist only in the third world, but also in the United States, including Iowa. Due to the widespread distribution of arsenic and the potential for it to be leached into groundwater supplies, there has been a growing interest in establishing removal mechanisms. Atomic absorption (AA) spectroscopy and inductively coupled plasma optical emission spectrometry (ICP-OES) have been used. There has been a shift in arsenic analysis methods with the advent of more sensitive methods such as the inductively coupled plasma mass spectrometer (ICP-MS). The geology department recently acquired a Thermo Scientific XSERIES ICP-MS, so an arsenic analysis method was developed in preparation for the research conducted in this study. The ICP-MS, however, only measures total arsenic concentration. As this study focused on the oxidation state of arsenic, an alternative means for determining oxidation state was developed. As(V)-selective cartridges were used to adsorb arsenate, while letting arsenite run through. This method was checked for effectiveness and used to determine aqueous arsenic oxidation state. X-ray absorption spectroscopy (XAS) was used to determine the oxidation state of arsenic adsorbed onto the surface of iron oxide. Goethite (α-FeOOH) and magnetite (Fe3O4) are both known to strongly adsorb arsenic. In this work, the potential for As(III) oxidation and As(V) reduction by goethite was studied. As documented by Amstaetter et al., there was some evidence for adsorbed As(III) oxidation by an Fe(II)/goethite system. This study, however, also showed some evidence for oxidation of adsorbed arsenite in the presence of goethite alone. As(V) reduction by magnetite was also studied. Magnetite is capable of having different stoichiometries, or ratios of Fe(II) to Fe(III). Both an oxidized, x=0.27, and a near-stoichiometric, x=0.49, magnetite were studied for their ability to reduce arsenate. There was no evidence for As(V) reduction in the aqueous or adsorbed phase for either system.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第21593号 / 理博第4500号 / 新制||理||1646(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 林 重彦, 教授 谷村 吉隆, 教授 寺嶋 正秀 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第22548号 / 人博第951号 / 新制||人||226(附属図書館) / 2019||人博||951(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 内本 喜晴, 教授 田部 勢津久, 准教授 藤原 直樹 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

Soils contain nearly three times the amount of carbon (C) than the atmosphere, with C turnover times ranging from centuries to millennia. Although wetland soils represent a relatively small portion of the terrestrial landscape, they account for an estimated 20-30% of the global C reservoir. Seasonally flooded soils are likely the most vulnerable wetlands to climate change, as changing temperature and precipitation patterns are expected to alter the timing and duration of flooding. Seasonal variations in soil moisture are recognized as a critical control on soil C stocks and CO2emissions. However, the relative influence of associated changes in soil oxygen availability, root dynamics and the stability of mineral-organic associations are largely unknown. The overarching goal of this study was to examine the relative influence of redox state, root density and mineralogy on C cycling within seasonally flooded soil. To accomplish this goal, we combined seasonal monitoring of soil moisture, redox potential, and carbon dioxide emissions with a characterization of organic matter composition, mineralogy and root biomass along upland to lowland transects. We found that water saturation was the limiting factor for CO2emissions from seasonal flooded lowland soils, whereas soil temperature primarily regulated emissions from upland soils. Seasonal water saturation also resulted in topsoil C accumulation in lowlands compared to uplands, despite experiencing prolonged aerobic periods. Moreover, the C that accumulated in lowland topsoils was more chemically reduced compared to upland soils. However, the C chemistry in the subsoil showed the opposite trend of being more reduced in uplands compared to lowland subsoils. In sum, our results suggest that anaerobically protected soil C in seasonal flooded soils is particularly vulnerable to changing moisture regimes in response to climate change. To what extent this expected C loss is compensated by upland plant encroachment, or the neoformation of mineral-organic associations, warrants future research.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23366号 / 医博第4735号 / 新制||医||1051(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩田 想, 教授 萩原 正敏, 教授 稲垣 暢也 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22842号 / 工博第4782号 / 新制||工||1748(附属図書館) / 京都大学大学院工学研究科電気工学専攻 / (主査)教授 引原 隆士, 教授 土居 伸二, 教授 木本 恒暢 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

archives@tulane.edu / This dissertation is dedicated to the study of the synthesis, crystal structures, properties, and reactivity of heteroleptic metallodithiolene complexes of the Group 10 metals. In this work, we report a systematic survey of the reactivity of [(Ph2C2S2)2M] (M = Ni, Pd, Pt) toward ligand substitution. The upshots of the survey are the clarification of the attributes of the incoming ligand that facilitate ligand displacement, creation of a new set of heteroleptic dithiolene complexes, [M(Ph2C2S2)(C≡NR)2] (M = Ni, Pd, Pt; R = Me, Bn, Cy, tBu, 1-Adamantyl, Ph), and improvement in the efficiency by which mixed-ligand “push-pull” compounds are made. The scope of dithiolene ligand displacement by incoming ligands was expanded beyond the already reported phosphine and diimine ligands. Spectroscopic and physical characterization techniques including S K-edge X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) were used in conjunction with DFT computational methods to establish the properties of the compounds prepared in this study. Representative [(Ph2C2S2)Pt(C≡NR)2] (R = aryl) complexes exihibited low temperature luminscence in frozen solvent glasses with relatively long lifetimes. The relevance of the dithiolene redox non-innocence in the ligand substitution mechanism has also been elucidated, thereby giving an insight into the fate of the displaced dithiolene ligand. Redox disproportionation between two radical monoanionic dithiolene ligands leads to the creation of a dithione, which is an enhanced leaving group and an inherently reactive species. When displacement of dithiolene ligand from [(Ph2C2S2)2Ni] was conducted with a twofold excess of C≡NCy, 4,5-diphenyl-1,3-dithiol-2-cyclohexylimine could be isolated. The identification and characterization of this compound is consistent with the creation of dithiobenzil during the ligand substitution. The reactive α-dithione is also capable of undergoing rapid irreversible polymerization, thereby providing the thermodynamic impetus for the dithiolene ligand substitution. Chemical oxidation of [Pt(Ph2C2S2)(C≡NtBu)2] with [N(C6H4Br-4)3][SbCl6] was undertaken to form [Pt(Ph2C2SˉS‧)(C≡NtBu)2]2[SbCl6]2. Structural determination of the dication revealed appreciable shortening and lengthening of C─S and C─C bond distances, respectively, within the dithiolene ligand as compared to the charge-neutral complex, an observation which confirmed the dithiolene ligand as the locus of the redox activity in the heteroleptic monodithiolene complexes. The utility of [M(Ph2C2S2)(C≡NMe)2] (M= Ni, Pd, Pt) as synthons in their own right for heteroleptic compounds not directly attainable by ligand substitution from [M(Ph2C2S2)2] was also explored. The panorama of outcomes when [M(S2C2Ph2)(CNMe)2] (M = Ni2+, Pd2+, Pt2+) are introduced to new ligands intended to substitute for CNMe has been thoroughly defined. The most significant breakthrough was the isolation of the dicyanide complex, [Et4N]2[Ni(S2C2Ph2)(C≡N)2], which is a potentially useful precursor toward cyanide-bridged multimetallic architectures. Finally, the synthesis and structural characterization of multimetallic complexes bridged by bis(diphenylphosphine) ligands and redox active dithiolenes as end capping ligands are described. The electrochemistry study revealed that the dimetallic compounds support reversible oxidation to dications, which likely have singlet diradical - triplet states in close equilibrium. The use of dithiolene ligands as electron spin hosts offers new possibilities for the application of metallodithiolene complexes in molecule-based spintronic devices, such as quantum bits (qubits). / 1 / Antony Obanda