Philosophiae Doctor - PhD / Aqueous ion-intercalation batteries (AIB’s) have the potential to provide both high power for hybrid-electric transport, and low cost bulk energy storage for electric grid supply. However, a major setback to AIB development is the instability of suitable ionintercalation anode material in aqueous electrolyte. To counter this problem, the use of activated carbon (AC) (a supercapacitor anode) paired against the low cost ionintercalation cathode spinel LiMn2O4 (LMO) provides a stable alternative. This thesis comprises two novel areas of investigation concerning: (1) the development of the AC/LMO cell for high power applications, and (2) the introduction of PbSO4 as a high capacity alternative anode material paired against LMO for low cost bulk energy storage. The study on AC/LMO explores the electrode combination’s practical specific energy and power capability at high P/E (power to energy ratio) of 50:1 suitable for hybrid electric vehicle batteries. To study the relationship between electrode material loading density, active material performance, and current collector mass contribution, a specially designed cell was constructed for galvanic cycling of different thicknesses of electrode. Between a loading density range of 25 – 100 mg, ~50 mg of total active material between two 1 cm2 current collectors produced the highest 50:1 P/E ratio values of 4 Wh/kg and 200 W/kg, constituting a 4-fold reduction of the active material values of thin films at 50:1 P/E. The cycling potentials of the individual electrodes revealed that doublings of electrode film loading density increased the LMO electrode’s polarization and voltage drop to similar levels as doublings in applied current density. However, by increasing the charging voltage from 1.8 V to 2.2 V, 6 Wh/kg and 300 W/kg was obtainable with minimal loss of energy efficiency. Finally a large-format cell of a calculated 3 Ah capacity at 50:1 P/E was constructed and tested. The cell produced ~60% of the anticipated capacity due to a suspected high level of resistance in the electrode contact points. The overall conclusion to the study was that AC/LMO holds promise for high power applications, and that future use of higher rate capability forms of LMO offers a promising avenue for further research. v The second part of this thesis presents the development of a novel cell chemistry, PbSO4/LMO, that has yet to be reported elsewhere in existing literature. The cell uses aqueous pH 7, 1 M, Li2SO4 electrolyte, and forms an electrode coupling where the PbSO4 anode charge/discharge is analogous to that in Pb-acid batteries. The average discharge voltage of the cell was 1.4 V and formed a flat charge/discharge plateau. The use of a low cost carbon coating method to encapsulate PbSO4 microparticles had a marked improvement on cell performance, and compared to uncoated PbSO4 improved both rate capability and specific capacity of the material. The active materials of the carbon-coated PbSO4/LMO cell produced a specific energy 51.1 Wh/kg, which, if a 65% yield is possible for a practical cell format, equals 38.4 Wh/kg, which is 15 Wh/kg higher than AC/LMO bulk storage cells at 23 Wh/kg, but lower than Pb-acid batteries at ~25-50 Wh/kg. Interestingly, the specific capacity of PbSO4 was 76 mAh/g compared to 100 mAh/g in Pb-acid cells. The predicted cost of the cell, providing a 65% value of the active material specific energy for a practical cell can be realized, is on par with Pb-acid battery technology and, importantly, uses 2.3 × less Pb/kWh. The cycling stability achieved thus far is promising, but will require testing over comparable cycle life periods to commercial batteries, which could be anywhere between 5 – 15 years.

Bile acid-based cation sensors involving through space photo-induced electron transfer (PET) processes have been synthesized. In this approach, appropriate known fluorophores and aza crown ether receptor units were attached on a suitable bile acid scaffold. A through space photo induced electron transfer from N-atom of the aza 18-crown-6 to the excited pyrene was responsible for quenching of the pyrene fluorescence. A fluorescence enhancement was observed with the addition of K+ due to the inhibition of fluorescence quenching by PET mechanism. In order check the relationship between the sensitivity and the molecular structure of the sensors, four different molecules with different geometries were synthesized. The changes in the fluorescence spectra for different sensors were recorded in MeOH. The binding constants calculated by curve fitting showed that while the binding constants did not significantly vary, the sensitivities were different depending on the structure of the sensors. The modular nature of the sensor design was verified by changing the receptor module from aza-18-crown-6 to aza-15-crown-5, keeping other parts of the sensor same, to prepare a sodium selective sensor using the same principle. Fluorescence titration in MeOH confirmed the Na+ selective sensing in the presence of K+. The modular design concept was further extended by replacing the fluorophore pyrene to a coumarin derivative. Coumarin sensors showed a behavior similar to that of the pyrene sensors. In order to check the possibility of sensing metal ions in water, non ionic surfactant, Triton X-100 was chosen to dissolve the sensor in water. Fluorescence titration of the sensors showed a desired selective fluorescence enhancement with the particular metal ions. Merrifield resin and water swellable Tentagel® was used to immobilize the sensor to fabricate reusable sensor beads for detecting the metal ions in non polar solvent and water respectively. Fluorescence enhancements of the sensor beads with the metal ions confirmed the process in the immobilized solid state. K+ and Na+ selective sensor beads successfully demonstrated the fluorescence enhancement with the respective cations. This general strategy can be extended to fabricate other sensors for practical uses.

Click chemistry is a molecular synthesis strategy based on reliable, highly selective reactions with thermodynamic driving forces typically in excess of 20 kcal mol-1. The 1,3-dipolar cycloaddition of azides and alkynes developed by Rolf Huisgen saw dramatic rate acceleration using Cu(I) as a catalyst in 2002 reports by Barry Sharpless and Morten Meldal enabling its click chemistry eligibility. Since these seminal reports, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has become the quintessential click reaction finding diverse utility. The popularity of the CuAAC has naturally led to interest in new catalyst systems with improved efficiency, robustness, and reusability with particular focus on nanomaterial catalysts, a common trend across the field of catalysis. The high surface area of nanomaterials lends to their efficacy as colloidal and heterogeneous nanocatalysts, but the latter boasts the added benefit of easy separation and recyclability. With any heterogeneous catalyst, a common question arises as to whether the active catalyst species is truly heterogeneous or rather homogeneous through metal ion leaching. Differentiating these processes is critical, as the latter would result in reduced efficiency, higher cost, and inevitable environmental and heath side effects. This thesis explores the CuAAC from an interdisciplary approach. First as a synthetic tool, applying CuAAC-formed triazoles as functional, modular building blocks in the synthesis of optical cation sensors by combining azide and alkyne modified components to create a series of sensors selective for different metal cations. Next, single-molecule spectroscopy techniques are employed to observe the CuNP-catalyzed CuAAC in real time. Combining bench-top techniques with single-molecule microscopy to monitor single-catalytically generated products proves to be an effective method to establish catalysis occurs directly at the surface of copper nanoparticles, ruling out catalysis by ions leached into solution. This methodology is extended to mapping the catalytic activity of a commercial heterogeneous catalyst by applying super-localization analysis of single-catalytic events. The approach detailed herein is a general one that can be applied to any catalytic system through the development of appropriate probes. This thesis demonstrates single-molecule microscopy as an accessible, effective, and unparalleled tool for exploring the catalytic activity of nanomaterials by monitoring single-catalytic events as they occur.

Im Mittelpunkt dieser Arbeit steht die Untersuchung des Typ III-Sekretionssystem (T3SS) bei Bradyrhizobium japonicum USDA110. Im ersten Teil der Arbeit wird die Regulation der Gene des Typ III-Sekretionssystems in B. japonicum beschrieben. Dabei wurde die tts-Box, als neuartige Promotorsequenz für die Gene des T3SS und sekretierter Proteine charakterisiert. Mittels Expressionsanalysen konnte die Aktivität von 34 Genregionen downstream der tts-Boxen in Abhängigkeit von Flavonoiden gezeigt werden. Auch in Symbiose, in frühen Infektionsstadien und in reifen Knöllchen von verschiedenen Wirtspflanzen wurde die Expression ausgewählter Gene nachgewiesen. Der zweite Teil der Arbeit widmet sich der Analyse der sekretierten Proteine von B. japonicum. Über 100 Proteine wurden im Überstand von Kulturen nachgewiesen, wovon 68 Proteine durch Massenspektrometrie identifiziert werden konnten. Zusätzlich wurden 12 Proteine identifiziert, die in Abhängigkeit des T3SS sekretiert werden. Im dritten Teil der Arbeit wurden die sekretierten Proteine NopE1 und NopE2 näher untersucht und als bona-fide Effektoren nachgewiesen. Die rekombinant produzierten Effektoren NopE1 und NopE2 wurden biochemisch charakterisiert. Für die Domäne unbekannter Funktion (DUF1521) wurde eine spezifische Selbstspaltungsaktivität in Gegenwart von Calcium gezeigt. Nachweislich ist diese Aktivität relevant für die Symbiose. Somit konnte der Proteindomäne mit bisher unbekannter Funktion eine biochemische Funktion zugeordnet werden. Im letzten Teil der Arbeit wurden die Untersuchungen an dieser Domäne auf weitere Proteine ausgedehnt. Für das putative Effektorprotein VIC_001052 aus V. coralliilyticus, dem Verursacher der Korallenbleiche bei Pocilla damicornis, wurde ebenfalls die in vitro Calcium-induzierte Selbstspaltungsaktivität gezeigt. Aufgrund der konservierten Selbstspaltungsfunktion wurde die DUF1521-Domäne in metal-ion inducible autocleavage- (MIIA)- Domäne umbenannt.:I. Einleitung Rhizobien-Leguminosen-Interaktion Proteinsekretionssysteme II. Zusammenfassung der Forschungsergebnisse 1. Untersuchung der Expression des Typ III-Sekretionssystems in Knöllchen und Analyse des tts-Box-Promotors 2. Identifizierung sekretierter Proteine von Bradyrhizobium japonicum 3. Untersuchung der sekretierten Proteine NopE1 und NopE2 4. Untersuchung von konservierten MIIA-Domänen III. Diskussion IV. Zusammenfassung V. Literaturverzeichnis VI. Anhang VII. Publikationen

Lanthanide(III) complexes of DOTA derivatives are utilized in the medical imaging techniques such as magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance spectroscopy (MRS), nuclear imaging (PET and SPECT), or optical methods (luminescence). It has been shown that relaxometric parameters of the Gd(III) complexes of DOTA derivatives with a phosphinic acid pendant arm (Gd-DO3APR ) can reach optimal values (e.g. water residence time, τM, being close to ~10 ns). The relaxometric parameters can be further modified through the phosphorus substituents. It is also known that the complexes possess a high thermodynamic stability and they are kinetically inert. The main goal of this Thesis is an investigation of the effect of pendant amino group protonation in substituents bound to the phosphorus atom on properties of the complexes. Thus in this Thesis, DOTA derivatives with the phosphinic acid pendant arm with an amino group and their complexes were prepared and characterized. The complexes are intended as contrast agents for molecular imaging techniques (mainly for MRI and 31 P MRS). The first part of the Thesis introduces two new versatile "phospha-Mannich" protocols performed under mild conditions. Amino-H-phosphinic acids (AHPAs) were synthesized with excess of...

<p>In the past few decades, invasive mycosis has become a growing threat to global health, afflicting millions of people and claiming the lives of more than 1.5 million patients every year. Moreover, the economic burden of mycotic infections has become increasingly exhausting especially with the recent increases in the number of the high-risk population, the immunocompromised individuals. In the USA, the cost incurred by mycotic infections was estimated to be of more than $7.2 billion only in 2017. Of particular concern, <i>Candida</i> species are the most common fungal pathogens that infect humans, resulting in considerable morbidities and mortality rates that often exceed 50%. Unfortunately, the antifungal drug discovery is currently unable to keep pace with the urgent demand for more effective therapeutic options. Further complicating the situation is the recent emergence of multidrug-resistant species such as <i>Candida</i> <i>auris</i>, triggering outbreaks of deadly Candidemia across the globe. Given the risks inherent to the traditional de-novo drug discovery, combinatorial therapeutics stands out as a promising tool to hamper drug resistance and extend the clinical utility of the existing drugs. In this study, we assembled and screened ~3147 FDA-approved drugs and clinical molecules against fluconazole-resistant <i>C. albicans</i> and <i>C. auris</i> isolates, for the aim of restoring the antifungal activity of azole antifungals against drug-resistant <i>Candida </i>species. The screen revealed five promising hits: pitavastatin (antihyperlipidemic), ospemifene (estrogen receptor modulator), sulfa antibacterial drugs, lopinavir (antiviral), and aprepitant (antiemetic).</p> <p>All identified hits demonstrated variable azole chemosensitizing activities depending on the tested <i>Candida</i> species and the azole drug. Pitavastatin displayed broad-spectrum synergistic interactions with both fluconazole and voriconazole against isolates of <i>C. albicans</i>, <i>C. glabrata</i>, and <i>C. auris</i>. Ospemifene was able to interact synergistically with itraconazole against multiple fungal isolates including <i>Candida</i>, <i>Cryptococcus</i>, and <i>Aspergillus</i> species. Sulfa drugs displayed potent synergistic activities with different azoles against <i>C. albicans</i>, however, a limited efficacy was observed against efflux-hyperactive isolates such as <i>C. auris</i>. On the other hand, both lopinavir and aprepitant exerted potent and broad-spectrum synergistic activities with itraconazole and were effective against multiple <i>Candida</i> species including <i>C. albicans</i>, <i>C. auris</i>, <i>C. glabrata</i>, <i>C. krusie</i>, <i>C. tropicalis</i>, and <i>C. parapsilosis</i>. Furthermore, using <i>Caenorhabditis elegans</i> as an infection model, all drug combinations significantly reduced the fungal burden in the infected nematodes and significantly prolonged their survival as compared to single-drug treatments. Multiple phenotypic and molecular assays indicted that the identified hit compounds use distinct mechanisms to enhance the antifungal activity of azole drugs. These mechanisms include efflux pump inhibition, interference with the folate biosynthesis and disturbance of iron homeostasis. Taken together, this study reveals novel and potent azole chemosensitizing agents effective against multiple azole-resistant isolates and opens the door for more investigations to assess their clinical potential in human medicine as promising antifungal adjuvants.</p>

Des méthodes électrochimiques à potentiel et à courant imposé appliquées à l'étude des réactions avec dépôt métallique sur un métal de même nature ou sur un substrat étranger sont examinées. Des précisions inédites concernant la voltamétrie à escalier de potentiel et la voltamétrie à signaux carrés de potentiel pour les réactions rapides et lentes avec et sans nucléation tridimensionnelle sont apportées. Les conclusions théoriques sont validées par l'étude du couple Ag(I)/Ag sur les électrodes d'or et d'argent dans HNO3 1 M, KNO3 1 M et dans le liquide ionique [EMIM][NTf2] anhydre ou humide. Le dépôt d'argent s'effectue sans aucune surtension de nucléation tridimensionnelle seulement dans HNO3 et dans [EMIM][NTf2] anhydre. La réaction électrochimique est rapide dans les solutions aqueuses et dans [EMIM][NTf2] humide tandis qu'elle est lente dans [EMIM][NTf2] anhydre. Les paramètres cinétiques sont déterminés par simulation numérique. / Electrochemical methods with potential or current imposing for the study of reactions with metal deposition on the same metal and on foreign substrate are reviewed. New information is provided on staircase voltammetry and square wave voltammetry for fast and slow electrode reactions with and without three-dimensional nucleation. Theory is validated through the study of Ag(I)/Ag couple on gold and silver electrodes in 1 M HNO3, 1 M KNO3 and in dry or wet [EMIM][NTf2] ionic liquid. Silver deposition takes place without any three-dimensional nucleation overvoltage only in HNO3 and in dry [EMIM][NTf2]. The electrochemical reaction is fast in aqueous solutions and in wet [EMIM][NTf2] while it is slow in dry [EMIM][NTf2]. Kinetic parameters are determined by numerical simulation.

Renewable lignocellulosic materials are promising green plastic alternatives to fossil fuel-based plastics. However, the hydrophilic nature and poor water resistance of lignocellulosic materials have hindered their practical applications. This study reports a facile metal-ion-modification (MIM) route, swelling with aqueous metal ion solutions, and drying to convert conventional hydrophilic paper and wood pulp into biodegradable hydrophobic paper and tableware without the addition of hydrophobic sizing chemicals/materials. Metal ions such as Fe3+ and Zr4+ can coordinate with pulp fibers’ polar groups (i.e., O.H., C=O, and COOH) that induce self-assembly of their surface fibrillated “hairy” cellulose nanofibrils to form a more compact structure with fewer available O.H. groups for water sorption. The formation of coordination bonds with polar groups (i.e., O.H., C=O, and COOH) decreases the surface energy of pulp fibers and increases their hydrophobicity and water resistance. Only ~3 mg of metal ions is needed to induce the wettability transition in 1 g of kraft pulp, resulting in hydrophobic paper and tableware with water contact angles (WCAs) of 120-140° and displayed wet tensile strengths of up to 9.5 MPa, and low water absorbency, which were comparable to synthetic polymer films. This MIM technique can be integrated into the existing paper-making process for the scalable production of hydrophobic papers and tableware, providing an alternative route for developing sustainable and biodegradable plastic counterparts. The MIM-induced lignocellulose hydrophobization mechanisms were elucidated using X-ray photoelectron spectroscopy (XPS), Fourier transforms infrared spectroscopy (FT-IR), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), and density functional theory (DFT). Furthermore, this MIM technique was also evaluated for its applicability in wood treatment. The treatment effectively tunes the wood surface from hydrophilic to hydrophobic, enhancing its water resistance. The MIM treatment significantly improved the dimensional stability of SYP, red oak, and poplar. For example, the Fe3+ treatment reduced the tangential swelling of SYP, poplar, and red oak by 57%, 50%, and 40%, respectively. Overall, this eco-friendly and facile MIM method holds promise for developing sustainable and biodegradable alternatives to conventional plastics, contributing to a more environmentally friendly future.

In this work, hydrophilic fluorene-based derivatives that contain ethylene oxide substituents, have been synthesized and characterized for potential use as new fluorophores for bioimaging applications and for fluorescence sensing of heavy metals. Symmetrical and unsymmetrical fluorene derivatives based on structural types of acceptor-pi-acceptor, acceptor-pi-donor, and donor-pi-donor were characterized by TGA, UV-vis absorption, fluorescence emission, lifetime, anisotropy, and two-photon absorption (2PA) cross section. They were found to possess high thermal stability, high photostability, high fluorescence quantum yields, and generally large two-photon absorption cross sections, making them quite suitable for new probes in single-photon absorption and two-photon absorption fluorescence microscopy imaging. Novel hydrophilic fluorene derivatives were synthesized from fluorene in multiple steps employing the metal-catalyzed Heck coupling reaction, the Stille reaction, the Sonogashira reaction, the Ullmann condensation reaction, and "click" chemistry. To increase the hydrophilicity of the new compounds, ethylene oxide substituents were utilized for to impart water solubility. An alternative alkylation methodology using ethyleneoxy tosylates was introduced for the synthesis of ethylene oxide-containing fluorene derivatives. Several of these hydrophilic derivatives were incubated into various cell lines as new probes for both conventional and two-photon absorption fluorescence bioimaging. These compounds were biocompatible, exhibiting low cytotoxicity as determined by cell viability studies, and displayed colocalization for selected cellular organelles. In addition, hydrophilic bis(1,2,3-triazolyl)fluorene derivatives were found to exhibit sensitive fluorescence responses in the presence of certain heavy metal, and were selective for sensing zinc and mercury over other a number of other metal ions relevant to living cells or other biological environments. The UV-vis absorption and fluorescence emission spectra of the complexes exhibited a blue-shifted absorption and emission for selective metal chelation upon binding to zinc and mercury(II) ions, resulting in an approximately two-fold enhanced fluorescence response. Fluorescence titration studies revealed that the complexes of 1:2 and 1:3 ligand to metal formed with binding constant values of 108 and 1014 for zinc and mercury ions, respectively. Finally, preliminary experiments were performed to explore the possibility of employing select hydrophilic fluorene-based derivatives in the synthesis of hydrophilic fluorescent gold nanoparticles. Although results are very preliminary, the aim is to use such materials for other biomedical applications, such as surface enhanced scattering resonance and noninvasive photothermal therapy to diagnose and to treat cancers. Thus, this research had led to the discovery of alternative methodologies for synthesis of hydrophilic fluorene derivatives by alkylation with alkyl tosylates and synthesis of hydrophilic fluorescent molecule capped gold nanoparticles. Furthermore, several novel hydrophilic fluorene-based derivatives were synthesized and characterized for their linear and nonlinear photophysical properties, and are now available for further examination of their bioimaging and sensing applications.

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